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Dr Bellur Seetharam
Research and Selected Publications

Research Interests

Vitamin B12 (Cobalamin, Cbl) absorption and transport in human 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 specific receptor, intrinsic factor-Cbl receptor (cubilin). Absorbed Cbl is bound by plasma transcobalamin II (TC II) and its cellular uptake by all cells is mediated via TC II-receptor.

Cobalamin serves a coenzyme function in key metabolic reactions, particularly in DNA synthesis. Human Cbl deficiency manifests as megaloblastic anemia, immune deficiency, gastro-intestinal and neurological disorders and can occur due to defective expression of these Cbl binding proteins and their cell surface receptors.

Projects that are currently being investigated include:

  1. Analysis of cis-elements of the human TC II promoter that play a role in its tissue-specific expression, regulated expression in some forms of cancer, and defective expression in human TC II deficiency.
  2. Structure and function relationship of TC II with respect to its Cbl and receptor binding domains.
  3. The molecular cell biology of both Cbl receptors to delineate the structural elements that are important in their ligand binding and cellular targeting of cubilin to the apical domain and of TC II-receptor to the basolateral domain, respectively, of pol arized epithelial cells.
  4. The characterization of pathways for the sorting of Cbl during its apical to basolateral transcytosis in the epithelial cell.

Selected Publications

Yammani RR, Seetharam S, Seetharam B. Cubilin and Megalin expression in the rat: Effect of thyroidectomy. Am. J. Physiol (In Press, 2001).

Said H, Rose C, Seetharam B. Intestinal absorption of water-soluble Vitamins: Cellular and Molecular aspects. Current topics in membranes. Molecular physiology of intestinal transport: Emerging Concepts. (Academic Press) 50:35-75, 2001

Seetharam B. Receptor-mediated endocytosis of cobalamin (Vitamin B12). Ann. Rev. Nutr. 19:173-195, 1999.

Li N, Seetharam B. A 69-bp pair fragment derived from human transcobalamin II promoter is sufficient for high bidirectional activity in the absence of a TATA box and an initiator element in transfected cells. Role of an E box in transcriptional activity. J. Biol. Chem. 273:28170-28177, 1998.

Bose S, Chapin SJ, Seetharam S, Feix J, Mostav, KE & Seetharam B. Brefeldin A (BFA) inhibits the basolateral membrane delivery and dimerization of transcobalamin II-receptor in human intestinal epithelial Caco-2 cells. J. Biol. Chem. 273, 16163-16169, 1998.

Li N, Seetharam S, Seetharam B. Characterization of human transcobalamin II promoter: A PROXIMAL GC/GT BOX IS A DOMINANT NEGATIVE ELEMENT. J. Biol. Chem. 273:16104-16111, 1998.

Last modified on: Monday, 13-Oct-2003 16:33:50 CDT

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