2021 MMCRI-Year-in-Review

21Year in ReviewMAINE MEDICAL CENTER RESEARCH INSTITUTE mmcri.org

TABLE OF CONTENTS Message from the Director.............................................................................................. 2 MMCRI at a Glance...................................................................................................... 3-4 Noteworthy................................................................................................................5-10 Research Highlights: ................................................................................................ 11-32 COVID-19 Research ........................................................................................... 12-18 Population & Health Services Research..............................................................19-20 Basic & Translational Research .........................................................................21-24 Clinical Research & Clinical Trials ..................................................................... 25-32 Research Training & Career Development................................................................. 33-36 Looking Forward: The Future of Research within MaineHealth and Beyond ................ 37-38 Cover photos: Staff: Top Left: MMCRI’s Engagement Council organized baked good donations for hospital staff. Members pictured: Larisa Ryzhova, Phuong Le, Anne Harrington, and Leah Seften. Top Right: 2021 Summer Student Research Program Students that worked in research laboratories in the Center for Molecular Medicine. Ribbon cutting for MMCRI’s mass spectrometer instrumentation. L to R: Dr. Cal Vary (Faculty Scientist), Dr. Elizabeth Jacobs (VP Research), and Dr. Doug Sawyer (Chief Academic Officer). Autumn at the Research Institute. Bottom Left: Rebecca Condruti, Graduate Student in the Reagan Lab. Photo credit: Peter Gumaskas. Science images: Front Cover: Left: Large bone cell (green osteoclast) with proteins that detect signals from the nervous system (red adrenergic receptors). Image from the Motyl Lab. Right: Myeloma tumor cells express CD38, a protein that helps the cells home to the bone marrow. The localization of that protein primarily in the cell membrane, shown in red. The tumor cells appear green due to expression of green fluorescent protein (GFP) and their nuclei are stained blue with DAPI. Image from the Reagan Lab in which targeting CD38 is an area of research. Back Cover: Primary bone marrow fat cells (adipocytes) isolated directly from human donors grown in 3 dimensional culture using silk scaffolds for the first time. Fat cells store lipids and triglycerides which are shown in red (oil red-o neutral lipid stain), with cellular actin filaments shown in green (phalloidin). Silk scaffold also in green; image generated with confocal laser microscopy. Image from the Reagan Lab.

Message from the Director Dear Colleagues and Supporters, I am excited to share Maine Medical Center Research Institute’s 2021 Year in Review with you, highlighting the many notable accomplishments and stories of the diverse work occurring at the Institute. This review also marks the first full year I have been Vice President for Research, offering me a moment to pause and celebrate all the remarkable research that occurs throughout MaineHealth and the people who make it happen — from the principal investigators to the leaders and staff who make sure we conduct high quality, ethical, and funded research. We continue a very positive trajectory of funding growth, including several notable awards focused on improving the care and health of the people of Maine. They include several awards through the Northern New England Clinical and Translational Research Network (NNE-CTR) to understand how best to overcome COVID-19 vaccine hesitancy in rural communities in Maine, how to provide accessible COVID-19 testing among populations who are at high-risk for COVID and its complications, and, in collaboration with the Passamaquoddy Tribe, to study the impact of poor water quality on Tribal Members’ health and well-being. We also are part of a large National Institutes of Health (NIH) multi-site study, known as RECOVER, to understand the long-term effect of COVID, often referred to as “long COVID” (page 13). Additionally, we received a large research infrastructure building grant, the Center of Biomedical Research Excellence (COBRE) in Acute Care Research and Rural Disparities award that is focused on improving acute care and reducing health disparities in our state (page 25). Several investigators also received grants and awards marking important milestones in their careers. The grants include a career development award from the Tufts Center for Translational Science to Eric Anderson, PhD, to study Maine cancer patients’ experience with and expectations of genetic tumor testing, NIH R01 awards to Aaron Brown, PhD, and Katy Motyl, PhD, marking their transition to independence as investigators (page 21 & 22), and a Transformative Research Award from the NIH for Joe Nadeau, PhD, as a Principal Investigator (page 23). One of our scientists also received a significant recognition from Tufts. Lucy Liaw, PhD, received the Milton O. and Natalie V. Zucker Prize for lifetime scientific achievement (page 7). These are just the highlights! There is so much more contained in this year in review. We hope this review will provide you with insight into the breadth and depth of our activities. I hope you will also check out a new section, “Looking Forward: The Future of Research within MaineHealth and Beyond” so you can understand our vision for the next year and beyond (page 37). Thank you for your continued support of and enthusiasm for our work. I look forward to another amazing year of research at MaineHealth. Sincerely, Elizabeth Jacobs, MD Vice President of Research Maine Medical Center Research Institute

LEADERSHIP TRANSITION MMCRI At A Glance In August Tom Gridley, PhD, stepped down from his position as Director of the Center for Molecular Medicine in order to focus on his expanding leadership roles in the Northern New England Clinical and Translational Research Network (NNE-CTR) and the Center of Biomedical Research Excellence (COBRE) in Acute Care Research and Rural Disparities. Rob Koza, PhD, is currently serving as Interim Director until a replacement is identified. Dr. Gridley has made significant contributions to Maine Medical Center Research Institute since his arrival in 2011. As a researcher, Dr. Gridley is best known for his critical contributions to understanding the complex role the Notch signaling pathway plays in developmental processes during embryogenesis and organogenesis, and how disruptions in Notch signaling can lead to birth defects. He is one of the founders of the field, and is well-known and respected internationally. Dr. Gridley has served as mentor to more than 15 Principal Investigators and guided diverse areas of research including cancer, fat metabolism, and bone metabolism and disease. Dr. Gridley currently serves as Vice Chair of the MaineHealth Institutional Review Board, and is a member of the MaineHealth Intellectual Property Committee and the MaineHealth Precision Medicine Council. We are grateful to Dr. Gridley for his leadership of the Center for Molecular Medicine, and will continue to appreciate his contributions to MMCRI. INSTITUTIONAL WORK ON DIVERSITY, EQUITY, AND INCLUSION The MMCRI Diversity, Equity and Inclusion Workgroup, formed in 2020, is committed to creating an equitable, inclusive environment that is welcoming to diverse staff, scientists, and collaborators. The group is led by Elizabeth Scharnetzki, PhD, Staff Scientist and Cole Ferm, Research Program Manager. The group comes together to examine how systemic inequities, in particular systemic racism, impact diversity in our professional spheres, in the biomedical and health services research questions we ask, and how we engage with our communities to carry out our research and communicate our findings. This year, our group has held 20 meetings, consisting of didactic sessions led by twelve national experts and individuals with lived experience. Some of our speakers this year have included Dr. Winfred Williams, Deputy Editor at the New England Journal of Medicine, who came to speak to the group about promoting diverse inclusion in clinical trials, and Dr. Tamarra- James Todd, an Associate Professor of Environmental Reproductive Epidemiology at Harvard Chan School of Public Health, who spoke to our group about the use of race in statistical models. Notably, the MMCRI DEI Workgroup was invited to give a talk at the National Postdoc Association’s annual conference about our anti-racist curriculum and workgroup model. In addition to our education sessions, the MMCRI DEI group has championed several important institutional initiatives, including revisions to our interview process and protected time for community service. 3 MAINE MEDICAL CENTER RESEARCH INSTITUTE: 2021 YEAR IN REVIEW

2021 Leadership 2021 Fast Facts Executive Administration 274 Staff Members $22M Elizabeth Jacobs, MD Total 2021 Grant Funds Vice President of Research, MMCRI 43 275+ New Grants Awarded Kneka Smith, EdD, MPH Oncology, Vice President of Operations, Neurology, Clinical Trial Studies Academic Affairs & Cardiology Top 3 Clinical Research Areas Research Center Leadership 319 Scientific Publications Thomas Gridley, PhD (January-August 2021) 12 Robert Koza, PhD (current, Interim) Core Facilities with State-of-the- Art Director, Center for Molecular 86 Equipment and BioBank Tissue Medicine Repository, which distributed over 2 2,798 biospecimens Elizabeth Jacobs, MD Interim Director, Center for Outcomes Learners & Trainees in MMCRI’s Research & Evaluation Education & Training Program Clifford Rosen, MD Patents issued in 2021 for Mab HU177 & Director, Center for Clinical & Mab XL313, antibodies that enhance the Translational Research anti-tumor activity of immune checkpoint inhibitors; Peter Brooks PhD, Faculty Susan Santangelo, ScD Scientist; Jennifer Caron, Research Director, Center for Psychiatric Associate; and Liangru Contois, former Research Staff Scientist in the Brooks Lab. 2021 Sources of Research 12.4%: Support by Sponsor Type Industry 12.4%: Foundation & Nonprofit 75.2%: Federal MaineHealth makes research a priority and also has generously provided support to MMCRI’s operating budget. 2021 MH Operating Subsidy $10.4M 4 2021 YEAR IN REVIEW

NOTEWORTHY NORTHERN NEW ENGLAND CLINICAL AND TRANSLATIONAL RESEARCH NETWORK CONTINUES TO BUILD PATIENT-CENTERED RESEARCH INITIATIVES The aging and rural populations of northern New England Cliff Rosen, MD suffer from numerous chronic health issues, including cancer, obesity, diabetes, cardiovascular disease, and substance abuse. In 2017 MMCRI received $20M from the National Institutes of Health (NIH) to establish the NNE-CTR, to launch an initiative to address these issues and expand clinical and translation research throughout the tri-state region. Comprised of MaineHealth, the University of Vermont, and the University of Southern Maine, the NNE-CTR’s mission is to enhance the health of people in northern New England (ME, NH, VT), by fostering and coordinating clinical, translational, and educational research activities. Leading the NNE-CTR is Clifford Rosen MD, Director of the Center for Clinical and Translational Research at MMCRI, and Gary Stein PhD, Chair of the Department of Biochemistry at the University of Vermont Larner College of Medicine. In its first four years the NNE-CTR has made tremendous progress. It has helped generate additional Gary Stein, PhD grant support to MaineHealth in oncology research and other areas, has funded 29 pilot research projects including cardiac health in rural regions, COVID-19 challenges, opioid addiction, and health issues faced by the elderly, and, established a tele-mentoring program to benefit rural patients via pilot project support. Importantly, the NNE-CTR has strengthened commitments to underserved communities, including New American and Native American populations and rural populations. The NNE-CTR has begun to develop a novel rural communication network of health care sites, supported an analysis of food insecurity and its impact on rural populations, are working with the Passamaquoddy Tribe on a public health issue and have begun to set up Community Engagement Councils in rural areas. 2021 Brings Additional Focus to COVID-19 This year there were three COVID-19 initiatives supported by the NNE-CTR. A project addressing vaccine hesitancy in rural Maine is led by Kathleen Fairfield, MD, DrPH, and Elizabeth Jacobs, MD, MAPP, both of whom received a pilot grant award from the NNE-CTR. In addition, both Drs. Fairfield and Jacobs are leading another effort as part of the NIH’s Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) program, to expand clinical research in the region and address the needs of underserved populations. On a national level, Dr. Rosen chairs the governance committee for the National COVID Cohort Collaborative (N3C, a registry to share clinical data on COVID-19 nationally) and is a Principal Investigator for the CTR consortium of the NIH-sponsored “Researching COVID to Enhance Recovery” (RECOVER) initiative, a nationwide study of the long-term effects of COVID-19. For more details on these projects see the COVID-19 research section on page 12 and look for the NNE-CTR logo throughout for additional projects from the research network. For more information on the NNE-CTR visit: nne-ctr.net 5 MAINE MEDICAL CENTER RESEARCH INSTITUTE

