Bile Acids and Salts; Cholestasis; Digestive System Diseases; MicroRNAs; Gene Regulatory Networks
Over the last two decades, my research has focused on the mechanisms of regulation of bile acid transporters in liver during development and in pathological situations such as the human liver disease cholestasis. My main focus over the last decade has been on the role of Nuclear Receptors (with specific reference to FXR) on the regulation of Bile salt export pump (BSEP) a canalicular transporter for bile acids in the hepatocytes. I have recently also explored the role of microRNAs (mIRs) in regulating bile salt transporters in liver in physiology and pathophysiology. Since the beginning of this year, I am conducting research into molecular mechanisms of regulation of Inositol 3-phosphate receptors (IP3Rs) that act as Ca-channels in the endoplasmic reticulum (ER) with specific focus on the promoters of the Type 2 and 3 isoforms and their regulation by microRNAs.
Specialized terms: Gene Regulation; Bile Acid Transporters; Cholestasis; Development; Inositol Phosphate Receptors; MicroRNAs
Extensive Research Description
1. Regulatory mechanisms of Type 2 and Type 3 Inositol 3-phosphate receptors (IP3Rs) in hepatocytes and cholangiocytes respectively by isolation and characterization of their respective promoters
2. Role of microRNAs (mIRs) in regulation of Type 2 and Type 3 Inositol 3-phosphate receptors (IP3Rs)
3. Molecular Mechanisms of Bile acid/organic ion transporter regulation in hepatic physiological and pathological states including cholestasis
- Ananthanarayanan, M., Banales, J.M., Guerra, M.T., Spirli, C., Munoz-Garrido, P., Tafur, D., Saez, E., Mitchell-Richards, K.A and Nathanson, M.H. Post-translational regulation of the type III Inositol 1,4,5-trisphosphate by miRNA-506. J.Biol.Chem. In Press. Nov.5,2014
- Ghonem,N.S, Ananthanarayanan, M, Soroka, C.J, and Boyer, J.L. PPARa activates human MDR3/ABCB4 transcription and increases rat biliary phosphatidylcholine secretion. Hepatology DOI: 10.1002/hep.26894, 2013.
- Allen, R.M., Marquart, T.J., Albert, C.J., Suchy, F.J., Wang, D.Q-H., Ananthanarayanan, M., Ford, D.A., and Baldan, A. miR-33 controls the expression of biliary transporters and mediates statin- and diet-induced hepatotoxicity. EMBO Molecular Medicine, 4:1-14, 2012.
- Ananthanarayanan, M., Li, Yanfeng., Surapureddi, S., Balasubramaniyan, N., Ahn, Jaeyong, Goldstein, J.A., and Suchy. F.J. Histone H3K4 trimethylation by MLL3 as part of ASCOM complex is critical for NR activation of bile acid transporter genes and is downregulated in cholestasis. . Am. J. Physiol. (GI/Liver Physiol). In Press. 11 Feb 2011.
- Geier, A., Martin, I., Dietrich, C., Balasubramaniyan, N., Strauch, S., Suchy, F.J., Gartung, C., Trautwein, C., and Ananthanarayanan, M. Hepatocyte nuclear factor 4 alpha is a central transactivator of the Ntcp gene in rodents. Am. J. Physiol. (GI/Liver Physiol.) , 295: 226-223, 2008
- Balasubramaniyan, N., Shahid, M.., Suchy, F.J., and Ananthanarayanan, M. Multiple mechanisms of ontogenic regulation of Nuclear Receptors during rat liver development. Am. J. Physiol. (Gastroinstest. Liver Physiol.) 288: G251 -G260 , 2005.
- Ananthanarayanan, M., SiDe, L., Balasubramaniyan, N., Suchy, F.J., and Walsh, M.J. Ligand-dependent activation of the Farnesoid x receptor directs methylation of Histone H3 by CARM1. J. Biol. Chem. 279: 54348-54357, 2004
- Shih, D.Q., Bussen, M., Sehayek, E., Ananthanarayanan, M., Shneider, B.L., Suchy, F.J., Shefer, S., Bollineni, J., Gonzalez, F.J., Breslow, J.L., and Stoffel, M. Hepatocyte nuclear factor-1? is an essential regulator of bile acid and plasma cholesterol
- Ananthanarayanan, M., Balasubramanian, N., Makishima, M., Mangelsdorf, D.J., and Suchy, F.J. Human Bile Salt Export Pump (BSEP) Promoter is Transactivated by Farnesoid X Receptor/ Bale Acid Receptor (FXR/BAR) J. Biol. Chem.276: 28857-28865, 2001