Michaela Reagan, PhD

Faculty Scientist I

EDUCATION

BS: Engineering, Harvey Mudd College
PhD: Biomedical Engineering, Tufts University
Postdoctoral Training: Medical Oncology, Dana-Farber Cancer Institute/Harvard Medical School

Watch Video: Cancer Community Center Presentation

Listen to Dr. Reagan’s Future Tech Podcast on Cancer and Bone Marrow Fat Cells:   Podcast

Reagan Lab

Discovering new ways to eradicate cancer cells.

Multiple Myeloma

Multiple myeloma (MM) is a blood cancer that grows predominantly within the bone marrow and, like many other bone-metastatic cancers, causes painful tissue destruction, disruption of hematopoiesis, bone fractures, and hypercalcemia. There is no cure for multiple myeloma and most patients eventually become resistant to all current therapies. Our research focuses on understanding the roles that fat cells (adipocytes), bone cells (osteoblast lineage cells), and other cells in the bone marrow niche play in mediating the progression of Multiple Myeloma. In addition to local bone marrow interactions, we are also exploring metabolic and systemic host effects that may drive myeloma disease progression and we are exploring ways to interfere in this process.  The characterization of how and why bone marrow stromal cells are altered by cancer cells is another focus in my lab. Research in these areas will contribute to the discovery of novel molecular targets and development of better therapies to affect not only cancer cells, but also tumor-associated stromal cells to impede tumor growth and cancer-induced bone disease.

To study myeloma growth in a more realistic 3D bone-like environment, our lab develops novel 3D, tissue engineering in vitro models of bone-cancer interactions (Figure 1). We use these models to interrogate host cell roles in myeloma and to better define spatial and temporal growth of MM within different niches of the BM. We also use in vivo mouse models to understand how and why myeloma grows in the bone marrow (Figure 2). Using methods such as Immunohistochemsitry, and microComputed Tomography, among many other tools and technologies, we are starting to understand more about the growth of MM within bone and its bone-destructive nature (Figure 3). We aim to better understand biological mechanisms driving MM and develop better therapies to deliver anti-cancer agents directly to the bone marrow. We also aim to identify better targets for anti-cancer therapy and better biomarkers to predict the occurrence of MM and patient progression or response.

Reagan_Fig1a

Figure 1: Left to Right: A Curious Silk worm, Silk Cocoons, a Silk Fibroid Protein Scaffold, Bone Cells on a Silk Scaffold creating a Tissue-Engineered Bone, and Myeloma Cells in Tissue-Engineered Bone.

Reagan_Fig2Figure 2: Left to Right: Mice with Tumors used to find novel cures and better treatments for Myeloma, Bone Marrow with Myeloma Tumor Cells, a uCT image of a femur with bone destruction due to Myeloma Growth.

Reagan_Fig3Figure 3: Top Left: Immunohistochemistry of Myeloma Tumor cells within bone using CD138 Antibodies. Top Right: H&E Staining of Myeloma cells in Bone Marrow of mice. Bottom Left: Example of Normal Mouse Bone Trabeculae in Femur and Bottom Right: Example of Bone Disease and Decreased Trabecular Bone within Mouse Femur.

Reagan_Lab_2a

Samantha Costa

PhD Candidate
samantha.n.costa1@gmail.com

Research Interests:  Originally from the Pittsburgh, PA area,  Samantha moved to Maine to attend the University of New England.  She graduated with a Bachelor of Science in Marine Biology with a minor in Art. Since graduation,  she has gained experience with patient care and wound care treatments.  Samantha is excited to be a part of the Reagan lab where she will be honing her skills in a laboratory setting. Samantha’s focus of research will be to investigate the correlation between Multiple Myeloma (MM) and bone marrow (BM) adipocytes and how BM adipocytes are effected in the presence of different drug therapies.

Anastasia D’Amico

Student Intern

Research Interests:  I am currently a senior at the University of Southern Maine where I have a Human Biology major, Biochemistry and Honors minor. This is my second year working in Dr. Michaela Reagan’s lab and I have thoroughly enjoyed all of the learning opportunities that have presented itself while being here. I am eager to continue learning more as I work more independently this year to better understand the relationship between adipocytes and Multiple Myeloma in the bone marrow microenvironment.