CULTIVATING THE NEXT GENERATION JUNIOR FACULTY MaineHealth supports the next generation of healthcare professionals, biomedical scientists, and health services researchers to improve the health of our communities. Maine Medical Center Research Institute committed in 2021 to updating faculty and non-faculty positions as well as expanding ladders for professional growth to encourage progression and innovation. Several early career investigators transitioned to Faculty Scientist positions due to their scientific achievements, and one has joined the organization as a new hire. Congratulations to these promising investigators. Isha Agarwal, MD, PhD, is an epidemiologist and emergency medicine physician, working in the Maine Medical Center Emergency Department as an attending physician. In August, she joined the Center for Outcomes Research & Evaluation as a Faculty Scientist I. Dr. Agarwal is interested in how the work environment of emergency physicians impacts their clinical practice and mental and physical health. In January Eric Anderson, PhD, transitioned to a Faculty Scientist I position in the Center for Outcomes Research & Evaluation. Dr. Anderson investigates the psychological aspects of health and medical care. His current research explores patients’ understanding, hopes, and decision making for complex medical care, such as genomic tumor testing for patients with cancer. Matthew Lynes, PhD, joined the Center for Molecular Medicine as a Faculty Scientist I in August. He comes to MMCRI from his previous position as an Assistant Investigator at Joslin Diabetes Center and Instructor in Medicine at Harvard Medical School. His research interests include obesity, and how an imbalance in energy intake and energy expenditure leads to metabolic disease. He will be a part of our Center for Biomedical Research Excellence in Metabolic Networks. Jenny Carwile, ScD, MPH is an environmental epidemiologist in the Center for Outcomes Research & Evaluation. Dr. Carwile transitioned to a Faculty Scientist I position in July. Her research focuses on the interplay between diet and exposure to environmental chemicals, particularly in children. Her current project examines exposure to arsenic and other chemicals in private well water in Maine. 2021 YEAR IN REVIEW 6

NOTEWORTHY ACCOLADES & AWARDS: Lucy Liaw, PhD, Awarded Zucker Prize Lucy Liaw, PhD, Faculty Scientist and Director of Research Training and Education Programs at MMCRI, was awarded the Milton O. and Natalie V. Zucker Prize in July. The Zucker Prize is awarded annually to a woman scientist on the Tufts University School of Medicine faculty for outstanding career achievements in research. Dr. Liaw has made substantial scientific contributions over her long career, many in the field of vascular biology. In addition, she has made significant contributions as a team scientist and educator. Her excellence and generosity as a collaborator and educator are well-known and have advanced science in Maine and at Tufts University School of Medicine beyond her significant individual contributions. Matthew Siegel, MD, Appointed to Federal Board Overseeing National Policy on Autism Spectrum Disorder Research In July, the U.S. Department of Health and Human Services (HHS) announced the selection of a physician leader from Maine Behavioral Healthcare and MMCRI to serve on the board of the Interagency Autism Coordinating Committee, overseeing the federal government’s work in support of those impacted by autism spectrum disorders. Matthew Siegel, MD, Vice President of Medical Affairs, Autism and Developmental Disorders Service at Maine Behavioral Healthcare and Faculty Scientist at MMCRI, is one of 22 individuals, and only 4 scientists, from across the country named to serve on the coordinating committee. This committee formulates advice and recommendations for the HHS Secretary on matters related to autism research, services, and policy. Dr. Siegel recently led the development of the Glickman Lauder Center of Excellence in Autism and Developmental Disorders and is also a principal investigator of the Autism and Developmental Disorders Inpatient Research Collaborative, a network of specialized child psychiatry units performing studies of children severely affected by autism and intellectual disability. He has also authored the current practice guidelines for treatment of autism and of intellectual disability for the American Academy of Child and Adolescent Psychiatry. “I am thrilled to have this opportunity to engage with our partners at the federal level,” said Dr. Siegel of his new appointment. “Supporting those with autism and related disorders requires a comprehensive approach, and this committee provides key guidance for the focus of research and services across the country.” Lambrew Research Retreat Showcases Science & Discovery Another successful Costas T. Lambrew Research Retreat took place on May 5-6, 2021. The virtual two-day event kicked off with keynote speaker Vivek Kumar, PhD, Assistant Professor at The Jackson Laboratory. Dr. Kumar presented on genetic approaches to modeling addiction in laboratory models. Other retreat highlights included oral presentations by trainees and faculty of award-winning abstracts, chosen from over 70 submissions in the areas of basic/translational research, clinical/population health, quality improvement, and health professions education. Day two included small group rapid virtual poster presentations featuring 60 posters presented by faculty, staff, and trainees from institutions across MaineHealth, UMaine, and the University of Southern Maine. Topics ranged from cardiovascular biology and metabolic health to behavioral health, population health, COVID-19, and more. Each session was facilitated by 2-3 clinicians and/or researchers from MaineHealth institutions. For more information: mmcri.org/lambrewretreat 7 MAINE MEDICAL CENTER RESEARCH INSTITUTE

ACKNOWLEDGEMENTS Thank you to the individuals and organizations for helping us make 2021 a year of growth and discovery for Maine Medical Center Research Institute. With your support and partnership we will achieve even greater things in the years ahead. Private Foundations and Federal Funders Individuals Institutes Health Resources and Services Ms. Rebecca L. Allisot Administration Rea V. Anunciado Koza, M.D. 340B Health Fund National Institutes of Health Mr. Joseph E. Athanas American Heart Association United States Department of the Army Ms. Trina J. Austin American Thrombosis and United States Department of Veterans Affairs Mr. Jeffrey Baer Ms. Tammy L. Batchelder Hemostasis Network State of Maine Mrs. Laura K. Bennett Brain and Behavior Research Foundation Mr. John Benoit (collaborative with Tufts) Maine Outdoor Heritage Fund Ms. Susan J. Bernier Bristol-Myers Squibb Foundation Maine Center for Disease Control Pauline Bill Trust Cambia Foundation Sojourn State of Maine Department of Mrs. Julie L. Blake Health and Human Services Ms. Samantha M. Blau Scholars Program Ms. Margaret Bodington Cystic Fibrosis Foundation Corporate/Industry Funders Ms. Nancy J. Boisvert Harold Alfond Foundation (in collaboration Mrs. Debra A. Bourgoin Cross Insurance Dr. Jordan L. Bundy with The Jackson Laboratory) IDEXX Mr. Chad J. Burnham Hinda and Arthur Marcus Institute for Aging Medical Mutual Insurance Company of Maine Ms. Debra D. Burris Medtronic Jennifer C. Campbell, PT research at Hebrew Rehabilitation Center Oncopeptides Ms. Amy B. Caron Hitchcock Foundation Smith & Nephew, Inc. Mrs. Jennifer M. Caron Intersocietal Accreditation Commission Spectrum Healthcare Partners, PA Ms. Reeve Chace Linda Tallen and David Paul Kane SynDevRx Ms. Debra A. Charest Educational and Research Foundation UCB Biopharma David E. Clark, MD Maine Brain Aneurysm Mr. Robert M. Coleman Awareness Committee Collaborative Partners Mrs. Deborah A. Corbeau Maine Cancer Foundation Mrs. Lisa A. Cox Maine Technology Institute Dartmouth College Geisel School of Medicine Mr. Danny E. Cummings Nancy Lurie Marks Family Foundation Dartmouth Primary Care Cooperative Ms. Aleha M. Cushman Patient-Centered Outcomes Research Network (Dartmouth COOP) Ms. Jo-Ann C. Cyr Research Institute Northeastern University and Ms. Stephanie Daggett Sidney R. Baer, Jr. Foundation Ms. Elizabeth L. Davis Simons Foundation the Roux Institute Joseph R. D. deKay, DO Society to Improve Diagnosis in Medicine SYNERGY CTSI Community- Mr. Roberto P. Delima The American Cancer Society Engaged Research Core Vevergen D. Delima Tufts Clinical and Translational Research The Jackson Laboratory Ms. Victoria DeMambro Tufts Graduate School of Biomedical Sciences Ms. Sheila Descoteaux Institute Pilot Project Program Tufts University School of Medicine Clinical Ms. Anne M. Dew Natalie V. Zucker Research Center and Translational Science Institute Ms. Melody M. Doughty University of New England Ms. Catherine E. Dumont for Women Scholars Award University of Maine System Dr. and Mrs. Howard M. Ecker ZOLL Foundation University of Vermont (list continues next page) 2021 YEAR IN REVIEW 8

NOTEWORTHY ACKNOWLEDGEMENTS continued Individuals Ms. Virginia Heye-Dane Mr. Paul J. Levesque Ms. Sydney J. Hobart Mrs. Cathy L. Lowe Ms. Ashley D. Eldridge Dr. Gui Holck Dr. and Mrs. David C. Mackenzie Ms. Cathleen M. Emery Mr. Thomas W. Holden and Mr. and Mrs. Paul P. Maille Ivette F. Emery, Ph.D. Ms. Mary Quimby Ms. Christine L. Mariano Mrs. Noela L. Esakobibi Ms. Heather Holt Mrs. Dominica L. Martell Mr. Michael J. Faietta Mrs. Christina L. Hooper Mr. Thomas W. Martin Madge C. Fairfax Trust Horwitz Family Fund Ms. Danielle S. May Mrs. Jennifer L. Faucher Ms. Noreen S. Hutcherson Mr. Rick S. McAllister Ms. Sharon M. Ferrante Yongri Jin, Ph.D. Mr. and Mrs. James A. McBrady, Jr. Mrs. Robin M. Ferrar Ms. Cheryl L. Jones Mr. Mark S. McBride, Jr. Dr. and Mrs. David G. Fitz Mrs. Medrilina J. Jumapit Ms. Shelby J. McDonnell Ms. Sally G. Flanagan Mrs. Doreen A. Kacer Mr. Craig D. McGivney Ms. Natalie L. Fox Mr. and Mrs. Philip B. Kane Ms. Faith M. McNeil Robert E. Friesel, Ph.D. Mr. David Kleibacker Ms. Tracie Meersman Mrs. Sarah Gabrielson Mrs. Jennifer Klimko Ms. Samantha Migdail-Smith Mr. Kevin E. Gagnon Mrs. Ellen J. Knight Ms. Michelle M. Miles Pruitt Mrs. Theresa A. Gallupe Neil Korsen, MD, M.S. Mr. Joel P. Miller, PA-C Ms. Kimberly Gammon Robert A. Koza, Ph.D. Mrs. Samantha R. Misiuk Ms. Rita Garneau Mrs. Catherine Kruithoff Ms. Wanda Mitchell Ms. Krista M. Garrison Mr. Nicholas R. LaCourse Mr. Tige A. Monacelli Thomas Gridley, Ph.D. Dr. Jeanne Lambrew Ms. Meaghan L. Moody Mr. and Mrs. Raymond K. Grossman Mrs. Patricia Lambrew Ms. Brittney D. Moore Mr. Christian J. Guthrie Mr. and Mrs. Robert P. Lancaster Mrs. Susan M. Mortenson Ms. Melinda Hamilton Mrs. Jacqueline LaPointe Dr. Katherine J. Motyl Xianghua Han, M.D. Ms. Elizabeth J. Laube Mr. James W. Murray Ms. Lynn R. Hanscomb Mrs. Ashley M. Lavoie Mrs. Deane L. Mushlit Ms. Heidi N. Hansen Ms. Phuong T. Le Ms. Julianna D. Myers Mr. Jacob M. Hanstein Ms. Marita D. Leach Ms. Susan M. O’Brien Mr. Thomas Harvey Mr. Michael R. Lehoux Ms. Meredith B. Oestreicher Mrs. Mollie K. Heron Mr. Peter A. LePage Ms. Barbara M. O’Leary Mrs. Deborah D. Hersey Amanda Lessard, Ph.D. Ms. Rebecca M. Oliver-Palanca 9 MAINE MEDICAL CENTER RESEARCH INSTITUTE

