Bellur Seetharam, Ph.D.
Professor
Dr. Seetharam obtained his Bachelors degree in Chemistry and Physics, and his Master's and Doctoral degree in Biochemistry from Bangalore University, India. After two years of postdoctoral work at the University of New Mexico and 14 years on faculty of Washington University in St. Louis, he moved to Medical College of Wisconsin in 1988 as Professor of Medicine (Gastroenterology) and Biochemistry. His research work in the past 25 years has focused on the molecular and cell biology of Vitamin B12 binding proteins and their cell surface receptors in normal and Vitamin B12 deficiency state.
Contact Information
Phone: (414)384-2000X 41566
Fax: (414) 382-5374
seethara@mcw.edu
Research Interests
Vitamin B12 (Cobalamin, Cbl) is an essential micronutrient required for red cell formation and a healthy nervous system. Its absorption and transport is regulated by two receptor mediated events. Dietary Cbl bound to a gastric protein, intrinsic factor, is endocytosed by the intestinal epithelial cells via a multipurpose receptor,cubilin, a 460 kDa protein that lacks transmembrane and cytoplasmic domains and contain a continuous stretch of 27-CUB domains. Membrane trafficking of Cubilin is dependent on escort proteins, a 55 kDa cysteine rich transmembrane protein encoded by the amnion gene (AMN) and a 600 kDa giant endocytic receptor, megalin. Absorbed Cbl bound to plasma transcobalamin (TC) is taken up by all cells via TC-receptor whose levels are tightly regulated by intracellular Cbl levels.
Projects that are currently being investigated include:
a. Mapping interactive domains of cubilin with AMN and megalin
b. Post translational modifications, membrane interactions and lipid-raft locations of cubilin
c. Molecular and cellular mechanisms of human transcobalamin receptor regulation in health and disease states such as inflammation and cancer.
Selected Publications
Identification and characterization of two distinct ligand binding regions of cubilin. Yammani RR, Seetharam S, Seetharam B. J Biol Chem. 276(48):44777 84 (2001).
Loss of albumin and megalin binding to renal cubilin in rats results in albuminuria after total body irradiation. Yammani RR, Sharma M, Seetharam S, Moulder JE, Dahms NM, Seetharam B. Am J Physiol Regul Integr Comp Physiol. 283:R339 R346 (2002).
Cobalamin transport proteins and their cell-surface receptors. Seetharam B, Yammani RR. Expert Rev Mol Med. 13;1-18 (2003).
Function and stability of human transcobalamin II: role of intramolecular disulfide bonds C98-C291 and C147-C187. Kalra S, Li N, Seetharam S, Alpers DH, Seetharam B Am J Physiol Cell Physiol. 285:C150-C160 (2003).
Transcobalamin receptor interacts with megalin in the renal apical brush border membrane. Yammani RR, Seetharam S, Dahms NM, Seetharam B. J Membr Biol. 193: 57-66 (2003).