Heather Fairfield, MS

Research Associate III
hfairfield@mmc.org

Research Interests: My background is in molecular biology and Mendelian genetics with a focus in hormonal regulation of both metabolic genes and oncogenes. I am interested in the use of high-throughput sequencing (exome, whole genome, and RNA-Seq) to identify spontaneous mutations, and have been involved in the implementation of these techniques in mice. I received my B.A. in Biology from the University of Vermont studying the mouse mammary tumor virus and a M.S. in Biology from Wake Forest University investigating the regulation of the leptin gene by steroid hormones. I am very interested in the relationship between adipocytes and multiple myeloma (MM) cells within the bone marrow (BM) niche, and what potential MM-nourishing signals may be released by these BM-adipocytes. I’m also interested in the genetic characterization of MM cells: both primary, potentially initiating mutations, and secondary events that may lead to distinctive gene expression signatures and disease progression.

 Mariah Farrell

Research Assistant, Masters Candidate
MLFarrell@mmc.org

Research Interests:  As an intern in the Reagan lab, I was focused on inhibiting Multiple Myeloma (MM) from homing to the bone marrow via sialylation. MM can be shielded by the bone from various chemotherapy treatments, so if MM can be contained in the blood it may be easier to treat.­­­ After I graduated with my BS in Human Biology from University of Southern Maine in 2017, I have focused on several projects such as the effects bone marrow adipocytes have on MM and how this can trigger specific responses to drug treatments, and using carbon nanotubes as a form of delivery system in the body.

Connor Murphy

PhD Candidate
connor.s.murphy@maine.edu

Research Interests:  I am originally from Hull, Massachusetts and received my B.S from Brandeis University. At Brandeis I was mentored by Dr. Nelson Lau and I investigated PIWI-interacting RNA (piRNAs) biogenesis. Additionally, I served as a summer research fellow and later a research assistant in the laboratory of Dr. Ralph Isberg at Tufts School of Medicine, where I studied Legionella pneumophila and Yersina pseudotuberculosis pathogenesis. In the Reagan lab, I am studying the influence of bone marrow adipose tissue on multiple myeloma lipid metabolism and how this contributes to resistance to current chemotherapeutic agents directed against multiple myeloma.

Alumni

Katherine Bonawitz, BS

Research Interests: I am a recent graduate of the University of Southern Maine with a B.S. in Biology. I enjoy cycling, hiking, volunteering, and hanging out with my dog, Mikey. Academically, my interests include developmental biology and medicine. I am excited to be a part of the Reagan lab as I begin the next steps in my education and I hope to contribute to a better understanding of multiple myeloma.

Charlotte Crist

Research Interests:  I am originally from Boulder, Colorado and I am currently a senior at Tufts University studying biology. After graduation, I plan to attend medical school. During the summer of 2019, I studied the effects of oleic acid on myeloma multiple cells in the Reagan Lab. I am grateful for the mentorship I received in the Reagan Lab and I know that the skills I gained there will be vital to me as I enter the medical field.

Carolyne Falank, PhD

Research Interests: I obtained my B.S. in Marine Science at the University of Maine in Orono, Maine in 2005, my M.S. in Applied Medical Sciences from the University of Southern Maine in Portland, Maine in 2009 and my Ph.D. in Biochemistry and Molecular Biology from the University of Maine in Orono, Maine in 2015. During my graduate research, I studied the carcinogenic.  I will be focusing my research on the design of nanoparticles that will be used to deliver therapeutic drugs that target bone disease and Multiple Myeloma. These nanoparticles will facilitate drug delivery that will be tested in both in vitro and in vivo models, with the hope that this will provide more efficient and effective delivery techniques to multiple myeloma patients while impeding tumor growth in the bone.