Ms. Colleen M. O’Neill Douglas B. Sawyer, M.D., Ph.D. Mrs. Laura Trimboli Harold L. Osher, MD Captain Jared M. Sawyer Ms. Elizabeth M. Valcourt Mrs. Melissa M. Page Ms. Cynthia Scarpaci Mr. and Mrs. William S. Van Benthuysen Ms. Jennifer L. Parisien Ms. Martha Scott Ms. Heather Vickerson Mrs. Melissa Pennell Ms. Leah M. Seften Mrs. Aleksandra Vujanic Ms. Margaret D. Philbrick Ms. Eileen T. Shanahan Officer Joseph J. Wachter Mrs. Jill M. Prescott Mrs. Angela M. Smith Ms. Nicole L. Wagner Mrs. Kathleen E. Ramsdell Daniel I. Spratt, MD Jennifer Wallace, M.A. Mrs. Jacqueline A. Rancourt Mrs. Melanie Stanley Ms. Yvonne E. Wallace Ms. Abigail C. Randall Mrs. Judith Stein Ms. Kathleen Walsh Ms. Leigh G. Raposo Tania D. Strout, Ph.D. Mr. Leo B. Waterston Ms. Harmony Renna Ms. Gwendolyn M. Swan Mrs. Tina M. Whipkey Mr. Ricardo Reyes Mr. Alexander J. Szafran Ms. Molly M. White Mrs. JanAlicia Ricker Mrs. Mary Tardie Ms. Catherine Whorf Ms. Maria Rivet Ms. Megan A. Thibault Ms. Johneisha J. Williams Mrs. Bethany J. Rocheleau Ms. Kristin M. Thomes Ms. Ashley Willoughby Mrs. Amanda Rodriquez Mrs. Wanda L. Thompson Ms. Cheryl L. Winslow Mr. Spencer J. Rust Mr. Cameron J. Tracy Mr. Michael Yu Ms. Susan L. Santangelo Ms. Diane B. Tracy Ms. Lisa K. Zeien Mrs. Gabriella Sargent Ms. Debra J. Trautman Summer Student Research Program Benefactors Thank you to the following benefactors for their generous support of MMCRI’s 2021 Summer Student Research Program. This program offers opportunities for undergraduates and medical students to participate in robust academic year internships as well as intensive 10 week summer experiences. Harold L. Berry Fund for Heart Konkel Family Endowed Fund & Cancer Research for Research Scholarship Diane Cavanagh Scholarship Medical Mutual Insurance Company of Maine for Oncology Research Randy Darby Memorial Fund Chester H. & Margaret W. Pease Fund for Paul Gray Memorial Fund Cancer and Heart Disease Research Thomas W. Holden & John and Holly Benoit Twombly Scholarship Endowed Fund for Research Education Dana and Hilda Ray Willard Endowed Fund for Research Education And thank you to the dozens of other supporters who give and wish to remain anonymous. 2021 YEAR IN REVIEW 10

COVID-19 RESEARCH POPULATION & HEALTH SERVICES RESEARCH BASIC & TRANSLATIONAL RESEARCH CLINICAL RESEARCH & CLINICAL TRIALS

COVID-19 RESEARCH Research Highlights We are grateful for MaineHealth care team members’ tireless and compassionate care for COVID-19 patients. Our investigators and physician scientists have been working to address the COVID-19 pandemic through a number of important research efforts. Of note, over this past year we have continued to participate in clinical trials focused on how to improve the care of hospitalized patients, and we have investigated how to help overcome COVID-19 vaccine hesitancy in rural Maine and how best to provide COVID-19 surveillance testing in high risk populations. We are also studying the long-term effects of COVID-19. As the COVID-19 pandemic continues to evolve, some gaps in our knowledge will narrow or close, and new ones will be identified. MaineHealth is committed to investing in research that will improve patient outcomes with COVID-19, as well as working together and keeping our community safe. Read about some of the COVID-19 research taking place throughout MaineHealth in the next several pages. COVID-19 TESTING IN HIGHER RISK COMMUNITIES In September, The National Institutes of Health (NIH) As part of the study, MMCRI will work with organizations awarded MaineHealth a large grant to study ways to make including Preble Street and Greater Portland Health regular COVID-19 testing more accessible to Maine’s to increase access to walk-up COVID-19 testing sites in immigrant, low-income and homeless populations. The grant, Portland. MMCRI also will collaborate with ProsperityME part of the NIH’s Rapid Acceleration of Diagnostics-Underserved to develop insights into the cultural, Populations (RADx-UP) program, behavioral, economic and other is a supplement to MaineHealth’s factors impacting people’s decision- Northern New England Clinical making about testing. Staff with and Translational Research Network the City of Portland’s Public Health grant to expand clinical research in Division will participate in advisory the region and address the needs of underserved populations. committees to aid the research. The study is being led by Kathleen Fairfield, MD, MPH, The research team will follow 150 people from Greater DrPH, of Maine Medical Center and Maine Medical Center Portland’s immigrant, low-income and homeless population Research Institute (MMCRI) and MaineHealth’s Vice for one year to see if their attitudes toward getting regular President of Research, Elizabeth Jacobs, MD, MAPP. They COVID-19 testing has changed and whether the interventions will be collaborating with community partners to reduce result in increased testing. barriers to testing and use a variety of messaging strategies to encourage at-risk populations to get tested regularly. “This grant doesn’t just fund important COVID-19 research at MaineHealth,” Dr. Jacobs said. “It provides additional “We know that we need to use a variety of strategies to contain financial resources to our partner organizations so they can this pandemic, including masking and equitable access to continue their essential work of improving health equity and testing and vaccination,” said Dr. Fairfield. “This study is about community engagement with the health care system.” how we make COVID-19 testing accessible and acceptable to populations who are at higher risk of contracting COVID, and The study is underway and testing sites are expected to open build trust with the medical community.” by the end of 2021. For more information: radx-up.org MAINE MEDICAL CENTER RESEARCH INSTITUTE: 2021 YEAR IN REVIEW 12

COVID-19 RESEARCH RESEARCHING LONG-TERM EFFECTS OF COVID-19 In November MaineHealth received approximately $1.5 million The team at MMCRI will be enrolling approximately 90 adult from the National Institutes of Health (NIH) for up to four years patients from across the MaineHealth service area in the study. to participate in a nationwide study of the long-term effects One cohort will be patients with a recent COVID-19 infection, of COVID-19. Researchers from the Maine Medical Center a second group will be patients with a past history of COVID Research Institute (MMCRI) will be among those at more than who may or may not continue to have symptoms, and the third Cliff Rosen, MD and Ivette Emery, PhD 30 institutions across the country participating in the NIH cohort will be composed of healthy volunteers. Researchers will Researching COVID to Enhance Recovery (RECOVER) examine data including clinical information, laboratory tests and Initiative. The grant comes to MaineHealth as a subaward other analyses. They will try to narrow in on risk and resiliency from West Virginia University (WVU), a partner site. WVU factors for long COVID, as well as the impact the Alpha and and MaineHealth are leading an 11-site consortium across the Delta variants of the virus had on prevalence of the disease. country that will enroll patients in the study, with a focus on rural and underserved communities. “The RECOVER initiative aims to study long COVID across a diverse cross-section of the population, and it’s important NIH launched the RECOVER Initiative to learn why some that Maine’s rural, older population is represented,” said people have prolonged symptoms (referred to as “long Cliff Rosen, MD, Director of the Center for Clinical and COVID”) or develop new or returning symptoms after the Translational Research at MMCRI and Principal Investigator acute phase of infection from SARS-CoV-2, the virus that for the MaineHealth RECOVER site. “Together with causes COVID-19. The most common symptoms include pain, researchers across the country, we hope to make a significant headaches, fatigue, “brain fog,” shortness of breath, anxiety, contribution to the science of how those suffering from long depression, fever, chronic cough and sleep problems. COVID can get their lives back.” “While it’s clear that many patients continue to suffer COVID While the work at MMCRI will focus on the adult population, symptoms for months after recovery, we still don’t know why,” other RECOVER sites will enroll pediatric and pregnant said Ivette Emery, PhD, translational scientist at MMCRI and participants too. The RECOVER Initiative is funded for co-Investigator for the MaineHealth RECOVER site. “This four years, though the size of the study could allow for some study hopes to answer that question and find some ways to preliminary findings within just a few months. bring relief to those experiencing long COVID.” 13 MAINE MEDICAL CENTER RESEARCH INSTITUTE

NNE-CTR PILOT PROJECT GRANT: UNDERSTANDING COVID-19 VACCINE HESITANCY IN RURAL MAINE Vaccine hesitancy has been in the news frequently over this past year. The World Health Organization defines vaccine hesitancy as a “delay in acceptance or refusal of vaccination despite availability of vaccination services.” There has been significant hesitancy to receive a COVID-19 vaccine in some populations, including rural communities, despite the fact Kathleen Fairfield, MD, DrPH, and Elizabeth Jacob’s MD, MAPP that the vaccines have been clinically proven to be safe and effective at preventing severe illness, hospitalization, and death. Kathleen Fairfield, MD, DrPH, and Elizabeth Jacobs MD, MAPP applied for and received a pilot grant award from the Northern New England Clinical & Translational Research Network (NNE-CTR see page 5) to study vaccine hesitancy in rural Maine. This pilot funded interviews and surveys of Maine residents in four rural counties about the COVID-19 vaccination, and the findings were used to create and pilot community messaging to encourage Mainers to speak with a trusted physician about vaccination. They found that hesitancy arises from misperceptions about the risk of COVID-19, distrust of government organizations and agencies, and misinformation about the safety of the COVID-19 vaccines and conspiracy theories surrounding them. They also found that what motivated people who were initially hesitant to get the vaccine was the encouragement of their friends and families, a desire to keep a friend or family member safe, and the recommendation of a trusted health care provider.. Vaccinating a substantial proportion of Americans with an effective COVID-19 vaccine is critical to bringing the COVID-19 pandemic to an end. The research team is hopeful these results can inform our vaccine efforts in Maine and beyond. WHAT IS A PILOT PROJECT? A CATALYST FOR RESEARCH. Sometimes a research study requires Network, two Centers of Biomedical initial experiments prior to launching Research Excellence (COBREs), and the full study. A pilot project is a smaller institutional cardiovascular center study that can usually be performed in programs all provide pilot project a limited time frame (usually within 1 funding to researchers to get a new idea year), and may be designed to establish off of the ground. Pilot project funding feasibility, experimental models, may lead to revisions or improvements protocols, samples, or procedures for a in the plan of a larger research study, larger study. Our Northern New England data for a larger grant application, and Clinical & Translational Research abstracts/publications. 2021 YEAR IN REVIEW 14

