Einstein/Montefiore Department of Medicine

Department Faculty

Dr. Sridhar Mani, M.D.

Sridhar Mani, M.D.

Professor, Department of Medicine (Oncology)

Professor, Department of Molecular Pharmacology

Professor, Department of Genetics

Areas of Research: Role of Microbiome-Host Interactions in Physiology and Disease, Orphan Nuclear Receptors in Physiology and Disease, Gastrointestinal Cancer, Drug Discovery and Development

Professional Interests

Orphan nuclear receptors (those that lack a well defined physiologic ligand) control nearly every major physiologic and biochemical process in eukaryotes - cell metabolism (e.g., cholesterol, energy, bile acids), xenobiotic detoxification, cell differentiation (e.g., gastrulation, retinal development), circadian rhythm, and cancer cell growth and apoptosis (e.g., NURR77).  Of these receptors, the steroid and xenobiotic receptor (SXR) is a key regulator of genes encoding drug metabolizing and transport proteins.  In addition, SXR has been implicated in cancer drug resistance, carcinogenesis, innate immunity, infection control and pathophysiologic states like osteomalacia. Our laboratory focuses on defining the role of SXR and other orphans by using novel and dynamic models of human pathophysiology in (i) xenobiotic metabolism and pharmacology; (ii) carcinogenesis, organogenesis and anticancer drug resistance and (iii) innate immunity.

Recently, our laboratory has directed interests in the mammalian microbiome. We have discovered a novel link between the microbial metabolome and orphan nuclear receptor, SXR/PXR (Immunity, 2014). Further work in the laboratory is focussed on defining how the microbial environment shapes health and disease.


Lab website: https://sites.google.com/view/mani-lab

Alternative Landing Page: http://www.einstein.yu.edu/labs/sridhar-mani/




Selected Publications

Recent Publications: 

1.  Huang H, Wang H, Ganjam K, Staudinger J, Redinbo M, Mani S. (2007) Inhibiting the transcriptional control of drug metabolism. Oncogene. 26(2):258-68.

2.    Wang H, Li H, Moore LB, Maglich JM, Goodwin B, Price R, Itoop ORR, Jones SA, Wisely B, Creech K, Parks DJ, Collins JL, Willson TM, Kalpana G, Xie W, Redinbo M, Moore JT, Mani S (2007) The Phytoestrogen Coumestrol is a Naturally Occuring Antagon ist of the Pregnane X Receptor (PXR). Mol Endocrinol. 22:838-57 

3.   Ekins S*, Chang C*, Mani S*, Krasowski MD, Reschly EJ, Iyer M, Kholodovych V, Ai N, Welsh WJ, Sinz M, Swaan PW, Patel R, Bachmann K.(2007) Human pregnane X receptor antagonists and agonists define molecular requirements for different binding sites. Mol Pharmacol. 72:592-603 (*equal contribution)

4.  Gupta D, Venkatesh M, Wang H, Kim S, Sinz M, Goldberg GL, Whitnet K, Mani S.  Expanding the roles for PXR in Cancer:  Proliferation and Drug Resistance in Ovarian Cancer. (2008) Clin Cancer Res 14(17):5332-40. (F1000) 

5.    Das B, Madhukumar AV, Kim S, Sinz M, Zvyaga TA, Power EC, Ganellin CR, Mani S. (2008)  Synthesis of novel ketoconazole derivatives as antagonists of the human Pregnane X Receptor (PXR; NR1I2l also termed SXR, PAR). Bioorg Med Chem Lett. 18(14):3974-7

6.  Ekins S, Kholodovych V, Ai N, Sinz M, Gal J, Gera L, Welsh WJ, Bachmann K, Mani S. (2008) Computational discovery of novel low micromolar human pregnane x receptor antagonists. Mol Pharmacol. 74(3):662-72

7. Wallace BD, Wang H, Lane KT, Scott JE, Orans J, Koo JS, Venkatesh M, Jobin C, Yeh LA, Mani S, Redinbo MR. (2010) Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330(6005):831-5

8. Mani S, Boelsterli UA, Redinbo MR. (2014) Understanding and modulating mammalian-microbial communication for improved human health. Annu Rev Pharmacol Toxicol. 2014;54:559-80.

9.  Biswas A, Pasquel D, Tyagi RK, Mani S. (2011)Acetylation of pregnane x receptor protein determines selective function independent of ligand activation. Biochem Biophys Res Commun.  406(3):371-6

10. Wang H, Venkatesh M, Li H, Goetz R, Mukherjee S, Biswas A, Zhu L, Kaubisch A, Wang L, Pullman J, Whitney K, Kuro-o M, Roig AI, Shay JW, Mohammadi M, Mani S. (2011) Pregnane X receptor activation induces FGF19-dependent tumor aggessiveness in humans and mice. J Clin Invest. 121(8):3220-32

9.   Dou W, Mukherjee S, Li H, Venkatesh M, Wang H, Kortagere S, Peleg A, Chilimuri SS, Wang ZT, Feng Y, Fearon ER, Mani S. (2012) Alleviation of gut inflammation by Cdx2/Pxr pathway in a mouse model of chemical colitis. PLoS One 7(7):e36075

