Embedded Files
1. Huang H, Wang H, Ganjam K, Staudinger J, Redinbo M, Mani S. Inhibiting the transcriptional control of drug metabolism. Oncogene. 26(2):258-68 (2007)
2. Das B, Madhukumar AV, Anguiano J, Kim S, Sinz M, Zvyaga TA, Power EC, Ganellin CR, Mani S. Synthesis of novel ketoconazole derivatives as antagonists of the human Pregnane X Receptor (PXR; NR1I2l alsotermed SXR, PAR). Bioorg Med Chem Lett. 18(14):3974-7 (2008)
3. Ekins S, Ni A, Sinz M, Gal J, Gera L, Welsh WJ, Mani S. Computational discovery of novel low micromolar human pregnane x receptor antagonists. Mol Pharmacol. 74(3):662-72 (2008)
4. Das B, Madhukumar AV, Anguiano J, Mani S. Synthesis and Biological Evaluation of 2H-benzo[b][1,4] Oxazine Derivatives as Hypoxia Targeted Compounds for Cancer Therapeutics. Bioorg Med Chem Lett. 19(15):4204-6 (2009)
5. Wang H, Li H, Moore LB, Johnson MD, Maglich JM, Goodwin B, Ittoop OR, Wisely B, Creech K, Parks DJ,Collins JL, Willson TM, Kalpana GV, Venkatesh M, Xie W, Cho SY, Roboz J, Redinbo M, Moore JT, Mani S. Thephytoestrogen coumestrol is a naturally occurring antagonist of pregnane x receptor (PXR). Mol Endo. 22(4):838-57(2008)
6. Ekins S*, Chang C*, Mani S*, Krasowski MD, Reschly EJ, Iyer M, Kholodovch V, Ai Ni, Welsh WJ, Sinz M, Swaan PW, Patel R, Bachman K. Human pregnane x receptor antagonists and agonists define molecular requirements for different binding sites. Mol Pharmacol. 72(3):592-603 (2007)
7. Gupta D, Venkatesh M, Wang H, Kim S, Sinz M, Goldberg GL, Whitney K, Longley C, Mani S. Expanding the roles for PXR in Cancer: Proliferation and Drug Resistance in Ovarian Cancer, Clin Cancer Res. 14(17):5332-40(2008) (F1000)
8. Wallace BD, Wang H, Lane KT, Scott JE, Orans J, Koo JS, Venkatesh M, Jobin C, Yeh LA, Mani S, Redinbo MR. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science. 330(6005):831-5 (2010)
9. Smith NF, Mani S, Schuetz EG, Yasuda K, Sissung TM, Bates SE, Figg WD, Sparreboom A. Induction of CYP3A4 by Vinblastine: Role of the nuclear receptor NR1I2. Ann Pharmacother. 44(11):1709-17 (2010)
10. Kortagere S, Krasowski MD, Reschly EJ, Venkatesh M, Mani S, Ekins S. Evaluation of computational docking to identify pregnane X receptor agonists in the ToxCast database. Environ Health Perspect. 118(10):1412-7 (2010)
11. Krausova L, Stejskalova L, Wang H, Vrzal R, Dvorak Z, Mani S, Pavek P. Metformin suppresses pregnane X receptor (PXR)-regulated transactivation of CYP3A4 gene. Biochem Pharmacol. 82(11):1771-80 (2011)
12. 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. Pregnane X receptor activation induces FGF19- dependent tumor aggressiveness in humans and mice. J Clin Invest. 121(8):3220-32 (2011)
13. Venkatesh M, Wang H, Cayer J, Leroux M, Salvail D, Das B, Wrobel JE, Mani S. In vivo and in vitro characterization of a first-in-class novel azole analog that targets pregnane X receptor activation. Mol Pharmacol. 80(1):124-35 (2011)
14. Biswas A, Pasquel D, Tyagi RK, Mani S. Acetylation of pregnane X receptor protein determines selective function independent of ligand activation. Biochem Biophys Res Commun. 406(3):371-6 (2011)
15. Dou V, Mukherjee S, Li H, Venkatesh M, Wang H, Kortagere S, Peleg A, Chillimuri SS, Wang ZT, Feng Y, Fearon E, Mani S. Baicalein Abrogates Inflammation through cdx2/Pregnane X Receptor (pxr) Pathway in a Mouse Model of Chemical Colitis. PLoS One 7(7):e36075 (2012)
16. Li H, Redinbo MR, Venkatesh M, Ekins S, Chaudhry A, Bloch N, Negassa A, Mukherjee P, Kalpana G, Mani S. Novel yeast-based strategy unveils antagonist binding regions on the nuclear xenobiotic receptor PXR. J Biol Chem. 288(19):13655-68 (2013)
17. Dou W, Zhang J, Zhang E, Sun A, Ding L, Chou G, Wang Z, Mani S. Chrysin ameliorates chemically induced colitis in the mouse through modulation of a PXR/NF-κB signaling pathway. J Pharmacol Exp Ther. 345(3):472-82 (2013)