Sophie Harris

Research Interests:  I first found my love for research in the Reagen lab when I was a summer intern through the MMCRI Summer Student Program in 2016. During this time I studied how sialylation affects the ability of multiple myeloma cells to home to the bone marrow microenvironment. I had such an enriching experience in the Reagan lab that the following summer, after graduating from Pitzer College, I returned as a research assistant. Today, I am studying non-mutational drug resistance in cancer at University of California San Diego.

Justin Ham

Research Interests:  During my time in the lab, I was involved in making 3D scaffolds, using material derived from silk cocoons, for cell culturing. Additionally, I reviewed an article for journal entry and co-wrote a review article on the topic of 3D cell culture models as well as multiple myeloma and fatty acid metabolism. As a current third-year medical student at the University of New England, the support and guidance I received in the Reagan Lab helped me grow as a scientist and as a future physician.

Lauren Lever

Research Interests: I am currently a medical student at the University of New England & I did my undergraduate at the University of Wisconsin – Madison. I had the opportunity to join the Reagan Lab during my first two years of medical school. While there, my research focused on the interaction between myeloma and bone marrow adipocytes as well as 3D models to study the bone marrow niche. Outside of medicine and research, my passions include hiking, running, and traveling. I am very grateful to have been a part of this dynamic and innovative team of scientists.

Majdi Masarwi, PhD

Research Interests:  I received my BS in Pharmacy from Petra University, Amman, Jordan and my PhD degree in Biomedical Sciences, at the Laboratory of Molecular Endocrinology and Diabetes, Sackler Faculty of Medicine, Tel Aviv University. During my PhD research I was committed to investigating factors that limit catch-up growth after a period of food restriction in rat models. I’m pleased to be part of Dr. Reagan’s lab. During my postdoctoral research, I’ll deeply investigate the role of the Wnt signaling inhibitor Sclerostin (SOST gene) in bone marrow adipogenesis, and explore if it plays a role in mediating bone destruction and fractures in multiple myeloma disease in-vitro and in-vivo models.

Luna Soley

Research Interests:  I started out in the Reagan lab as an Academic Intern the summer after my Sophomore year of high school in 2016. I was mentored by Michaela’s postdoc, Carolyne Falank, and had the incredible opportunity to be a part of the Reagan lab’s work investigating the mechanisms through which the Bone Marrow Microenvironment contributes to myeloma progression. I got to conduct conduct co-cultures of various myeloma cell lines in conjunction with murine adipocytes, Dexamethasone, and anti-adipokine antibodies. I worked with Michaela to write a review paper on microRNAs implicated in myeloma progression during my Junior year, and learned how to genotype with Heather the following summer. I recently transferred to Bowdoin College in Brunswick, Maine, where I’m hoping to study Marine Science. I am deeply grateful to Michaela and everyone in her lab for showing me how a love of experiments and living things could be translated into meaningful and exciting work.

Sadie Tirrell

Research Interests: I am currently working toward earning my degree in Biology with a Human Concentration at the University of Southern Maine. My passions are science and art and I live locally here in Maine, as I have my whole life. I am thrilled to be a part of Dr Reagan’s research and look forward to contributing to the team as I pursue my education.

A complete list of publications can be found on My NCBI

McDonald MM, Reagan MR, Youlten SE, Mohanty ST, Seckinger A, Terry RL, Pettitt JA, Simic MK, Cheng TL, Morse A, Le LMT, Abi-Hanna D, Kramer I, Falank C, Fairfield H, Ghobrial IM, Baldock PA, Little DG, Kneissel M, Vanderkerken K, Bassett JHD, Williams GR, Oyajobi BO, Hose D, Phan TG, Croucher PI. Inhibiting the osteocyte-specific protein sclerostin increases bone mass and fracture resistance in multiple myeloma. Blood. 2017; 129(26):3452-3464. PMID: 28515094.

Liu P, Ji Y, Yuen T, Rendina-Ruedy E, DeMambro VE, Dhawan S, Abu-Amer W, Izadmehr S, Zhou B, Shin AC, Latif R, Thangeswaran P, Gupta A, Li J, Shnayder V, Robinson ST, Yu YE, Zhang X, Yang F, Lu P, Zhou Y, Zhu LL, Oberlin DJ, Davies TF, Reagan MR, Brown A, Kumar TR, Epstein S, Iqbal J, Avadhani NG, New MI, Molina H, van Klinken JB, Guo EX, Buettner C, Haider S, Bian Z, Sun L, Rosen CJ, Zaidi M. Blocking FSH induces thermogenic adipose tissue and reduces body fat. Nature. 2017; 546(7656):107-112. PMID: 28538730.

