Michaela Reagan, PhD

Michaela Reagan, PhD 2017-09-15T15:05:35+00:00

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

Dr. Reagan’s work will be featured in the Journal of Cellular Physiology’s December 2017 Issue

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

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.

Carolyne Falank, PhD

Research Fellow
cfalank@mmc.org

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. In addition, I will help with other projects in the characterization and discovery of how cells in the bone marrow niche work in the progression of Multiple Myeloma.  Learn more about Dr. Falank’s research.

 Mariah Farrell

Research Assistant
Mariah.Farrell@maine.edu

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.

Alumni

Katherine Bonawitz, BS

Research Associate I
katherine.bonawitz@maine.edu

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.

Sadie Tirrell

Intern
sadie.tirrell@gmail.com

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

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, International Bone and Mineral Society
  • Member, American Society of Hematology
  • Member, American Society of Bone and Mineral Research (ASBMR)
  • Member, American Society of Clinical Oncology (ASCO)
  • Member, American Association of Cancer Research (AACR)