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Developmental Biology and Genetics | Investigators/Teams

Mary Carayannopoulos, Ph.D.  

Matthew I. Goldsmith, M.D.  

Elucidating the genetic and physiologic pathways regulating growth and size remains a fundamental challenge facing biologists. Our laboratory uses the zebrafish, Danio rerio, as a genetic model to help dissect the biology of growth control. We have primarily focused on growth control in the zebrafish caudal fin. Mutants (e.g. rapunzel) have been isolated using forward genetic screens that bypass normal growth control checkpoints and result in fin overgrowth. More recently, we have also begun to explore the relationship between nutritional status and growth. Our goal is to understand how nutritional status is integrated into an overall hierarchy of growth control pathways. Finally, we are beginning to probe the diverse roles of nutrition in early embryonic growth and development.

Robert O. Heuckeroth, M.D., Ph.D.  

Our research is directed toward discovering the molecular mechanisms that control development of the enteric nervous system (ENS). The ENS is a complex network of neurons and glia within the wall of the gut that controls intestinal motility, responds to sensory stimuli from the gut, and regulates mucosal secretion and blood flow. We are using mutant mouse models to understand the role of Ret signaling, and novel molecular and genetic approaches to identify new genes that control enteric neural crest development.

Paul W. Hruz, M.D., Ph.D.  

Our research efforts are directed toward understanding facilitative glucose transport in normal and disordered glucose homeostasis. A primary effort in our laboratory is the determination of structure/function relationships within the facilitative glucose transport proteins (GLUTs). In addition, we are also investigating the in vitro and in vivo effects of HIV protease inhibitors (PIs) on GLUT function. The goal of this research is to identify the molecular mechanisms that lead HIV-infected patients receiving PIs to develop insulin resistance.

Patrick Y. Jay, M.D., Ph.D.  

Louis J. Muglia, M.D., Ph.D., Unit Leader  

The research efforts of our laboratory center on defining the role of neuropeptides produced by the hypothalamus in perinatal adaptation, reproduction, behavior and immune function. We have a long-standing interest in the control of the mammalian stress response and the critical function for glucocorticoids in maintenance of physiological homeostasis. Of ongoing interest is defining the mechanisms by which the immune system and hypothalamic-pituitary-adrenal axis interact during inflammatory stress and thymocyte selection. The second area of major interest in our laboratory is in the elucidation of the mechanism imparting normal term labor and how this mechanism malfunctions to result in preterm labor.

Joshua B. Rubin, M.D., Ph.D.  

Our laboratory is interested in defining molecular mechanisms involved in control of proliferation and differentiation of neuronal precursors during development and how these same mechanisms contribute to the development of brain tumors. Our current studies focus on the role of the chemokine receptor CXCR4 and its ligand in these processes. Our studies have recently demonstrated that CXCR4 is critical to the progression of diverse brain malignancies and provide a scientific rationale for clinical evaluation of CXCR4 antagonists in treating both adults and children with malignant brain tumors.

David A. Rudnick, M.D., Ph.D.  

Our laboratory is interested in understanding the molecular signaling mechanisms that underlie the remarkable regenerative potential of the liver. In addition to liver mass being precisely regulated with respect to animal size in health, the liver is also able to regenerate the anatomic and functional deficits incurred by many forms of injury or disease (e.g. toxin exposure, trauma, infection). We have used partial hepatectomy in mice treated with pharmacological modulators or genetic manipulation of various signal transduction pathways to further elucidate the signaling mechanisms at work during regeneration. Ultimately, we hope these efforts lead to the development of novel therapeutic interventions to prevent or reverse the outcomes of chronic liver disease in pediatric patients.

Scott Saunders, M.D., Ph.D.  

Research in our laboratory is focused on understanding the role of heparan sulfate proteoglycans in the control of cellular responses to components of the extracellular space during development. Heparan sulfate proteoglycans represent a unique class of developmentally regulated glycoproteins that bind to and regulate a wide range of extracellular proteins, including growth factors and their binding proteins, structural extracellular matrix proteins, proteases and protease inhibitors. Our efforts have centered on analysis of glypican-3, a cell surface heparan sulfate proteoglycan expressed widely during vertebrate development. Loss of function mutations in the glypican-3 gene in humans causes Simpson Golabi Behmel syndrome (SGBS), a disorder associated with both pre- and postnatal overgrowth, a predisposition to certain childhood cancers, and a complex assortment of congenital defects including skeletal abnormalities.

Bradley T. Thach, M.D.  

Our laboratory studies infant apnea, development of control of breathing, Sudden Infant Death Syndrome, and infant sleep physiology regulation of breathing during hypoxia using both animal models and human studies. Recently, we have also undertaken epidemiologic studies related to sudden unexpected deaths in infants.

Zsolt Urban, Ph.D.  

David B. Wilson, M.D., Ph.D.  

Our laboratory investigates the role of transcription factors in differentiation, development and oncogenesis. Our work centers on the GATA-binding proteins, a group of zinc finger transcription factors implicated in lineage commitment. We have shown that GATA-4 expression in extraembryonic endoderm is essential for ventral morphogenesis in the mouse, and expression of this factor in foregut endoderm is required for proper differentiation of gastric epithelium. Current efforts are aimed at identifying novel target genes for GATA-4 and studying the interaction of this protein with other transcription factors.