Research & Publications
My laboratory studies the mechanisms and effects of calcium signals in polarized epithelia. One aspect of our work is to define how calcium signals are differentially regulated in the nucleus and cytoplasm. This involves identification of distinct calcium stores and release mechanisms in the nucleus, and we are examining whether and how these are activated selectively by growth factors. The second aspect of our work is to examine how calcium waves and other calcium signals regulate secretion in polarized epithelia. Calcium waves preferentially begin in, the apical region of most secretory epithelia, and we are in the process of defining the mechanisms responsible for this. We also are using an adenoviral antisense approach to understand the relative roles of each IP3 receptor isoform in regulating calcium signaling and secretion in vitro and in vivo. Another major focus is to examine intercellular communication of second messenger signals and to establish the mechanism by which gap junctions act in coordinating intercellular spread of Ca2+ waves in isolated pairs and triplets of cells.
Specialized Terms: Mechanisms and effects of calcium signals in polarized epithelia; Effect of spatial organization of calcium signals on organ function regulation; Factors that organize Ca2+ waves in hepatocytes; Organization and effects of Ca2+ waves in cholangiocytes; Mechanisms and effects of Ca2+ signals in the nucleus
Extensive Research Description
- NIH P01 DK57751 (PI: M.H. Nathanson) 04/01/01-04/30/21 Title: Regulation of liver by nuclear calcium signaling Goals: The major goals of this project are to determine the mechanisms by which calcium is regulated in the nucleus of hepatocytes, and to determine the functional effects of nuclear calcium signals in liver. Dr. Nathanson directs Project 1 and the Administrative and Cell Imaging cores of this PPG.
- NIH P30 DK34989 (PI: M.H. Nathanson) 09/01/84-08/31/20 (NCE pending) Title: Digestive Diseases Research Core Center (Yale Liver Center) Goals: Dr. Nathanson is Director of the Liver Center as well as of the Morphology and Administrative Core components of the Center. The major goals of the Morphology Core are to provide a multidisciplinary center where the research focus is liver structure, function and disease.
- NIH R01 DK114041 (PI: M.H. Nathanson) 02/01/18-03/31/23 Title: Ca2+ waves in hepatocytes: Mechanisms and effects Goals: The major goals of this project are to determine the mechanisms by which the type 2 InsP3 receptor regulates calcium-mediated bile secretion by hepatocytes, and to determine the role that loss or mis-localization of this receptor plays in the pathogenesis of cholestatic liver disease.
- NIH R01 DK112797 (PI: M.H. Nathanson) 09/01/17-08/31/22 Title: Molecular regulation of cholestasis in cholangiocytes. Goals: Major goals are to understand the role of type 3 inositol trisphosphate receptor function in cholestatic liver disease
- NIH T32 DK007356 (PI: M.H. Nathanson) 7/1/84-6/30/24 Title: Investigative Training in Hepatology. Goals: This training grant provides 1) laboratory research training for physicians who have completed clinical training in Gastroenterology and are in preparation for careers as independent investigators in academic Hepatology and research training for recent Ph.D. graduates to prepare them for careers as independent investigators in basic liver-related research.
Cell Nucleus; Cell Biology; Digestive System Diseases; Liver; Calcium Signaling; Hepatocytes