Professor (with tenure) and Vice-Chairman for Research, Medicine
School of Medicine
Professor, Physiology & Biophysics
School of Medicine
PH.D., Aston University (United Kingdom)
Pharm.D., Baghdad University (Iraq)
Phone: (562) 826-5811
Fax: (562) 826-5731
University of California, Irvine
Mail Code: 8900
Irvine, CA 92668
Physiology and pathophysiology of vitamin absorption; Molecular mechanisms/regulation of membrane transport
Recepient of: National Institutes of Health MERIT Awards (R37 DK 56061) for Consistent and Excellent Contributions to Scientific Knowledge (2009-2019); Senior Research Career Scientist Award-DVA (1996-2022); Horace W. Davenport Distinguished Award, the American Physiological Society-Gastrointestinal and Liver Section (2012); “Athalie Clarke Achievement Award” for significant contribution to medical/basic science research, the University of California-School of Medicine (2015).
The water-soluble vitamins (folic acid, thiamin, biotin, riboflavin, pyridoxine, niacin, ascorbic acid) are essential micro-nutrients for normal cellular functions,growth and development. They are involved in a variety of critical metabolic reactions, and thus, their deficiency leads to serious clinical abnormalities. Humans and other mammals cannot synthesize these micro-nutrients, and thus, must obtain them from exogenous sources via absorption in the intestine. In addition, the human body has a limited capacity to store these micro-nutrients, and thus, rely heavily on efficient absorption in the intestine, and on efficient salvaging (reabsorption) in the kidney. Thus, the intestine and the kidney play central role s in maintaining and regulating normal body homeostasis of these vitamins. Because of that, and since variety of conditions are known to affect intestinal and renal transport of these micro-nutrients (e.g., genetic defects, certain disease conditions, alcohol, drug-interactions, etc.), studies that are aimed at understanding the cellular/molecular aspects of the intestinal and renal transport processes of these vitamins are of significant importance.
Studies in our laboratory over the past twenty five years have characterized many of aspects of the cellular/molecualr mechanisms involved in the transport of these micro-nutrients in health and disease and their regulation. Our studies have ranged from molecular to whole animal integrative levels. We are currently interested in characterizing transcriptional regulation of the genes that code the membrane transporters of these vitamins, examine the cell biology of the trasnport proteins with regards to membrane targeting and intracellualr trafficking, as well as study the effects of chronic alcohol use and infection with entero-pathogenic bacteria on absorption of these nutrients.
Representative list out of 205 peer-reviewed manuscripts:
1. Connor M, Blair JA and Said HM. Secondary isotopic effects in studies using radiolabeled folate tracers. Nature 287: 253 255, 1980.
2. McCloud E, Ma TY, Grant KE, Mathis RK and Said HM. L Carnitin uptake by human intestinal epithelial cell line Caco 2: Mechansim and regulation. Gastroenterol 111: 1534 1540, 1996.
3. Nguyen TT, Dyer DL, Dunning DD, Rubin SA and Said HM. Human intestinal folate Transport: Cloning, expression and distribution of complementary RNA. Gastroenterol 112:783 791, 1997.
4. Kumar CK, Moyer MP, Dudeja PK and Said HM. A protein tyrosine kinase regulated, pH dependent carrier mediated uptake system for folate by human normal colonic epithelial cell line NCM 460. J Biol Chem 272: 6226 6231, 1997.
5. Marchant JS, Subramanian VS, Parker I and Said HM. Intracellular trafficking and membrane targeting mechanisms of the human reduced folate carrier in mammalian epithelial cells. J Biol Chem 277: 33325-33333, 2002.
6. Subramanian VS, Marchant JS, Parker I and Said HM. Cell biology of the human thiamine transporter-1 (hTHTR1): intracellular trafficking and membrane targeting. J Biol Chem 278: 3976-3984, 2003.
7. Nabokina SM, Reidling JC and Said HM. Differentiation-dependent up-regulation of intestinal thiamin uptake: cellular and molecular mechanisms. J Biol Chem 280: 32676-32682, 2005.
8. Subramanian VS, Marchant J and Said HM. Targeting and trafficking of the human thiamine transporter-2 (hTHTR2) in epithelial cells. J Biol Chem 281: 5233-5245, 2006.
9. Ashokkumar B, Kumar JS, Hecht GA and Said HM. Enteropathogenic Escherichia coli inhibits intestinal vitamin B1 (thiamin) uptake: Studies with human-derived intestinal epithelial Caco-2 cells. Am J Physiol 297: G825-33, 2009.
10. Reidling JC, Lambrecht N, Kassir M and Said HM. Impaired Intestinal Vitamin B1 (Thiamin) Uptake in Thiamin Transporter-2 Deficient Mice. Gastroenterol 138:1802-1809, 2010.
11. Nabokina SM, Subramanian VS and Said HM. Association of PDZ containing protein PDZD11 with the human sodium-dependent multivitamin transporter hSMVT. Am J Physiol: GI Physiol 300: G561-567, 2010.
12. Subramanian VS, Subramanya SB and Said HM. Relative contribution of THTR-1 and THTR-2 in thiamin uptake by pancreatic acinar cells: Studies utilizing Slc19a2 and Slc19a3 knockout mouse models. Am J Physiol: GI & Liver Physiol 302: G572-578, 2011.
13. Nabokina SM, Senthilkumar SR and Said HM. Tspan-1 interacts with the thiamine transporter-1 in human intestinal epithelial cells and modulates its stability. Am J Physiol 301: G808-G8013, 2011.
14. Nabokina SM, Subramanian VS and Said HM. Effect of clinical mutations on functionality of the human riboflavin transporter-2 (hRFT-2). Mol Genet Metabol 5: 652-657, 2012.