COVID-19 RESEARCH AUXORA SHOWS PROMISE FOR THE TREATMENT OF SEVERE COVID-19 PNEUMONIA Kathryn Brouillette, MD, pediatrics and internal medicine physician, is the principal investigator of a Maine Medical Center study of the drug Auxora for treatment of severe COVID-19 pneumonia. CalciMedica Inc., a clinical-stage biopharmaceutical company, launched its CARDEA trial (A Randomized Double Blind, Placebo-Controlled Study of Auxora for the Treatment of Severe COVID-19 Pneumonia) in September 2020, with 40 institutions and a recruitment goal of 400 subjects. Due to waning COVID-19 cases in the spring of 2021, and changes in standard of care, recruitment was halted at 284 subjects. Maine Medical Center recruited 12 of these. Auxora is a drug that blocks calcium signaling in cells of lung and blood vessels, reducing the inflammation that causes lung and blood vessel injury in severe COVID-19. Previously, Auxora showed promise in preventing lung tissue damage and ARDS (acute respiratory distress syndrome) in preclinical genetic models of severe pancreatitis. Phase 2b trials are designed to rigorously test a drug’s ability to treat or prevent a disease. During the winter surge of the pandemic, a CARDEA Phase 2b trial was conducted with patients with severe COVID-19 pneumonia, requiring low- and high-flow nasal oxygen supplementation to assist breathing. Preliminary results of this trial showed improvement in time to recover, mortality, and rates of serious adverse events. The study completed at Maine Medical Center in June 2021. A second trial will launch this winter to study Auxora’s efficacy and safety for those with higher oxygen requirements. Maine Medical Center will likely participate in this second trial. IT-19 Cytology analysis of a COVID-19 patient who died shows neutrophils with IT-19 stands for Immunological Targets for COVID-19 treatment. This study extruded DNA entangled among red began in 2020 with the purpose of helping scientists better understand the blood cells. Provided by Drs. Victoria immune system response to COVID-19 infection. Researchers evaluated the Herrera and Nelson Ruiz-Opazo, effects of COVID-19 on the immune system to identify new therapeutic targets. collaborators at Boston University It involved blood draws on certain days, and for patients who needed a ventilator, a sputum test to detect and identify bacteria or fungi that infect respiratory epithelium that cause inflammation in the lungs and breathing passages. This research is an example of basic and clinical researchers collaborating; the Principal Investigators were Sergey Ryzhov, MD, PhD, Faculty Scientist at MMCRI, and David Seder, MD, Chief of Critical Care Services, at MMC. The study was completed in June 2021, with results demonstrating the association between immune cells that promote inflammation, so-called DEspR expressing neutrophils, and severe and critical COVID-19 illness. Looking ahead, Drs. Ryzhov and Seder are going to develop a therapeutic approach that will block this aggressive DEspR neutrophil and reduce secondary tissue damage in critically ill patients. 15 MAINE MEDICAL CENTER RESEARCH INSTITUTE

ACTIV4-C TRIAL FOCUSES ON PREVENTIVE TREATMENT AFTER HOSPITALIZATION FOR COVID-19 PATIENTS Dan Meyer, MD, is the Division Director for Hospital factors for thrombosis may extend beyond the hospitalization Medicine at Maine Medical Center and the Principal itself. Patients with COVID-19 present a particularly high Investigator on the ACTIV4-c trial, assisted by Terilee Gerry, risk group. These patients are more prone to developing clots. MSRN, Research Coordinator. This trial seeks to answer The ACTIV4-c trial seeks to answer whether continuing the question of whether patients with COVID-19 who are low dose apixaban, an oral blood thinner, continued after hospitalized for their illness benefit from ongoing prophylaxis hospitalization, is beneficial for patients. A double-blind (preventative healthcare) against venous thromboembolism, multi-center randomized placebo controlled trial, ACTIV4-c otherwise known as blood clots, in the post-hospital period. seeks to enroll 5000 patients to help answer this important Previous research shows that hospitalized patients, especially question. The trial is also being conducted at another those with high risk conditions such as cancer or stroke, MaineHealth site, Pen Bay Medical Center, where Robert benefit from receiving prophylactic blood thinners while Stein, MD, is the Principal Investigator. The results of the hospitalized. These medications reduce risk of complications trial will inform future directions of research and a finding of and are now part of the standard of care for most patients. benefit from prophylactic blood thinners would likely result For many years clinicians have not had rigorous data to guide in trials expanding to other illnesses beyond COVID-19. treatment for patients after discharge even though the risk L to R: Matt Clark, MD (Sub-Investigator), Terilee Gerry, MSRN (Research Coordinator) and Daniel Meyer, MD (Principal Investigator) Not Pictured: Sarah Bray, MD (Sub-Investigator), Kathryn Brouillette, MD (Sub-Investigator), Jenna Ptaschinski, MD (Sub-Investigator) and Debra Burris, RN, CCRC (Clinical Research Coordinator) 2021 YEAR IN REVIEW 16

COVID-19 RESEARCH Lindsey Gower, Technology Manager, with instrumentation used for analyzing the test reaction. COLLABORATIONS DRIVE PROMISING TESTING SOLUTIONS FOR COVID-19 When COVID-19 testing supplies were in extreme short supply worldwide, NorDx Laboratories, a member of MaineHealth, began searching for alternative testing methods. NorDx identified Sherlock Biosciences, an Engineering Biology company that provides diagnostic testing, as a potential partner to explore an alternative. Initially the testing method lacked automation capabilities but through the collaboration the team identified procedures to automate the liquid handling portion of the method. In June, Sherlock Biosciences announced initial results from an automation study of its CRISPR-based test for SARS-CoV-2 (COVID-19) in partnership with NorDx. The study was the first-ever successful automation of a CRISPR test that enabled laboratories to test clinical samples from thousands of patients a day on a single system, streamlining workflows and improving patient outcomes. MMCRI’s Research Laboratory Services (RLS) division provided the instrumentation necessary for detecting and analyzing the test reaction for the novel CRISPR-based test for SARS-CoV-2. According to Anne Breggia, PhD, Director of the MMC BioBank and RLS division, “We are proud to have assisted in the initial testing for this assay and look forward to working with NorDx and the Sherlock team in the next phase of test development and validation.” Beyond testing for COVID-19, the CRISPR method holds great promise to complement existing technologies including point of care needs. According to Robert Carlson, MD, Medical Director NorDx, “This serves as an example of the benefit of collaborations between NorDx, MMCRI and industry to drive promising innovation from the research bench to patient care applications.” 17 MAINE MEDICAL CENTER RESEARCH INSTITUTE

INNOVATIVE COVID-19 DATA PLATFORM JUMPSTARTS COVID RESEARCH ON A NATIONAL SCALE MaineHealth has been part of a landmark development in in a manner that protects patient privacy. In addition to the clinical research. The National COVID Cohort Collaborative vast amounts of data available for coronavirus research, N3C (N3C) was created in September 2020 in response to the provides opportunities for team science and collaboration COVID-19 pandemic. It is a data analytics platform with experts in statistics, machine learning, informatics, for research on the largest repository of COVID-19 clinical data in the world. N3C pharmaceuticals, and many clinical domains. includes data from more than 3 million COVID-19 patients contributed by over 50 This year, MaineHealth is helping to take health care organizations nationwide, including MaineHealth. N3C to the next level. We are participating Susan L. Santangelo, Director of the Center for Psychiatric in an innovative process of linking N3C Research at Maine Medical Center Research Institute, is the data with additional datasets, including data on COVID-19 Principal Investigator for N3C at MaineHealth. genetic variants. The process, which preserves patient privacy, significantly expands the research potential into exciting N3C allows investigators to rapidly conduct groundbreaking new avenues. MaineHealth is partnering with NorDx and COVID-19 research with real world data from electronic the Jackson Laboratory in this next level of COVID-19 health records. Over 9 billion data rows are available in N3C. research analytics. The data include information about each patient, including their diagnosis, treatments, lab results, and healthcare provider, N3C is funded by the National Institutes of Health. For more information: covid.cd2h.org COMMUNICATING ABOUT COVID-19: STRATEGIES FOR PROMOTING RISK-REDUCING ON FACEBOOK One manifestation of the COVID-19 pandemic has been about COVID-19 risk-reducing behaviors were paired with anti-social, stigmatizing behaviors. Social psychological the message frames and ran on Facebook. The campaign research has demonstrated that uncertainty and fear reached over 119,000 Maine residents and generated 8,639 substantially contribute to the stigmatization of infectious website clicks and 433 pledges. Importantly, messages about diseases like COVID-19. COVID-19 stigmatization is COVID-19 that used the destigmatizing frame generated associated with delayed treatment and poor testing more social media engagement than any other strategy. uptake; thus, controlling the pandemic requires health This is promising preliminary evidence suggesting that communication strategies that promote risk-reduction destigmatizing communication strategies can generate without inadvertently perpetuating stigma. In collaboration public interest in COVID-19 risk-reduction, with the with the Maine Centers for Disease Control, Liz Scharnetzki, theoretical benefit of not eliciting fear or blame. More PhD, Leo Waterston, MA, and Paul Han, MD, MA, MPH, research is needed to replicate these findings in other conducted a social media-based factorial experiment to populations. The research team is reviewing plans for follow test the efficacy of two novel public health message frames up studies, and thus far has conducted one related study — destigmatizing and normalizing uncertainty — relative using the destigmatizing frame to understand if this strategy to existing messaging strategies in generating public can be applied to multiple disease tracks. interest in COVID-19 risk-reducing behaviors. Messages 2021 YEAR IN REVIEW 18