18. Dou W, Zhang J, Sun A, Zhang E, Ding L, Mukherjee S, Wei X, Chou G, Wang ZT, Mani S. Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signalling. Br J Nutr. Mar 110:599-608 (2013)
19. Roberts AB, Wallace BD, Venkatesh MK, Mani S, Redinbo MR. Molecular Insights into Microbial β- Glucuronidase Inhibition to Abrogate CPT-11 Toxicity. Mol Pharmacol. 84(2):208-17 (2013)
20. 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, Mani S. Symbiotic Bacterial Metabolites Regulate Gastrointestinal Barrier Function via the Xenobiotic Sensor PXR and Toll-like Receptor 4. Immunity 41(2):296-310 (2014)
21. Zhang J, Ding L, Wang B, Ren G, Sun A, Deng C, Wei X, Mani S, Wang Z, and Dou W. Notoginsenoside R1 Attenuates Experimental Inflammatory Bowel Disease via Pregnane X Receptor Activation. JPET 352(2):315-24 (2015)
22. Pondugula SR, Flannery PC, Abbott KL, Coleman ES, Mani S, Samuel T, Xie W. Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. Toxicol Lett.232(3):580-9 (2015)
23. 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. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 350(6264):1079-84 (2015)
24. Wallace BD, Roberts AB, Pollet RM, Ingle JD, Biernat KA, Pellock SJ, Venkatesh MK, Guthrie L, O'Neal SK, Robinson SJ, Dollinger M, Figueroa E, McShane SR, Cohen RD, Jin J, Frye SV, Zamboni WC, Pepe-Ranney C, Mani S, Kelly L, Redinbo MR. Structure and Inhibition of the Microbiome β-Glucuronidases Essential to the Alleviation of Cancer Drug Toxicity. Chem Biol. 22(9):1238-49 (2015)
25. Pasquel D, Doricakova A, Li H, Kortagere S, Krasowski MD, Biswas A, Walton WG, Redinbo MM, Dvorak Z, Mani S. Acetylation of lysine 109 modulates pregnane X receptor DNA binding and transcriptional activity. Biochim Biophys Acta. (GRM) Feb 9. pii: S1874-9399(16)30003-7 (2016)
26. 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. 6:31936 (2016)
Conference Report:
Liu JM, Lipton JM, Mani S. Sixth International Congress on Shwachman-Diamond syndrome: from patients to genes and back. Ann N Y Acad Sci. 1242(1):26-39 (2011)
Book Chapters:
1. Mani S, Buzaid A, Cadman E. Pharmacology of antineoplastic agents, multidrug resistance and the future. In: Hoffman R Benz EJ, Sanford JS, Furie B, Cohen HJ (eds), Hematology: Basic Principles and Practice 2nd edition, 1919 pp. New York, Churchill Livingstone, 1994.
2. Mani S. Hepatobiliary Cancer, Pancreatic Cancer, and Neuroendocrine Cancers of the GI Tract, In: E. E. Vokes, H. M. Golomb (Eds), Oncologic Therapies 2nd Edition, 500 pp Springer Verlag, NY 2002
3. Mani S, Stein C. Antisense Oligonucleotides as Cancer Therapy. Semin Oncol., Semin Oncol. 2005 Dec;32(6):563-72.
4. S, Stein C. Antisense Inhibition of Gene Expression. In Cancer: Principles of Oncology 7th Edition (DeVita et al), 2005
5. Mani S, Stein C. Antisense Oligonucleotides as Cancer Therapy: Past, Present and its Future. In: G.F. Schwartz (Ed), Combination Drug Therapies 1st Edition (Humana Press)(in press)
6. Mani S. Orphan Nuclear Receptors and Cancer, Encyclopedia on Cancer, 2nd Edition, 2007
Pubmed URL(s):
https://www.ncbi.nlm.nih.gov/pubmed/?term=Mani+and+PXR
https://www.ncbi.nlm.nih.gov/pubmed/?term=Mani+Sridhar+and+cancer
https://www.ncbi.nlm.nih.gov/pubmed/?term=Sridhar+Mani
https://www.ncbi.nlm.nih.gov/pubmed/?term=Mani+S+and+Pestell
Independent Papers (Research Reproducibility in-part or whole)
Publication: Liu J, Li H, Tian Y, Guo M, Sahin C, Kamata S, Honda A, Campbell J, Shi J, Yurtal ED, Yang D, Jachimowicz M, Hu S, Gong Y, Navarre W, Ishii I, Cummins CL, Peng H, Wang S, Wang X, Mani S, Krause HM. Microbial 10-oxostearic acid protects mice against colitis via the nuclear receptor PPARα. Nat Microbiol. 2026 Aug;11(8):2232-2246. doi: 10.1038/s41564-026-02321-7. Epub 2026 Apr 8. PMID: 41951975.
