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
Chief, Matrix Metalloproteinase Section
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 from 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 Matrix Metalloproteinase 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

Selected Publications

Gehron Robey, P. and Boskey, A.L. The biochemistry of bone. In Osteoporosis, Marcus, R. and Feldman, D., eds., Academic Press, In Press.

Gehron Robey, P., Fedarko, N.S. and Vetter, U.K. The role of in vitro analysis in unraveling the cause and providing the potential cure of Osteogenesis imperfecta. In Advances in Stomatology, Baum, B., ed. In Press.

Additional Publications

Riminucci M, Collins MT, Fedarko NS, Cherman N, Corsi A, White KE, Waguespack S, Gupta A, Hannon T, Econs MJ, Bianco P, Gehron Robey P 2003 FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. J Clin Invest 112(5):683-92. http://www.ncbi.nlm.nih.gov/pubmed/12952917

Kuznetsov SA, Mankani MH, Leet AI, Ziran N, Gronthos S, Robey PG 2007 Circulating connective tissue precursors: extreme rarity in humans and chondrogenic potential in guinea pigs. Stem Cells 25(7):1830-9.
http://www.ncbi.nlm.nih.gov/pubmed/17464083

Sacchetti B, Funari A, Michienzi S, Di Cesare S, Piersanti S, Saggio I, Tagliafico E, Ferrari S, Robey PG, Riminucci M, Bianco P 2007 Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131(2):324-36. http://www.ncbi.nlm.nih.gov/pubmed/17956733

Kuznetsov SA, Cherman N, Riminucci M, Collins MT, Robey PG, Bianco P 2008 Age-dependent demise of GNAS-mutated skeletal stem cells and "normalization" of fibrous dysplasia of bone. J Bone Miner Res 23(11):1731-40.
http://www.ncbi.nlm.nih.gov/pubmed/18597624

Bianco P*, Robey PG*, Simmons PJ* 2008 Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell 2(4):313-9. *These authors contributed equally. http://www.ncbi.nlm.nih.gov/pubmed/18397751

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.http://www.ncbi.nlm.nih.gov/pubmed/20590404

Robey, PG 2011 Cell sources for bone regeneration: the good, the bad, and the ugly (but promising). Tissue Eng Part B Rev, In press. http://www.ncbi.nlm.nih.gov/pubmed/21797663

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-XXXX
Bone Marrow Stromal Cell Infusion to Treat Refractory Acute Graft Versus Host Disease 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-XXXX
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