POPULATION & HEALTH SERVICES RESEARCH REDUCING LUNG CANCER IN MAINE In October Neil Korsen, MD, MSc, Faculty Scientist in the Center for Outcomes Research and Evaluation, was awarded a grant from the Maine Cancer Foundation for the “Maine Lung Cancer Coalition — Second Generation”, which will continue its work to reduce the burden of lung cancer in Maine. The Maine Lung Cancer Coalition (MLCC) is a statewide, multi-sector partnership that conducts research and data analysis, clinical practice and quality improvement, policy and advocacy, and implementation and messaging to address the lung cancer problem in the state. The grant will allow the MLCC to continue its work by transitioning to a Collective Impact model with a small backbone staff and multidisciplinary work groups to address short and long-term goals. The Collective Impact Neil Korsen, MD, MSc model is a framework that calls upon different stakeholders to collaborate in a structured way towards shared impact outcomes. The new grant will allow the MLCC to continue to work on risk reduction through attention to tobacco and radon and on spreading information about the new lung cancer screening guidelines, which have increased the number of people eligible for screening. The research team will have a particular focus on addressing the stigma that is often associated with tobacco use and lung cancer. RESEARCH SHEDS LIGHT ON ENVIRONMENT CHEMICAL RISKS IN ADOLESCENCE Perfluroalkyl and polyfluoroalkyl substances, or PFAS as they are commonly called, have been around since the 1940s, and in recent years have gained attention in the news both nationally and in Maine due to their harmful effects. PFAS are synthetic chemicals added to clothing, furniture and carpets to make the items non-stick and stain repellant. PFAS, often referred to as “forever chemicals,” don’t naturally break down, so they stay in our bodies for years and in the environment for decades. Studies in animals suggest that these classes of chemicals may disrupt common biological pathways and increase the risk of both high body fat and low bone mineral density. Abby Fleisch, MD, MPH Abby Fleisch, MD, MPH, a pediatric endocrinologist at Maine Medical Center and Faculty Scientist at Maine Medical Center Research Institute, is the Principal Investigator on an NIH National Institute of Environmental Health Sciences grant to study this chemical and evaluate if it may be contributing to obesity in teenagers, potentially making those teens more susceptible to osteoporosis later in life. The study uses data from about 500 teenagers who have been enrolled since birth in Project Viva, a longitudinal research study of mothers and children in Eastern Massachusetts. The study is under way and has been testing for PFAS in samples of the teens’ blood and for phthalates (another environmental chemical) in their urine, as well as measuring body fat and bone mineral density using a special kind of X-ray machine. 19 MAINE MEDICAL CENTER RESEARCH INSTITUTE

To help guide effective preventive interventions, it is critical to understand how chemicals in the environment may impact our health, I am excited to be involved in this study and to be a part of the legislative process to create thoughtful policies surrounding PFAS production and use in Maine. — Abby Fleisch, MD, MPH Research results from this year demonstrate that children with higher concentrations of select PFAS had lower bone mineral density and net adverse changes in body composition, including less accrual of lean mass and greater accrual of visceral fat mass (fat stored around the organs in the abdomen). Girls with higher concentrations of select PFAS had delayed puberty. This work is especially important in Maine, where the concern over PFAS is hitting close to home. The Somerset County town of Fairfield remains at the center of the largest state investigation of the long-term impact of PFAS on health and properties. In addition, Governor Mills established a task force in 2019 for managing PFAS in Maine. Also, several state bills to monitor and eliminate PFAS were put into law this year, including one for which Dr. Fleisch testified on behalf of the Maine chapter of the American Academy of Pediatrics MAINE CANCER GENOMICS INITIATIVE CONTINUES TO BRING NOVEL TREATMENTS TO CANCER PATIENTS Investigators at the Center for Outcomes Research and Evaluation (CORE) are partnering with The Jackson Laboratory (JAX) to launch the second phase of the Maine Cancer Genomics Initiative (MCGI), a program of The Jackson Laboratory. Eric Anderson, PhD, Staff Scientist, and Lee Lucas, RN, PhD, Faculty Scientist, will lead CORE’s efforts while JAX’s team will be under the direction of Principal Investigator Jens Reuter, MD. Funded by the Harold Alfond foundation, the MCGI is a statewide partnership aimed at giving Maine cancer patients and their doctors the opportunity to access, understand and effectively use evolving genomic tumor testing in cancer care. During the first phase of funding (2016-2021), the initiative successfully established the first Genomic Medicine Network in Maine, developed a physician education program about clinical genomic cancer tests, and provided free genomic tumor testing to over 1600 oncology patients. With an additional five years of funding, future plans include maximizing the impact of precision oncology on cancer patients and oncologists in Maine through enhanced actionability, interpretability and accessibility; while improving the delivery of precision oncology in rural settings through continued community building and iterative learning. The MCGI has already become a widely-recognized statewide collaboration, and with renewed support from the Alfond Foundation, hopes to serve as a model for community precision oncology in rural settings. 2021 YEAR IN REVIEW 20

BASIC & TRANSLATIONAL RESEARCH BUILDING RESEARCH EXCELLENCE IN UNDERSTANDING CAUSES OF METABOLIC DISEASE In September 2017, MMCRI was awarded a five-year, $11 million Center of Biomedical Research Excellence (COBRE) grant by the National Institutes of Health to establish a multidisciplinary research center to model the basis of human metabolic health and disease. The goal of this COBRE is to address obesity, osteoporosis and diabetes — all metabolic diseases common in Maine — by understanding pathways that lead to these disorders. This Cliff Rosen, MD and COBRE in Metabolic Networks has been very successful in its first four years of funding. Lucy Liaw, PhD The COBRE is led by Lucy Liaw PhD, MMCRI Faculty Scientist and Director of Research Training & Education with support from Cliff Rosen MD, Director of the Center for Clinical & Translational Research, and Irwin Brodsky, MD, Maine Medical Partners Endocrinologist and Clinical Advisor. Under Dr. Liaw’s leadership there has been development of a critical mass of investigators with biomedical research interests in metabolic health and disease, supported by state-of-the art technical shared resources. In addition, a robust mentoring network has been established for junior investigator project leaders, as well as a strong research infrastructure to allow this group to thrive. 2021 Brings Two National Institutes of Health R01 Awards for COBRE Junior Investigators Both Aaron Brown PhD, and Katherine Motyl PhD, received the National Institutes of Health (NIH) R01 awards to advance their careers as independent investigators. The NIH R01 is the “gold standard” of research grants awarded by the National Institutes of Health. It is generally a four to five year grant in the range of $250,000-$500,000 direct costs per year and is an investigator-initiated research project addressing a biomedical question that can be basic, translational or clinical research. The five years give the researcher time needed to achieve publishable results. R01s are highly competitive; roughly 19% of R01s are funded by NIH each year. MMCRI’s track record in obtaining R01s reflects a rich scientific and academic environment that provides the resources, research infrastructure, and intellectual support for investigator success. These R01s represent first time awards for Drs. Brown and Motyl; Dr. Michaeala Reagan also received her first R01 a year ago. All three began as junior investigators on the COBRE in Metabolic Networks grant. The details of this year’s awards are outlined below. Katherine Motyl PhD: $1.8M to study how the nervous system affects bone In May 2021, Dr. Motyl was awarded a five-year grant from the National Institutes of Health’s National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Motyl and her team will examine how the sympathetic nervous system (SNS) communicates with osteoclasts (cells that dissolve bone) through beta adrenergic receptors and how this pathway contributes to age- and SNS- Katie Motyl, PhD related bone loss. This research will also provide a more complete understanding of how commonly prescribed beta-blockers may help prevent osteoporosis. Co-Investigators are Karen Houseknecht PhD, Professor of Pharmacology and Associate Provost for Research and Scholarship, University of New England, and Christine Lary, PhD, Senior Biostatistician and Faculty Scientist I, Center for Outcomes Research & Evaluation at MMCRI. 21 MAINE MEDICAL CENTER RESEARCH INSTITUTE

Aaron Brown PhD: $2.1M to study a type of fat & its energy burning capacity The Brown Laboratory studies brown fat, which can burn excess calories due to the Aaron Brown, PhD presence of specialized mitochondria, the powerhouse of the cell. Brown fat is activated in response to cold, and it converts the calories we eat Immunohistochemistry image showing large lobules of multilocular, UCP1 positive beige fat cells into heat to keep our bodies warm. More active brown fat is also (brown colored stain, bottom half of tissue section) forming in subcutaneous adipose tissue after mice associated with a reduced risk of metabolic diseases, making it a are exposed to colder temperatures. These beige fat cells contain specialized mitochondria that burn candidate tissue for therapies. Dr. Brown and his team discovered energy and can be distinguished from the larger, unilocular white adipocytes that store energy a group of genes that may enhance the energy burning capacity (white colored with blue hematoxylin counterstain, top half of the tissue section). Formation of beige of brown fat. In September 2021, Dr. Brown received this five fat cells during cold exposure is associated with resistance to obesity and type 2 diabetes. year award from NIH’s National Institute of Diabetes, Digestive and Kidney Diseases. This funding will help him and his team examine brown fat further and aid in better understanding of how the mitochondria that are found in brown fat burn energy. NIH Equipment Grant Expands Metabolic Research The COBRE in Metabolic Networks also supports the expansion of state-of-the-art technology, including advanced protein and lipid analysis and bone measurements, and the assessment of histopathology, physiology and body metabolism. In September 2021, Dr. Liaw received an NIH award on behalf of the COBRE in Metabolic Networks for instrumentation that will support and expand metabolic phenotyping equipment in the Physiology Core Facility at MMCRI. This new award will be used to purchase metabolic cages to closely monitor food and water consumption, activity, sleep, energy expenditure, and other behaviors in pre-clinical genetic models of disease. In addition, it will allow measurement of metabolism at different temperatures. Temperature studies are important since cold activates calorie-burning adipocytes (brown or beige), which is an anti-obesity strategy. “This metabolic and behavioral profiling is critical in our use of model organisms to study obesity, diabetes, and overall body metabolism”, Dr. Liaw said. “These analyses will help us understand and apply our findings to improving metabolic health of patients.” Looking ahead, the COBRE in Metabolic Networks has applied for renewal funding to continue research projects that encompass clinical and community-based as well as genetic studies, recruit further expertise to enhance and diversify MMCRI’s research community, and focus on strong multi-disciplinary mentoring to advance translation studies. COBRE in Metabolic Networks: mmcri.org/metabolic_cobre 2021 YEAR IN REVIEW 22