15. Nabokina SM and Said HM. A high affinity and specific carrier-mediated mechanism for uptake of thiamine pyrophosphate (TPP) by human colonic epithelial cells. Am J Physiol: GI & Liver Physiol 303: G389-G395, 2012.
16. Biswas A, Senthilkumar SR and Said HM. Effect of chronic alcohol exposure on folate uptake by liver mitochondria. Am J Physiol 302: C203-C209, 2012..
17. Subramanian VS, Subramanya SB, Ghosal A, and Said HM. Chronic alcohol feeding inhibits physiological and molecular parameters of intestinal and renal riboflavin transport. Am J Physiol 305: C539-C546, 2013.
18. Padmanabhan S, Subramanian VS, and Said HM. Effect of the cigarette smoke component, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), on Physiological and Molecular Parameters of Thiamin Uptake by Pancreatic Acinar Cells. Plos One 8: e78853, 2013.
19. Nabokina SV, Subramanian SV, Valle JA, and Said HM. Adaptive regulation of human intestinal thiamin uptake: a role for THTR-2 transcriptional regulation. Am J Physiol 305: G593-G599, 2013.
20. Kumar JS, Subramanian VS, Kapadia R, Kashyap M and Said HM. Mammalian colonocytes possess a carrier-mediated mechanism for uptake of vitamin B3 (niacin): studies utilizing human and mouse colonic preparations. Am J Physiol 305: G207-G213, 2013.
21. Ghosal A, Lambrecht N, Subramanya SB, Kapadia R and Said HM. Conditional knockout of the Slc5a6 gene in mouse intestine impairs biotin absorption. Am J Physiol 304: G64-G71, 2013. THIS PAPER WAS SELECTED AS “EDITOR’S PICK” OF THE MONTH.
22. Ghosal A, Chatterjee N, and Said HM. Enterotoxigenic Escherichia coli infection and intestinal thiamin uptake: studies with intestinal epithelial Caco-2 cells. Am J Physiol 305: C1185 – C1191, 2013.
23. Augagneur Y, Jaubert L, Schiavoni M, Pachikara N, Garg A, Usmani-Brown S, Wesolowski D, Zeller S, Ghosal A, Cornillot E, Said HM, Kumar P, Altman S, Ben Mamoun C. Identification and Functional Analysis of the Primary Pantothenate Transporter, PfPAT, of the Human Malaria Parasite Plasmodium falciparum. J Biol Chem 288: 20558-20567, 2013.
24. Srinivasan P, Subramanian VS, Said HM. Mechanisms involved in the inhibitory effect of chronic alcohol exposure on pancreatic acinar thiamin uptake. Am J Physiol 306:G631-G639, 2014.
25. Nabokina SM, Inoue K, Subramanian VS, Valle JE, Yuasa H, and Said HM. Molecular Identification and Functional Characterization of the Human Colonic Thiamine Pyrophosphate Transporter. J Biol Chem 289:4405-4416, 2014.
Representative Invited Reviews and Book Chapters:
1. Said HM. Recent advances in carrier-mediated absorption of water-soluble vitamins. Ann Review Physiol 66: 419-446, 2004.
2. Said HM and Seetharam B. Intestinal absorption of water-soluble vitamins. In: Physiology of the Gastrointestinal Tract. Edited by Leonard R. Johnson, Kim Barrett, Fayez K. Ghishan, Juanita L. Merchand, Hamid M. Said and Jackie D. Wood; 4th Edition, Elsevier Press; San Diego; pp 1791-1826, 2006.
3. Said HM and Mohammed ZM. Intestinal absorption of water-soluble vitamins: an update. Curr Opin Gastroenterol 22(2): 140-146, 2006.
4. Said HM. Intestinal absorption of water-soluble vitamins in health and disease. Biochem J 437: 357-72, 2011.
5. Said HM and Ross C. Riboflavin. In: Modern Nutrition in Health and Disease Modern Nutrition in Health and Disease. ROSS C, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, editors; 11th edition, pp 325-330, 2011.
6. Said HM and Nexo E. Intestinal absorption of water-soluble vitamins. In: Physiology of the Gastrointestinal Tract. Edited by Johnson LR, Ghishan FK, Merchand JL, Said HM and Wood JD; 5th Edition , Elsevier Press; San Diego; pp 1711 – 1756, 2012
7. Said HM. Recent advances in transport of water-soluble vitamins in organs of the digestive system: a focus on the colon and the pancreas. Am J Physiol: Gastrointest Liver Physiol, invited review (In press, 2013). THIS REVIEW WAS SELECTED AS “EDITOR’S PICK” OF THE MONTH
8. Said HM and Trebble T. Intestinal digestion and absorption of micronutrients. In: Slesenger and Fordtran Gastrointestinal and Liver Disease; Feldman M, Friedman LS, and Brandt LJ, editors; Elsevier publishing (In press, 2013).
1. Physiology of the Gastrointestinal Tract. 4th Edition. Edited by Leonard R Johnson, Kim Barrett, Fayez K Ghishan, Juanita L Merchand, Hamid M Said and Jackie D. Wood; Elsevier Press; San Diego; 2006.
2. Physiology of the Gastrointestinal Tract, 5th Edition. Edited by Johnson LR, Ghishan FK, Merchand JL, Said HM and Wood JD, editors; Elsevier Press; San Diego; 2012.
PLEASE GO TO PUBMED FOR LATEST LIST OF PUBLICATIONS.
– Current funding: R37 NIH Merit Award 2009-2019; Senior Career Scientist Award (VA) 2008-2022; RO1 NIH grant, VA merit award
AGA, APS, AIN, ASCB
Reviewer for NIH and VA Study Sections; Reviewer for the Austrian Science Foundation
NIH and VA
Structural Biology and Molecular Biophysics