Investigators

Thomas O. Carpenter, MD

(Please see Administration page for biographical information.)

Marie Demay, MD

Marie Demay is Professor of Medicine at Harvard Medical School and a physician at Massachusetts General Hospital. Her research has focused on the actions of 1,25-dihydroxyvitamin D at cellular, molecular and whole organism levels, as well as investigating factors that modulate osteoblast differentiation.

Dr. Demay's interest in rachitic and hypophosphatemic disorders developed during her work with a mouse model of Hereditary Vitamin D Resistant Rickets engineered in her laboratory. Her studies indicate that rickets occurs as a consequence of impaired apoptosis of hypertrophic chondrocytes, and that hypophosphatemia plays a key role in the etiology of this growth plate abnormality. Further studies have demonstrated that extracellular phosphate mediates apoptosis of hypertrophic chondrocytes by activating the mitochondrial apoptotic pathway.

Dr. Demay is principal investigator for the YC-XLH project, "Phosphate, PTH, and FGF23 as mediators of the rachitic growth plate."

V.P. Eswarakumar, PhD

Veraragavan P. Eswarakumar holds a dual appointment at the Yale School of Medicine as Assistant Professor in the Department of Orthopaedics and Rehabilitation and in the Department of Pharmacology.

Dr. Eswarakumar's primary research interest relates to mechanisms of signaling by fibroblast growth factors (FGFs). An important hallmark of the FGF family is that a variety of fibroblast growth factors receptor (FGFR) isoforms are generated by alternative splicing of mRNA transcripts that have distinct ligand binding specificities and tissue distribution. During development, FGFs play a critical role in morphogenesis by regulating cell proliferation, differentiation, and cell migration. In the adult organism, FGFs play an important role in the control of the nervous system, wound healing, mineral homeostasis, and tumor angiogenesis. Further, activating mutations in FGFRs have been identified in a variety of human cancers and, most relevant to the YC-XLH, skeletal disorders.

Dr. Eswarakumar's work with the Center focuses on the FGF/FGFR/klotho signaling complex as it relates to XLH. He is co-investigator, with Dr. Joseph Schlessinger, of the YC-XLH project, "The structure, function, and pharmacologic inhibition of FGF23." Dr. Eswarakumar also received a two-year YC-XLH Pilot award.

Karl L. Insogna, MD

(Please see Administration page for biographical information.)

Joseph Schlessinger, PhD, MSc

Joseph Schlessinger is the William H. Prusoff Professor, and chair, of Pharmacology. He also directs Yale's Cancer Biology Institute. In 2010, under his leadership, the department was named the top Pharmacology program among United States medical schools by the National Research Council of the National Academies.

Dr. Schlessinger has a major research interest in the cellular mechanisms of FGF receptor signaling and has made many seminal contributions to the understanding of how these receptors function. His lab first identified a family of docking proteins (FRS2) that serve as a platform for recruitment and activation of signaling proteins responsible for the diverse cellular responses to FGFs. Dr. Schlessinger's role as a translational scientist was established with the development of SU11248, a new cancer drug that has shown considerable promise in treatment of several malignancies.

As principal investigator of the YC-XLH project, "The structure, function, and pharmacologic inhibition of FGF23," Dr. Schlessinger, together with Dr. V.P. Eswarakumar, has identified important structural regions of FGF23, including identification of the critical amino acids that determine its klotho-binding properties.

Pilot Award Investigators

V.P. Eswarakumar, PhD
(Please see above for biographical information.)

Carolyn Macica, PhD
Associate Research Scientist in Medicine (Endocrinology)

Gerald Shulman, MD, PhD
George R. Cowgill Professor of Medicine (Endocrinology)
Professor of Cellular and Molecular Physiology
Investigator, Howard Hughes Medical Institute