BASIC & TRANSLATIONAL RESEARCH (L) Joe Nadeau, PhD, MMCRI Faculty Scientist and (R) JOE NADEAU, PHD, RECEIVES RARE Andrew Pospisilik, PhD, Van Andel Institute TRANSFORMATIVE RESEARCH AWARD Joe Nadeau, PhD, Faculty Scientist at Maine Medical Center Research Institute recently received a Director’s Transformative Research Award from the National Institutes of Health (NIH). Dr. Nadeau is a Principal Investigator on this collaborative $9.6M grant with Dr. Andrew Pospisilik of the Van Andel Institute, Grand Rapids, MI. Working with Dr. Nadeau is co-investigator Dr. Christine Lary, Senior Biostatistician and Faculty Scientist at MMCRI. Dr. Nadeau and team will explore the factors that are neither nature (genes) nor nurture (environment), but that account for who we are as individuals and for our unique risks for disease. Asking questions such as: “If you were born multiple times under the exact same circumstances, would you turn out to be the same person each time?” “And if not, what implications could the differences have for your health?” The answers to these questions could change our understanding of how “probabilistic” variation influences health before birth and throughout life — and provide insights into new strategies for combating cancer, obesity and a host of other health concerns and diseases. This work will focus on mouse models of obesity and related metabolic conditions and will include tests to determine whether findings are relevant to human health and disease. This award is part of NIH’s High-Risk, High-Reward Research program. The award supports individuals or teams proposing transformative projects that are inherently risky and untested but have the potential to create or overturn fundamental paradigms . RESEARCH ON LYME DISEASE & IMPACT OF CLIMATE CHANGE ON TICKS In 2021, MMCRI’s Vector-Borne Disease (VBD) lab continued its partnership with Tufts University on its Lyme Disease Initiative. Robert Smith, MD, MPH, an infectious disease physician, is Director of the VBD lab and the co-director of the Tufts Lyme Disease Initiative with physician Linden Hu, MD, Professor of Immunology and Vice Dean for Research at Tufts University School of Medicine. The initiative promotes interdisciplinary research in all aspects of Lyme disease, with the goal of eradicating it as a rising human health problem by 2030. Several of the approaches include investigating ways to eliminate Lyme disease at its source by preventing ticks from spreading the Lyme bacteria in the wild. Looking ahead, participation in a multi-center human Lyme disease vaccine trial is slated to begin next year. With Lyme disease a growing public health threat, scientists hope this time a Lyme disease vaccine, if successful in the upcoming trial, will provide a new option for individual protection. Staff Scientist Susan Elias, MS, PhD, has continued to study the impact of climate change on blacklegged (deer) ticks in Maine. Climate change is bringing shorter winters and warmer summer and fall nights to Maine, along with higher humidity. These are all conditions that favor survival of blacklegged (deer) ticks and have allowed them to expand north and to higher elevations. To combat range expansion of ticks, white-tailed deer should not be allowed to overpopulate towns and forests, and non-native Japanese barberry should be kept out of forests, public spaces, and yards, as previous VBD lab research has shown. 23 MAINE MEDICAL CENTER RESEARCH INSTITUTE

Also in 2021, the lab monitored mosquito-borne viruses (arboviruses), particularly West Nile virus, Eastern equine encephalitis virus, and Jamestown Canyon virus. As in the past, lab staff worked with Maine-based partners to collect vector mosquitoes for testing at the Environmental Health and Testing Laboratory in Augusta. Notably, Research Associate Elizabeth (Libby) Schneider detected Jamestown Canyon virus in several species of Maine mosquitoes, including members of the genus Aedes (“odious” in ancient Greek), and was the first to find the virus in Uranotaenia sapphirina, a small mosquito with iridescent sapphire-blue scales. Staff Scientist Rebecca Robich, PhD, served as Libby’s mentor. ELEANOR LACOMBE, RESEARCHER — 1932-2021 Eleanor Lacombe, one of the founding members of Maine Medical Center Research Institute’s Vector-Borne Disease laboratory, passed away peacefully in September. Eleanor, Peter Rand, MD, and Robert Smith, MD, MPH, were the three-member nucleus that began three decades (and counting) of research on tick-borne diseases. This research took Eleanor throughout Maine from deer tagging stations to remote coastal islands. She co-authored over 60 research articles and presented her findings at academic conferences throughout the country and Europe. With humility, humor, and a rigorous attention to detail, Eleanor acted as an insightful mentor to young professionals who came through the lab. Her creative questions frequently led the lab to new and productive areas. Her research work with Dr. Rand at MMC spanned nearly 50 years, and included studies in cardiovascular physiology and environmental health, as well as vector-borne diseases. Her spirit and enthusiasm will be missed. 2021 YEAR IN REVIEW 24

CLINICAL RESEARCH & CLINICAL TRIALS Doug Sawyer, MD, PhD RESEARCH PLAYS A ROLE IN REDUCING RURAL Principal Investigator HEALTHCARE DISPARITIES IN EMERGENCY CARE Since 1991, Maine Medical Center Research Institute (MMCRI) has been at the center of MaineHealth’s mission to improve patient health and outcomes by advancing the science of medicine through biomedical research. Maine is a rural state, with disparities in healthcare based on regional variations in resources and on-site expertise. Rural patients have longer delays in care due to delayed emergency medical service responses and longer travel times for expert-level care. Disparities in rural health outcomes in conditions such as cardiac arrest are further increased by limited access to clinical research studies that evaluate and implement new protocols and technologies. In January 2021, MMCRI was awarded a five-year, $12.8 million Centers of Biomedical Research Excellence (COBRE) grant by the National Institute of General Medical Sciences of the National Institutes of Health. The funding is being used to help address these health challenges and support clinical research aimed at reducing rural health disparities in acute care settings. “This grant will not only help establish the infrastructure necessary to better serve rural communities, it will support MaineHealth engagement with community Tom Gridley, PhD members to understand their needs, and how best to focus future research,” said Co-Investigator Doug Sawyer, MD, PhD, Chief Academic Officer of Maine Medical Center and MaineHealth and the Principal Investigator of this grant. “When research works hand-in-glove with community needs and patient care, we impact health.” Dr. Tom Gridley, Associate Director of the Center for Clinical & Translational Research is the Co-Investigator for this grant. David Gagnon, PharmD Four Projects Improve Healthcare Access in Rural Communities Heading the PROTECT study The COBRE funding will be used to develop a statewide research and care network in Maine that addresses barriers associated with limited resources, expertise and access in rural areas and will begin with the support of four clinical studies. One clinical trial that is underway is the PROTECT study. David Gagnon, PharmD, a pharmacist at Maine Medical Center who specializes in Critical Care Pharmacy, is heading the study. The study examines whether giving antibiotics after cardiac arrest stops pneumonia and helps people survive and recover. It will also look at how antibiotics affect the normal bacteria in our bodies. “Currently, the best way to stop pneumonia after cardiac arrest is not known,” said Dr. Gagnon. “This study will help answer the question: “Do early antibiotics after cardiac arrest stop pneumonia and help people recover?” 25 MAINE MEDICAL CENTER RESEARCH INSTITUTE

When research works hand-in-glove with community This is a significant question, considering only 4 out of 10 needs and patient care, we impact health. people who have an out-of-hospital arrest make it to the hospital alive, and of the 4 people who make it to the hospital — Doug Sawyer, MD, PhD, Chief Academic Officer of alive, only 1 or 2 will survive. In addition, lung infection may MaineHealth, Principal Investigator happen to 6 out of 10 patients, and may lower their ability to survive and live normally. Cardiac arrest occurs when the heart suddenly stops pumping blood. In adults, this may be the result of a heart attack or other stress on the body. Pneumonia may make it harder to survive cardiac arrest. Pneumonia, and cardiac arrest in general, is associated with uncontrolled inflammation, and because inflammation and pneumonia may precipitate secondary brain injury, preventing them may improve outcomes. The PROTECT study is using ceftriaxone, an antibiotic with excellent anti-microbial spectrum, and has anti-inflammatory as well as potential neuroprotective effects. “I am excited to work towards establishing effective pharmacotherapy options for cardiac arrest survivors to improve their care across diverse communities,” said Dr. Gagnon. “Our team is focused on ensuring the approximately 60% of Mainers living in rural locations have the same access to cutting-edge research that the rest of the state does. Studies like PROTECT are an important step in making this a reality.” The three additional studies in this grant have a common thread of building healthy communities by increasing access to care and improving patient outcomes. Teresa May, DO, MS, is examining whether MaineHealth can improve rural patient outcomes after cardiac arrest by creating a standard best practice protocol for care. David Seder, MD, is leading a study looking into how the types of white blood cells patients have in their bloodstream after cardiac arrest may impact their recovery. Finally, Alexa Craig, MD, MS is conducting telemedicine research that supports rural hospitals in the rapid recognition of newborns who need treatment with therapeutic hypothermia to protect the brain. Dr. Craig also will study whether telemedicine is an effective way of gaining the consent of the parents of these newborns for research and clinical care. The COBRE will allow each of these investigators to receive mentoring and logistical support for their projects. Project leaders also will be connecting with community members to better understand the health care challenges they face so they may be addressed in future studies. Frank Chessa, PhD, and Richard Riker, MD, will oversee community engagement in clinical research, as well as research training for clinicians across MaineHealth. “This program builds upon our exceptional clinical experience and strong basic and translational research programs to focus on the challenge of increasing access to high-quality acute care in rural Maine.” said MMCRI Vice President for Research Elizabeth Jacobs, MD, “It is a unique opportunity for these promising clinician researchers and for our state.” For more information, visit mmcri.org/accobre 2021 YEAR IN REVIEW 26

CLINICAL RESEARCH & CLINICAL TRIALS RESEARCH ON OSTEOPOROSIS PREVENTION IN POST-MENOPAUSAL WOMEN Cliff Rosen, MD, Senior Faculty Scientist at MMCRI and Irwin Brodsky, MD, Endocrinologist and Affiliated Investigator at MMCRI, are collaborating with colleagues at four leading medical centers across the country to determine whether the beta blocker Atenolol, commonly used to lower blood pressure, can also help prevent osteoporosis in post- menopausal women. The Atenolol for the Prevention of Osteoporosis (APO) study was funded this year at MMCRI by a four-year $2.4 million grant from the National Institutes of Health’s National Institute on Aging; the study is coordinated by the Mayo Clinic and also includes Columbia University Medical Center and the University of California at San Francisco. The grant was a result of major collaborative efforts that included translational research at MMCRI, from the laboratory of Drs. Katherine Motyl and Christine Lary, and translational efforts at the Mayo Clinic, including a small pilot trial conducted by Dr. Khosla. Menopause is a known risk factor for osteoporosis, a condition that weakens the bones, putting a person at risk for bone fractures. New research suggests that certain nerves that increase heart rate and blood pressure may also cause loss of bone strength, especially after menopause. Atenolol slows the heart rate and reduces blood pressure by blocking the effect of the body‘s nerves. The study examines whether the drug may help preserve bone in doing so. Researchers will follow healthy post-menopausal women between the ages of 50-75 for two years. Participants will take a half-dose for a month to determine if they can tolerate the medication and then randomly be assigned to take a 50 milligram dose or a placebo each day for the duration of the study. Women will keep a diary of their health and symptoms and visit the study office every six months for blood and bone density tests. “Current methods of preserving bone in post-menopausal women, such as estrogen, can be effective in the short term for women in their 40s and 50s, but have the potential to cause serious side effects after age 60,” said Irwin Brodsky, MD, MPH, MMCRI’s principal investigator on this study with Clifford Rosen, MD. “Our hope is that Atenolol will improve the long-term bone health of older women with fewer side effects.” 27 MAINE MEDICAL CENTER RESEARCH INSTITUTE

