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Pamela Gehron Robey, Ph.D.

Pamela Gehron Robey, Ph.D.Chief, Craniofacial and Skeletal Diseases Branch, DIR
Co-Coordinator, NIH Bone Marrow Stromal Cell Transplantation Center
Chief, Skeletal Biology Section, CSDB, DIR
Acting Scientific Director, NIH Stem Cell Unit

NATIONAL INSTITUTES OF HEALTH/NIDCR
BUILDING 30 ROOM 228
30 CONVENT DR MSC 4320
BETHESDA MD 20892-4320

Phone: (301) 496-4563
Fax: (301) 402-0824
E-mail: Dr. Pamela G. Robey

Research Interests/Scientific Focus

The Skeletal Biology Section has a long-term interest in defining the biological properties of post-natal skeletal stem cells (SSCs), which are a multipotent subset of bone marrow stromal cells (BMSCs), with a particular emphasis on determining the role that they play in the pathophysiology of skeletal diseases, and how they can be used in tissue engineering and regenerative medicine. It has been our hypothesis that any genetic defect (intrinsic factor) or change in the microenvironment (extrinsic factor) that alters the biological activity of skeletal stem cells, which are central mediators of post-natal skeletal metabolism, will cause skeletal abnormalities. Furthermore, based on the remarkable ability of skeletal stem cells to regenerate a complete bone/marrow organ, a major goal is to further develop our techniques for bone regeneration in human patients with skeletal defects, and to expand the possible utilization of these cells for non-skeletal applications, due to their immunomodulatory effects. In addition, the SBS has recently started to develop the techniques for osteogenic and chondrogenic differentiation of human pluripotent stem cells (human embryonic and induced pluripotent stem cells), as another potential source of cells for tissue engineering.

The scientific goals of the Connective Tissue Remodeling Section are to define the role of matrix remodeling in general, and collagen remodeling in particular, in health and disease. These functions are investigated by generating animal models with various types of MMP deficiency, followed by in depth-analyses of the mechanisms by which the phenotypes are generated. In particular, the MMPS is focused on MT1-MMP, a membrane bound type of MMP, due to the fact that its global depletion results in a severe skeletal phenotype, characterized by craniofacial dysmorphology and dwarfism, due to defects in both bone formation and in bone resorption. Furthermore, there is a hematopoietic defect in the MT1 deficient mouse, due in part to the inability of MT1-deficient osteogenic cells to provide an appropriate hematopoietic microenvironment.  Current studies have employed mouse genetics to delete MT1 activity from osteogenic cells at different stages of maturation, and in the hematopoietic lineage, which gives rise to osteoclasts. Interestingly, the cell-specific MT1-deficient models exhibit different skeletal phenotypes, highlighting the complexity of MT1’s action on the skeleton as a whole. The mechanism of action of MT1 in different skeletal cell types is under investigation.

Biographical Sketch

1974 B.A., Biology, Susquehanna University, Selinsgrove, PA
1977 M.S., Biochemistry, Catholic University of America, Washington, D.C.
1979 Ph.D., Cell Biology, Catholic University of America, Washington, D.C.
1974-1979 Biological Aide, Laboratory of Developmental Biology and Anomalies,  NIDR, NIH
1979-1980 Individual National Research Service Awardee, Genetics and Biochemistry Branch, NIAMD, NIH
1981-1983 Staff Fellow, Retinal and Ocular Connective Tissue Diseases Section, NEI, NIH
1983-1987 Senior Staff Fellow, Mineralized Tissue Research Branch, NIDR, NIH
1987-1992 Research Biologist, Bone Research Branch, NIDR, NIH
1992-1996 Section Chief, Skeletal Biology Section, Bone Research Branch, NIDR, NIH
1994-1996 Chief, Bone Research Branch, NIDR, NIH
1994-1996 Acting Chief, Skeletal Clinical Studies Unit, Bone Research Branch, NIDR, NIH
1997-date Chief, Craniofacial and Skeletal Diseases Branch, NIDCR, NIH
1997-date Chief, Skeletal Biology Section, Craniofacial and Skeletal Diseases Section, NIDCR, NIH
1997-2005 Acting Chief, Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, NIDCR, NIH
2004 Acting Scientific Director, NIDCR, NIH
2004-2010 Acting Chief, Matrix Metalloproteinase Unit, Craniofacial and Skeletal Diseases Branch, NIDCR, NIH
2005 Acting Deputy Director, DIR, NIDCR, NIH
2008 - Present Co-coordinator, NIH Bone Marrow Stromal Cell Transplantation Center 
2010 - Present Acting Scientific Director, NIH Stem Cell Unit
2011-date Chief, Matrix Metalloproteinase Section, Craniofacial and Skeletal Diseases Branch, NIDCR, NIH

Selected Publications

Skeletal Biology Section:

  1. Bianco P, Cao X, Frenette PS, Mao JJ, Robey PG, Simmons PJ, Wang CY* 2013 The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine. Nat Med 19(1):35-42. *Authors are in alphabetical order.
  2. Kuznetsov SA, Cherman N, Robey PG 2010 In vivo bone formation by progeny of human embryonic stem cells. Stem Cells Dev 20(2):269-87.
  3. Chou DB,* Sworder B,* Bouladoux N, Roy CN, Uchida AM, Grigg M, Robey PG,** Belkaid Y** 2012 Stromal-derived IL-6 alters the balance of myeloervthroid progenitors during Toxoplasma gondii infection. J Leukoc Bio1 92(1):123-131. *Co-first authors, **Co-correspoding authors.
  4. Balakumaran A, Pawelczyk E, Ren J, Sworder B, Chaudhry A, Sabatino M, Stroncek D, Frank JA, Robey PG 2010 Supemaramagnetic iron oxide nanoparticles labeling of bone marrow stromal (mesenchymal) cells does not affect their "sternness." PLoS One 5:e11462.
  5. Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters K, Turner J, Cannons JL, Bick D, Blakemore L, Blurnhorst C, Brockmann K, Calder P, Cherman N, Deardorff MA, Everman DB, Golas G, Greenstein RM, Kato BM, Keppler-Noreuil KM, Kuznetsov SA, Miyamoto RT, Newman K, Ng D, O'Brien K, Rothenberg S, Schwartzentruber DJ, Singhal V, Tirabosco R, Upton J, Wientroub S, Zackai EH, Hoag K, Whitwood-Neal T Robey, PG, Schwartzberg PL, Darling TN, Tosi LL, Mullikin JC, Biesecker LG 2011 A mosaic activating mutation in AKTl associated with the Proteus syndrome. N Engl J Med 365(7):611-619.

Connective Tissue Remodeling Section:

  1. Szabova L, Yamada SS, Wimer H, Chrysovergis K, Ingvarsen S, Behrendt N, Engelholm LH, Holmbeck K 2009 MTI-MMP and type II collagen specify skeletal stem cells and their bone and cartilage progeny. J Bone Miner Res24(11):1905-16.
  2. Markovic DS, Vinnakota K, Chirasani S, Synowitz M, Raguet H, Stock K, Sliwa M, Lehmann S, Kalin R, van Rooijen N, Holmbeck K, Heppner FL, Kiwit J, Matyash V, Lehnardt S, Kaminska B, Glass R, Kettenmann H. 2009 Gliomas induce and exploit microglial MTI-MMP expression for tumor expansion. Proc Natl Acad Sci USA 106(30):12530-5.
  3. Makareeva E, HanS, Vera JC, Sackett DL, Holmbeck K, Phillips CL, Visse R, Nagase H, Leikin S. 2010 Carcinomas contain a matrix metalloproteinase­ resistant isoform of type I collagen exerting selective support to invasion. Cancer Res70(11):4366-74.
  4. Szabova L, Son MY, Shi J, Sramko M, Yamada SS, Swaim WD, Zerfas P, Kahan S, Holmbeck K. 2010 Membrane-type MMPs are indispensable for placental labyrinth formation and development. Blood 116(25):5752-61.
  5. Ingvarsen S, Porse A, Erpicum C, Maertens L, Jurgensen HJ, Madsen DH, Melander MC, Gardsvoll H, Heyer-Hansen G, Noel A, Holmbeck K, Engelholm LH, Behrendt N Targeting a single function of the multifunctional matrix metalloprotease MTI-MMP: impact on lymphangiogenesis. J Bioi Chem 288(15):10195-204. 
      

Clinical Trials

 

  • 00-D-0184
    Evaluation and Treatment of Skeletal Diseases
    Michael T Collins, MD, PI, Tenure Track Investigator, Craniofacial and Skeletal Diseases Branch, NIDCR
    Pamela Gehron Robey, PhD, AI, Skeletal Biology Section, Craniofacial and Skeletal Diseases Branch, NIDCR
  • 10-CC-0053
    Collection of Bone Marrow from Healthy Volunteers and Patients for the Production of Clinical Bone Marrow Stromal Cell (BMSC) Products
    David F. Stroncek, MD, PI, Cell Processing Section, Department of Transfusion Medicine, CC
    Pamela Gehron Robey, PhD, LAI, Skeletal Biology Section, Craniofacial and Skeletal Diseases Branch, NIDCR
  • 12-H-0010
    A Phase 1 Study of Bone Marrow Stromal Cell Infusions to Treat Acute Graft Versus Host Disease, Marrow Failure and Tissue Injury after Allogeneic Stem Cell Transplantation
    Minoo Battiwalla, MD, PI, Hematology Branch, NHLBI
    Pamela Gehron Robey, PhD, AI, Skeletal Biology Section, Craniofacial and Skeletal Diseases Branch, NIDCR
  • 12-H-0078
    Preliminary Assessment of Direct Intra-myocardial Injection of Autologous Bone Marrow-derived Stromal Cells on Patients Undergoing Revascularization for CAD with Depressed Left Ventricular Function
    Pamela Gehron Robey, PhD, PI, Skeletal Biology Section, Craniofacial and Skeletal Diseases Branch
    Keith Horvath, MD, LAI, Cardiothoracic Surgery Research Program, NHLBI

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This page last updated: September 07, 2016