Soley L, Falank C, Reagan MR. MicroRNA Transfer Between Bone Marrow Adipose and Multiple Myeloma Cells. Current osteoporosis reports.  2017; 15(3):162-170. PMID: 28432594.

Fairfield H, Rosen CJ, Reagan MR. Connecting Bone and Fat: The Potential Role for Sclerostin.Current molecular biology reports. 2017; 3(2):114-121. NIHMSID: NIHMS869329 PMID: 28580233 PMCID: PMC5448707.

Sacco A, Kawano Y, Moschetta M, Zavidij O, Huynh D, Reagan MR, Mishima Y, Manier S, Park J, Morgan E, Takagi S, Wong KK, Carrasco R, Ghobrial IM, Roccaro AM. A novel in vivo model for studying conditional dual loss of BLIMP-1 and p53 in B-cells, leading to tumor transformation.  American journal of hematology. 2017; PMID: 28474779.

McDonald MM, Fairfield H, Falank C, Reagan MR. Adipose, Bone, and Myeloma: Contributions from the Microenvironment. Calcified tissue international. 2017; 100(5):433-448. NIHMSID: NIHMS858417. PMID: 27343063. PMCID: PMC5396178.

Fairfield H, Falank C, Harris E, Demambro V, McDonald M, Pettitt JA, Mohanty ST, Croucher P, Kramer I, Kneissel M, Rosen CJ, Reagan MR. The skeletal cell-derived molecule sclerostin drives bone marrow adipogenesis. Journal of cellular physiology. 2017; PMID:  28460416

Glavey SV, Naba A, Manier S, Clauser K, Tahri S, Park J, Reagan MR, Moschetta M, Mishima Y, Gambella M, Rocci A, Sacco A, O’Dwyer ME, Asara JM, Palumbo A, Roccaro AM, Hynes RO, Ghobrial IM. Proteomic characterization of human multiple myeloma bone marrow extracellular matrix. Leukemia. 2017;  PMID: 28344315

Goldstein RH*, Reagan MR*, Anderson K, Kaplan DL, and Rosenblatt M. Human bone marrow-derived MSCs can home to orthotopic breast cancer tumors and can promote bone metastasis. *Co-first authorship. Cancer Res. 2010; 70(24):10044-50. PMCID: PMC3017423.

Reagan MR, Kaplan DL. Concise review: Mesenchymal stem cell tumor-homing: detection methods in disease model systems. Stem Cells. 2011; 29(6):920-7. PMID: 21557390.

Reagan MR, Seib P, Sage E, McMillin D, Janes S, Mitsiades C, Kaplan DL. Cell-Based Anti-Cancer Implant Systems: TRAIL-Mesenchymal Stem Cells and Silk Scaffolds. J Breast Cancer. 2012;15(3):273-82. PMCID: PMC3468780.

Reagan, MR and Ghobrial IM. Multiple Myeloma-Mesenchymal Stem Cells: Characterization, Origin, and Tumor-Promoting Effects. Clin Cancer Res. 2012; 18(2):342-9. PMCID: PMC3261316.

Roccaro A, Sacco A, Maiso P, Azab A, Tai Y, Reagan MR, Azab F, Flores L, Campigotto F, Weller E, Anderson KC, Scadden D, Ghobrial I. Bone marrow mesenchymal stromal cell-derived exosomes support multiple myeloma pathogenesis. J Clin Invest. 2013;123(4):1542-55. PMCID: PMC3613927.