CENTER OF EXCELLENCE IN AUTISM AND DEVELOPMENT DISORDERS OPENS New Building Expands Research & Creates Opportunity for Unique Study In August Maine Behavioral Healthcare (MBH), part of the MaineHealth system, opened The Glickman Lauder Center of Excellence in Autism and Developmental Disorders. This 28,000 square foot facility includes child and adult outpatient clinics, preschool and early intervention in-home services, child day treatment, all paired with clinical research and provider training. The building is designed to provide the best therapeutic environment for the population, complete with sound-dampening systems to maximize comfort, an indoor gym, special nooks and cubbies to provide quiet retreats, visual communication supports, and natural and controlled lighting that can be adjusted to meet sensory needs. In addition, state-of-the-art remote sensing technologies turn classrooms and clinic spaces into living laboratories, where individuals can participate in innovative research during the course of their regular treatment activities. While construction was underway, staff recognized an opportunity to study the effect of the environment on the learning and behaviors of preschoolers with autism. Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental disorder that affects people differently. A few characteristics of ASD include challenges with regulating sensory modalities, social communication, as well as hyper or hyposensitivity to sensory stimuli in the environment. Matthew Siegel, MD, VP of Medical Affairs for Autism and Developmental Disorders and MMCRI Faculty Scientist, teamed up with investigators from Clemson University’s Health Architecture program to do a pre/post study. This study compares variations in the environmental conditions in the former building during a two-month pre-period (where the classrooms were retro-fitted spaces designed originally for another purpose) to the new Glickman Lauder Center I am excited that our move to this incredible new center, which of Excellence (where new classrooms have been designed will catalyze and grow our current research programs, inspired a around the needs of children with autism) for a two- new study before the building even opened. This will be the first month post-period. This research attempts to answer the study to rigorously examine the relationship of changes in specific question: Will a move to a classroom purposely designed for environmental variables that people with autism are sensitive to, children with ASD reduce problem behaviors and improve including sound levels and temperature, to real-world outcomes educational growth metrics in an early childhood education in behavior and educational progress. program? At the time of press, researchers were evaluating — Matthew Seigel, MD data from the study. VP of Medical Affairs for Autism and Developmental Disorders 2021 YEAR IN REVIEW 28

CLINICAL RESEARCH & CLINICAL TRIALS INNOVATIONS TO IMPROVE OUTCOMES L to R: Kristen Woodberry, MSW, PhD, Dave Weiss PhD, EB Bernier, Abrey FOR ADOLESCENTS AND ADULTS WITH Feliccia, BA, and Katherine Elacqua (former team member)] SERIOUS MENTAL HEALTH CHALLENGES when primary care providers and embedded behavioral health Despite the challenges of COVID-19, the research team led by clinicians are trained and given the time to ask about and Kristen Woodberry, MSW, PhD, Faculty Scientist at MMCRI’s respond to early warning signs. Center for Psychiatric Research, successfully launched its first social skills group for a PCORI (Patient Centered Outcomes Additionally in October 2021, team member Dave Weiss, Research Institute) funded trial in collaboration with Beth Israel PhD, received a highly selective Marian R. Stuart grant from Deaconess Medical Center. Project SUCCESS is comparing the the American Psychological Foundation. This will support effectiveness of Social Skills Training (SST) versus Cognitive pilot research to promote smoking cessation in young adults Enhancement Training (CET) for improving social connection with psychotic disorders. Dr. Weiss’ career goal is to conduct and community functioning of patients with schizophrenia. research to reduce health disparities for individuals with The team expects to start new SST and CET groups in 2022. serious mental health challenges. Dr. Woodberry’s team also completed the first year of SEE ME Maine, a Sidney R. Baer, Jr. Foundation funded project to test the feasibility of screening for psychosis in primary care settings. Within just four months, four MaineHealth clinics screened over 300 patients ages 14-26, with behavioral health clinicians assessing positive screens to determine next steps. Screening for psychosis in primary care may be feasible EXPANDING & SHARING CLINICAL RESEARCH SKILLS Project ECHO (Extension for Community Healthcare investigators and research professionals. The online Outcomes), was developed by Sanjeev Arora, MD, at the format makes it particularly accessible to rural provider University of New Mexico Health Sciences Center. It offices. In addition, participants are able to network is a collaborative model of medical education and care with Northern New England’s growing community of management that helps clinicians provide expert-level clinician-researchers to learn about clinical research care to patients wherever they live. A Project ECHO from each other. The project launched in September on clinical trials was developed by the Professional and to date has had four sessions, with four more Development Core of the Northern New England scheduled for 2022. Clinical & Translational Research Network (NNE- CTR see page 5 for more information). This ECHO was designed for staff interested in developing clinical research skills by connecting with experienced clinical 29 MAINE MEDICAL CENTER RESEARCH INSTITUTE

GYNECOLOGICAL ONCOLOGY TEAM PLAYS A ROLE IN ADVANCING ENDOMETRIAL CANCER DRUG Leslie Bradford, MD, of Maine Medical Partners’ Women’s (proteins found in the body’s immune cells and some cancer Health Division of Gynecologic Oncology, was the principal cells). Dostarlimab helps the body’s immune system in its investigator of a national study of the drug dostarlimab fight against cancer cells by blocking this pathway. (Jemperli) developed by GlaxoSmithKline LLC. Led by Dr. Bradford, the gynecological oncology research team Women with advanced and recurrent endometrial cancer including Kelley Qualters, Research Nurse Coordinator, have limited therapeutic options and have a very poor participated in the GARNET Trial, a study in patients prognosis, but dostarlimab presents an exciting and effective with advanced solid tumors, including endometrial cancer. option, with 42.3% of patients achieving a complete Results of this trial led to the FDA approval in April of response (disappearance of tumor) or a partial response dostarlimab for treating patients with recurrent or advanced (shrinkage of tumor) to treatment. In addition, this response endometrial cancer that has progressed on or following is durable — for 93% of responders, the response lasted for prior treatment with a platinum-containing chemotherapy six months or more. and whose cancers have a specific genetic feature known as dMMR (which contain abnormalities that affect the The following team members were involved in this proper repair of DNA inside the cell). Dostarlimab works landmark trial: Drs. Bradford, Darus, Lachance, Small by targeting the cellular pathway known as PD-1/PD-L1 and Soultanakis, as well as Research Coordinators Lynne Lohner and Robin Donovan. NEW MEDICAL DIRECTOR’S ROLE FOR CLINICAL TRIALS OFFICE In September, Leslie Bradford, MD, of Maine Medical Partners’ Women’s Health Division of Gynecologic Oncology, joined the Clinical Trials office in a new role as Medical Director. In this new role she is working closely with the Director of the Clinical Trials Office, Krista Garrison, MPH, CCRP, to help clinicians understand the requirements of being a Principal Investigator of a Clinical Trial and to act as a guide to their success. Since joining Maine Medical Center in 2017, Dr. Bradford has successfully mentored numerous medical students, residents and nurses in both research Leslie Bradford, MD and career development. She serves on the Education Committee for the Society of Gynecologic Oncologists and the International Gynecology Cancer Society. Her research areas include international and local projects related to exploring and optimizing care delivery to underserved populations, which in Maine relates to gynecologic cancer care-delivery in rural locations, the impact of overweight/obesity on cancer care outcomes, HPV vaccination in rural settings and international cervical cancer screening programs. 2021 YEAR IN REVIEW 30

CLINICAL RESEARCH & CLINICAL TRIALS MAINE HEALTH CANCER CARE NETWORK Expanding Cancer Care Research, Education, & Treatment for Patients in Maine MaineHealth Cancer progress have included: Care Network (MHCCN) was awarded a six-year $5.1 facilities expansion, million dollar grant to join the NCI Community telehealth advancement, Oncology Program (NCORP) in 2019. Today, patient education, and this grant spans the spectrum of the cancer treatment innovations. care continuum from prevention, screening, One example of a recent therapeutic, quality-of-life, to end-of-life and cancer treatment innovation was care delivery research for patients across Maine WALDO COUNTY GENERAL the addition of a FDA- and the Mt. Washington HOSPITAL, BELFAST approved personalized Valley in New Hampshire. PEN BAY MEDICAL CENTER, immunotherapy treatment The NCORP support for ROCKPORT for prostate cancer patients oncology research program at Stephens Memorial has been vital in helping FRANKLIN COMMUNITY HEALTH MaineHealth create NETWORK, FARMINGTON additional infrastructure to support research LINCOLNHEALTH, DAMARISCOTTA Hospital. This type of initiatives throughout the network and offers a robust research arm in partnership with WESTERN MAINE HEALTH, treatment allows patients Maine Medical Center Research Institute. The number of NORWAY to receive state-of-art care, clinical trials available to oncology patients in the network is expected to nearly triple over the next five years. MAINEGENERAL MEDICAL without having to travel to CENTER HAROLD ALFOND CENTER a major metropolitan area. Despite the challenges from the COVID-19 pandemic over the past two years, the MHCCN continues to grow and the FOR CANCER CARE, AUGUSTA Another exciting network teams continue to meet the needs of patients and MID COAST HOSPITAL, MHCCN initiative that communities. Some factors that have contributed to this BRUNSWICK MAINE MEDICAL CENTER, PORTLAND ST. MARY’S REGIONAL has expanded this year is MEDICAL CENTER, LEWISTON the National Institutes of Health NCI Moonshot MEMORIAL HOSPITAL, NORTH CONWAY, NH SOUTHERN MAINE BioBank program. The HEALTH CARE, BIDDEFORD program consists of a network of seven hospitals serving a large, mainly rural population throughout the state of Maine and portions of New Hampshire, including several hard-to-reach island communities. Anne Breggia, PhD, Director of the Maine Medical Center BioBank is the Principal Investigator on the Moonshot program which seeks to collect longitudinal blood and tissue samples from 1,000 oncology research participants over five years. 31 MAINE MEDICAL CENTER RESEARCH INSTITUTE

Last year NCORP was rural populations, and to selected as one of three develop resources to address Biospecimen Source Sites these barriers along with and was awarded local Cancer patients often feel that to get state-of-the-art care and to recruitment strategies. KMttteuudaohhnnsinoviiiedgsdnesreausselgrewgefpesrteetaenorphhlmdedro,ncepkteroii.r,MpctnnherTMtCmvosoDehefrvaDiuns,tiinntsdnt,oiocMeegcdferaddaoiirnSBttnmeioidMciegnnorp,s.gsoNbeScaaaoatolneugirinntniendeeliksmvihrcepeouanaftrlutareahBrtnlnrfoeieiurpmdcosaonieoibe.lpnldapTaa—igriounnnncdlwwkchtgaalsh’t.iays,tniesooMoiiarcnnemuiwamavcrsloeailptutnrrdrratiktdeeaoathHiildweesnariyneveittgthtilaachioserrvilntlayuehsahc.iaainbttilveealileeayessl,dactocetrecpasreaanxsrs—novidetsejcoaetSloeircatcrvncotodeshgtAavurCastpcmde.enopveRaacloiemejltsormadhotr,bericmgacoyarwkneror,BdoetauMrotrocpoikDaplosto.r,o,hndsFloeAiestnwr.CatcPnhosTotoahloskiegseihmTlrashetuodovesalvr,emmdsaoprealibecarngeatesoiictcrenplnsytnughacrtgdrpeesorte,spanolemdrorueteggrenpcsoiymeeosnanrnlgbapssthvne,trrersoidaepsinctgdsoeoitinowifsitrchntgaeihetreachaseertl, help identify barriers to Biobank participation within their For more information on how you might be able to participate in a clinical trial, visit mainehealth.org/cancer. 2021 YEAR IN REVIEW 32