10. Li H, Redinbo MR, Venkatesh M, Ekins S, Chaudhry A, Bloch N, Negassa A, Mukherjee P, Kalpana G, Mani S. (2013)  Novel yeast-based strategy unveils antagonist binding regions on the nuclear xenobiotic receptor PXR. J Biol Chem. 288(19):13655-68

11. Dou W, Zhang J, Zhang E, Sun A, Ding L, Chou G, Wang Z, Mani S. (2013) Chrysin ameliorates chemically induced colitis in the mouse through modulation of a PXR/NF-kB signaling pathway.  J Pharmacol Exp Ther. 345(3):473-82

12. Venkatesh M, Mukherjee S, Wang H, Li H, Sun K, Benechet AP, Qiu Z, Maher L, Redinbo MR, Phillips RS, Fleet JC, Kortagere S, Mukherjee P, Fasano A, Le Ven J, Nicholson JK, Dumas ME, Khanna KM, and Mani S. (2014) Symbiotic Bacterial Metabolites Regulate Gastrointestinal Barrier Function via the Xenobiotic Receptor PXR and Toll-like Receptor 4. Immunity.  41(2):296-310

13. Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, Flament C, Rusakiewicz S, Routy B, Roberti MP, Duong CP, Poirier-Colame V, Roux A, Becharef S, Formenti S, Golden E, Cording S, Eberl G, Schlitzer A, Ginhoux F, Mani S, Yamazaki T, Jacquelot N, Enot DP, Bérard M, Nigou J, Opolon P, Eggermont A, Woerther PL, Chachaty E, Chaput N, Robert C, Mateus C, Kroemer G, Raoult D, Boneca IG, Carbonnel F, Chamaillard M, Zitvogel L (2015). Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 350(6264):1079-84.

14. Ranhotra HS, Flannigan KL, Brave M, Mukherjee S, Lukin DJ, Hirota SA, Mani S. Xenobiotic Receptor Mediated Regulation of Intestinal Barrier Function and Innate Immunity.  Nucl receptor Res.  2016;3. pii: 101199.

15. Qiu Z, Cervantes JL, Cicek BB, Mukherjee S, Venkatesh M, Maher LA, Salazar JC, Mani S, Khanna KM. Pregnane X Receptor Regulates Pathogen-Induced Inflammation and Host Defense Against an Intracellular Bacterial Infection Through Toll-like Receptor 4. Sci Rep. 2016 Aug 23;6:31936.

16. Stepankova M, Bartonkova I, Jiskrova E, Vrzal R, Mani S*, Kortagere S, Dvorak Z*. Methylindole and Methoxyindoles are Agonists and Antagonists of the Human Aryl Hycrocarbon Receptor.  Mol Pharmacol. 2018 Jun;93(6):631-644. * co-senior

17. Abbott KL, Chaudhury CS, Chandran A, Vishveshwara S, Dvorak Z, Jiskrova E, Poulikova K, Vyhlidalova B, Mani S*, Pondugula SR*. Belinostat, at its Clinically Relevant Concentrations, Inhibits Rifampicin-Induced CY3A4 and MDR1 Gene Expression. Mol Pharmacol. 2019 Mar;95(3):324-334. * co-senior


18. Dvorák Z, Kopp F, Costello CM, Kemp JS, Li H, Vrzalová A, Štepánková M, Bartonková I, Jiskrová E, Poulíková K, Vyhlídalová B, Nordstroem LU, Karunaratne CV, Ranhotra HS, Mun KS, Naren AP, Murray IA, Perdew GH, Brtko J, Toporova L, Schön A, Wallace WG, Walton WG, Redinbo MR, Sun K, Beck A, Kortagere S, Neary MC, Chandran A, Vishveshwara S, Cavalluzzi MM, Lentini G, Cui JY, Gu H, March JC, Chatterjee S, Matson A, Wright D, Flannigan KL, Hirota SA, Sartor RB, Mani S*. Targeting the Pregnane X receptor using microbial metabolite mimicry. EMBO Mol Med. 2020 Apr 7;12(4):e11621. (Cover Page)


19.De A, Chen W, Li H, Wright JR, Lamendella R, Lukin DJ, Szymczak WA, Sun K, Kelly L, Ghosh S,  Kearns DB, He Z, Jobin C, Luo X, Byju A, Chatterjee S, San Yeoh B, Vijay-Kumar M, Tang JX, Prajapati M, Bartnikas TB, Mani S*. Bacterial Swarmers Enriched During Intestinal Stress Ameliorate Damage. Gastroenterology. 2021 Mar 16:S0016-5085(21)00524-2. doi: 10.1053/j.gastro.2021.03.017.

20. Chen W, Mani N, Karani H, Li H, Mani S*, Tang JX. Confinement discerns swarmers from planktonic bacteria. Elife. 2021 Apr 22;10:e64176. doi: 10.7554/eLife.64176.




More Information About Dr. Sridhar Mani

Mani Lab


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Research Information