Glavey SV, Manier S, Natoni A, Sacco A, Moschetta M, Reagan MR, Murillo LS, Sahin I, Wu P, Mishima Y, Zhang Y, Zhang W, Zhang Y, Morgan G, Joshi L, Roccaro AM, Ghobrial IM, O’Dwyer ME.. The Sialyltransferase ST3GAL6 Influences Homing and Survival in Multiple Myeloma. Blood. 2014; Epub Ahead of print. PMID: 25061176

Swami A* & Reagan MR*, Basto P, Mishima Y, Kamaly N, Glavey S, Zhang S, Moschetta M, Seevaratnam D; Zhang Y, Liu J, Memarzadeh T, Wu J, Manier S, Shi J, Bertrand N, Lu ZN, Nagano K, Baron R, Sacco A, Roccaro AM, Farokhzad OC, Ghobrial IM. Engineered Nanomedicine for Myeloma and Bone Microenvironment Targeting. PNAS. 2014;111(28):10287-92. *Co-first authorship. PMCID: PMC4104924.

Reagan MR, Mishima Y, Glavey S, Zhang Y, Manier S, Lu ZN, Memarzadeh M, Zhang Y, Sacco A, Aljawai Y, Tai Y-T, Ready JE, Shi J, Kaplan DL, Roccaro AM, Ghobrial IM. Investigating osteogenic differentiation in Multiple Myeloma using a novel 3D bone marrow niche model. Blood. 2014; 124(22):3250-9. PMCID: PMC4239334.

Roccaro AM, Sacco A, Purschke WG, Moschetta M, Buchner K, Maasch C, Zboralski D, Zöllner S, Vonhoff S, Mishima Y, Maiso P, Reagan MR, Lonardi S, Ungari M, Facchetti F, Eulberg D, Kruschinski A, Vater A, Rossi G, Klussmann S, Ghobrial IM. SDF-1 inhibition targets the bone marrow niche for cancer therapy. Cell Reports. 2014; 9(1):118-28. PMCID: PMC4194173

Reagan MR, Liaw L, Rosen CJ & Ghobrial IM. Dynamic Interplay between Bone and Multiple Myeloma: Emerging Roles of the Osteoblast. Bone. 2015;75:161-169. PMID: 25725265

Awards

ASBMR John Haddad Award 2016

Massachusetts General Hospital Center for Skeletal Research Symposium Poster Session 2015

ASBMR Harold M. Frost Young Investigator Award 2015

The Alice L. Lee, Sun Valley Young Investigator Award 2013

Academic Appointments

  • Graduate Faculty Member, University of Maine, Orono, ME
  • Assistant Professor, Tufts University School of Medicine. Boston MA
  • Presidential Scholar, Dana Farber Cancer Institute, Boston MA

Editorial Board Activities

  • Invited journal and grant reviewer: Nanomedicine, Stem Cells, Blood, Tissue Engineering, British Journal of Haematology, Annals of Hematology, Haematologica, Prostate Cancer UK, Cancer Cell International, Cell Metabolism, PLoSOne, Bone, Marrow, BoneKEy, New England Journal of Medicine, Oncotarget.
  • Section Editor for the Bone and Cancer Section of Elsevier’s Encyclopedia on Bone Biology  (2020 Expected Publication Date)

Prior Editorial Board Activities

  • Special Issue Lead Guest Editor for Stem Cells International issue on: Cancer Stem Cells and Cancer-Associated Stem Cells.

Professional Activities

  • Member, American Society of Hematology
  • Member, American Society of Bone and Mineral Research (ASBMR)
  • Board Member 2017-2020, Advances in Mineral Metabolism (AIMM)
  • Chairperson of ASBMR’s Women in Bone and Mineral Research Committee (Read more)
  • Member, American Association of Cancer Research (AACR)

Prior Professional Activities

  • CURE (Continuing Umbrella of Research Experiences) Mentor, Dana-Farber Cancer Institute
  • Co-Chair, IBMS Young Investigator Committee
  • Member, AACR Tumor Microenvironment Working Group & AACR Women in Cancer Research
  • Scientific Program Committee Member, Herbert Fleisch Meeting Brugge, Belgium
  • AACR Committee Member, Associate Member Council (AMC)-led Fundraising Committee
  • Member, American Society of Clinical Oncology (ASCO)
  • Member, International Bone and Mineral Society