RESEARCH TRAINING & CAREER DEVELOPMENT Maine Medical Center Research Institute is composed of basic and clinical research laboratories and health services research that support the research training of scientists, and scientists-in-training (postdoctoral fellows, graduate students, and undergraduate students), physicians and medical trainees (residents, medical students). This year there were several notable awards for junior faculty. GRADUATE STUDENTS GET A LEG UP WITH ADDITIONAL AWARDS Two Universit y of Maine In April Katie Stieber, a Graduate School of Biomedical graduate student in Dr. Lucy Science and Engineering Liaw’s lab, was awarded a students received awards that National Institutes of Health’s will support and further their predoctoral fellowship from the research at MMCRI. In February National Heart Lung and Blood Connor Murphy, Connor Murphy, a graduate Katie Stieber, Institute to support her thesis Graduate Student, student in Dr. Michaela Reagan’s Graduate Student, research. Katie is interested in Regan Lab lab, received a 3-year mentored Liaw Lab perivascular adipose tissue and predoctoral fellowship award. how it influences cardiovascular This award from the National Cancer Institute was for his disease progression. The title of her F31 fellowship award is proposal entitled, “Lipid metabolism-driven drug resistance “Rab27a functions in the vascular microenvironment”. in multiple myeloma”. Connor will study the mechanisms by which bone marrow adipocytes and fatty acid oxidation affect cell survival and the development of drug resistance in multiple myeloma tumor cells. Education & Training Fast Facts: 6 8 23 Master’s Students Post-D Researc PhD Students 33 MAINE MEDICAL CENTER RESEARCH INSTITUTE

CAREER DEVELOPMENT Eric Anderson PhD, Faculty Matthew Lynes PhD, joined the Scientist I, was awarded a Tufts Center for Molecular Medicine Clinical and Translational Science as a Faculty Scientist I in August. Institute career development Dr. Lynes brings with him a (KL2) award this summer for his Mentored Research Scientist work entitled, “Cancer patients’ Career Development Award from expectations for genomic tumor the National Institute of Diabetes Eric Anderson, PhD testing.” Dr. Anderson will Matthew Lynes, PhD and Digestive and Kidney Faculty Scientist conduct research to characterize Faculty Scientist Diseases (NIDDK), also known patients’ expectations for genomic as a K01. The K01 provides an tumor tests and how they match with actual clinical outcomes. intensive, supervised, research and career development He is focusing on rural, disadvantaged patients who may have experience for nonclinical, doctoral researchers as they low knowledge and high expectations for genomic tumor transition to independent research careers. Using this funding testing. He will also receive training and mentoring from a Dr. Lynes has been evaluating how lipid hormones signal multi-disciplinary mentorship team. The goal of the Tufts in fat tissue to regulate metabolism. Lipid hormones are an CTSI Career Development Award Program is to train the next emerging class of molecules that are affected by obesity, and an generation of highly successful translational scientists in the increased understanding of the role that they play in regulating concepts of team science and in translating research findings metabolism may improve our ability to treat metabolic into clinical practice, public health, and public policy. Selected dysfunction. Dr. Lynes has recently joined the COBRE in scholars receive salary support and fringe benefits for two years Metabolic Networks at MMCRI. For more information on of protected research training time. the COBRE in Metabolic Networks see page 21. 8 18 31 octoral h Fellows Medical Students Academic interns, over 16 Labs & Research Areas 2021 YEAR IN REVIEW 34

RESEARCH TRAINING & CAREER DEVELOPMENT A CAREER PATHWAY THROUGH MMCRI Amanda Lessard, PhD, first Engineering. She earned her PhD in Cell and Molecular Biology in 2015, and transitioned to a Research Fellow in joined Maine Medical Center Dr. Doug Sawyer’s lab at MMCRI shortly afterward. “My experience in Dr. Sawyer’s laboratory brought me closer to Research Institute (MMCRI) translational science where I began a desire to work more closely with the clinical aspects of research,” said Dr. Lessard. in 2007 as an intern in the Fortunately, Maine Medical Center has a unique position Summer Student Research called a Research Navigator, a position that is typically held by a MPH or PhD scientist to assist clinicians with Program (SSRP). She was a rising research. In April, she became a Research Navigator to help investigators develop their research ideas into workable senior at the time majoring in protocols, assisting with compliance for human subjects’ research or data analysis and dissemination of their findings. Biochemistry at Chestnut Hill Additionally, her work with CEBO includes development of a Community Engaged Research program within Amanda Lessard, PhD College in Philadelphia, PA. MaineHealth that will bridge a collaboration between Now Dr. Lessard is a Research the research community and the Maine communities we serve. This bi-directional partnership is aimed to design Navigator within the Community Engagement, Bioethics comprehensive research programs that benefit our Maine communities’ needs. and Outreach (CEBO) Core of the Acute Care Research As explained by Dr. Lessard, “The evolution of my career and Rural Health Disparities COBRE (see page 25). She is a began with an opportunity to be part of the Summer Student Research Program and has resulted in my ability to build a prime example of the career research pathways available to career in Maine that is fulfilling a desire to positively impact the health of my community.” students at MMCRI, and students can start as early as high Take a closer look at the timeline to learn how Dr. Lessard school through the high school biomedical science series. and other students have navigated their journey in research at MMCRI. Dr. Lessard’s start in the SSRP program crystalized her desire to do research. According to Dr. Lessard, “I knew I enjoyed science at the start of my internship but I fell in love with research by the time I had to pack up and head back to college. During my senior year I kept in communication with my MMCRI mentor, Dr. Calvin Vary, about career advice and various research opportunities.” From there, Dr. Lessard went to the National Institutes of Health for 2 years as a post-baccalaureate fellow, and then returned in 2010 as a Research Technologist in Dr. Pradeep Sathyanarayana’s lab at MMCRI. He encouraged her to pursue a PhD, and in 2011 she joined the University of Maine’s Graduate School of Biomedical Science and 35 MAINE MEDICAL CENTER RESEARCH INSTITUTE

RESEARCH CAREER PATHWAY High School Summer Student Masters, Postdoctoral, Professional Biomedical Research Program, PhD, Residency, Devlopment, Science Series MD, Fellowship Academic Year Programs Research Internship, College Programs Navigation Student Internship Programs HIGH SCHOOL COLLEGE GRADUATE / POSTDOCTORAL / EARLY CAREER MEDICAL RESIDENCY / BILAN MOHAMED FELLOWSHIP Current Research High School Summer Student Accepted to MMCRI Postdoc Navigator at Program Research Program MaineTrack Medical MaineHealth School Program University of Research Southern Maine Navigation AMANDA LESSARD, PhD Summer Student UMaine PhD, Research Program MMCRI SPENCER SCOTT, MD MaineTrack Current MMC Medical School Surgery Resident Summer Student Research Program University of Southern Maine 2021 YEAR IN REVIEW 36

LOOKING FORWARD: THE FUTURE OF RESEARCH WITHIN MAINEHEALTH Putting together the Year in Review is always an opportunity to celebrate all we have accomplished but it is also a chance to consider where we are going in the next year and beyond. We have several exciting initiatives we will be working on over the next 12 months. To begin, we are excited to announce a new functional organizational chart and a new name — the MaineHealth Institute for Research — which better communicates what we do: provide services for all in MaineHealth to apply for funding, conduct research, and learn how to do rigorous research. Look for a roll-out of an official name change over the next several months. We look forward to Anne Breggia, PhD, Director of the Biobank, and Bob Carlson, MD, Medical Director of NorDx, creating a new research resource — the Center for Applied Science and Technology. The Center will provide infrastructure to enable the coordinated integration of our laboratory and clinical/data resources with NorDx’s clinical instrumentation, data resources and support services throughout the state of Maine. With resources and support from the Northern New England Clinical & Translational Research Network and the Acute Care Research & Rural Disparities Center of Biomedical Research Excellence (COBRE), we will expand our ability to collaboratively engage communities 37 MAINE MEDICAL CENTER RESEARCH INSTITUTE

H AND BEYOND and community members throughout Maine by creating Regional Community Engagement Councils. Through the councils we will learn about community priority health issues as well as get feedback and involvement in our research. We will be recruiting two leaders into research — new Directors of the Center for Molecular Medicine and the Center for Outcomes Research and Evaluation, whom we expect will bring new ideas and vision for expanding the impactful research we conduct. In addition with Dr. Lucy Liaw’s leadership, we will be convening leaders and educators who provide education on research topics and how to conduct research, so we can work together to ensure we provide comprehensive education, design new educational offerings where they are needed, and create an easy to access resource for all students, trainees, staff, and faculty. Finally, we are focused on increasing our investment in and support of our faculty and staff as well as strengthening our valuable partnerships with the Tufts Clinical and Translational Science Institute, the University of Vermont, The Roux Institute, and the MaineHealth Center for Innovation, among many others. There are many opportunities ahead for the MaineHealth Institute for Research — we welcome the future and look forward to opening new doors to improving the health of the people of Maine and beyond. 2021 YEAR IN REVIEW 38

MMCRI Research Resources Support Our Research For physicians and staff throughout the MaineHealth system, please contact the following MMCRI staff for information MMCRI is already one of the most innovative research organizations and assistance if you are interested in research projects: in the nation. RESEARCH GRANT PROPOSALS: With your help, we can achieve even more. Carolyn Elliott-Farino Director, Research Grants Services By donating to MMCRI, you help bring the latest scientific discoveries [email protected] or 207-396-8188 to the bedside and improve the quality of care patients receive. Today’s groundbreaking study could be tomorrow’s life-saving treatment. RESEARCH CONTRACTS: Your gift will help support research that furthers our understanding Colleen O’Neill of disease processes, which enables us to develop better diagnostics Research Contracts Officer and treatment. [email protected] or 207-396-8058 Areas of opportunity for support of MMCRI’s laboratory-based or COMPLIANCE & INSTITUTIONAL REVIEW BOARD: clinical research projects include: Cardiovascular Disease, Cancer, Elizabeth Kipp Campbell Metabolic Disease, Molecular Biology and Genetics, Clinical Trials, Director, Office of Research Ethics & Compliance Psychiatric Research, and Vector-Borne Diseases. [email protected] or 207-661-4472 Our efforts go beyond research, as well: by supporting our summer CLINICAL TRIALS: student scholarships, you will help us educate and cultivate the next Krista Garrison generation of researchers, and ensure that the quest for knowledge Director, Clinical Trials Office and insight continues for years to come. [email protected] or 207-396-8074 If you’re interested in supporting the work of Maine Medical RESEARCH NAVIGATION: Center Research Institute, please contact Kristen Crean of Wendy Craig the Philanthropy Department at 207-662-3895 or by email Research Navigator at [email protected]. [email protected] or 207- 662-6438 NORTHERN NEW ENGLAND CLINICAL & TRANSLATIONAL RESEARCH NETWORK: For information visit: nne-ctr.net 81 Research Drive ∙ Scarborough, ME 04074  207-396-8100 mmcri.org