Reproducibility: Chuck J, Parsons JV, Solt LA. A microbial PPARadigm for gut protection. Nat Microbiol. 2026 Aug;11(8):2084-2085. doi: 10.1038/s41564-026-02423-2. PMID: 42533068.
Publication: 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, Mani S. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity. 2014 Aug 21;41(2):296-310. doi: 10.1016/j.immuni.2014.06.014. Epub 2014 Jul 24. PMID: 25065623; PMCID: PMC4142105.
Reproducibility: Dodd D, Spitzer MH, Van Treuren W, Merrill BD, Hryckowian AJ, Higginbottom SK, Le A, Cowan TM, Nolan GP, Fischbach MA, Sonnenburg JL. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature. 2017 Nov 30;551(7682):648-652. doi: 10.1038/nature24661. Epub 2017 Nov 22. PMID: 29168502; PMCID: PMC5850949.
Zhao Q, Chen T, Ni C, Hu Y, Nan Y, Lin W, Liu Y, Zheng F, Shi X, Lin Z, Zhu J, Lin Z. Indole-3-propionic Acid Attenuates HI-Related Blood-Brain Barrier Injury in Neonatal Rats by Modulating the PXR Signaling Pathway. ACS Chem Neurosci. 2022 Oct 5;13(19):2897-2912. doi: 10.1021/acschemneuro.2c00418. Epub 2022 Sep 21. PMID: 36129348.
Pulakazhi Venu VK, Saifeddine M, Mihara K, et al. The pregnane X receptor and its microbiota-derived ligand indole 3-propionic acid regulate endothelium-dependent vasodilation. Am J Physiol Endocrinol Metab 317: E350-E361, 2019. doi: 10.1152/ajpendo.00572.2018.
Ren T, Li D, Sun F, Pan L, Wang A, Li X, Bao Y, Zhang M, Zheng F, Yue H. Indole Propionic Acid Regulates Gut Immunity: Mechanisms of Metabolite-Driven Immunomodulation and Barrier Integrity. J Microbiol Biotechnol. 2025 Aug 18;35:e2503045. doi: 10.4014/jmb.2503.03045. PMID: 40825672; PMCID: PMC12375546. (review summarizing all prior studies published)
Lin T, Chen Y, Liu L, Wu T, Qian Y, Jin B. Recent advances in gut microbiota metabolite regulation of hepatic pregnane X receptor. Front Immunol. 2025 Nov 24;16:1692684. doi: 10.3389/fimmu.2025.1692684. PMID: 41368631; PMCID: PMC12682789. (review summarizing all prior studies published)
Wang S, Xiong L, Ruan Z, Gong X, Luo Y, Wu C, Wang Y, Shang H, Chen J. Indole-3-propionic acid alleviates sepsis-associated acute liver injury by activating pregnane X receptor. Mol Med. 2023 May 19;29(1):65. doi: 10.1186/s10020-023-00658-x. PMID: 37208586; PMCID: PMC10197241.
Flannigan KL, Nieves KM, Szczepanski HE, Serra A, Lee JW, Alston LA, Ramay H, Mani S, Hirota SA. The Pregnane X Receptor and Indole-3-Propionic Acid Shape the Intestinal Mesenchyme to Restrain Inflammation and Fibrosis. Cell Mol Gastroenterol Hepatol. 2023;15(3):765-795. doi: 10.1016/j.jcmgh.2022.10.014. Epub 2022 Oct 26. PMID: 36309199; PMCID: PMC9883297.
Xiao HW, Cui M, Li Y, Dong JL, Zhang SQ, Zhu CC, Jiang M, Zhu T, Wang B, Wang HC, Fan SJ. Gut microbiota-derived indole 3-propionic acid protects against radiation toxicity via retaining acyl-CoA-binding protein. Microbiome. 2020 May 20;8(1):69. doi: 10.1186/s40168-020-00845-6. PMID: 32434586; PMCID: PMC7241002.
Peng R, Song C, Gou S, Liu H, Kang H, Dong Y, Xu Y, Hu P, Cai K, Feng Q, Guan H, Li F. Gut Clostridium sporogenes-derived indole propionic acid suppresses osteoclast formation by activating pregnane X receptor. Pharmacol Res. 2024 Apr;202:107121. doi: 10.1016/j.phrs.2024.107121. Epub 2024 Feb 29. PMID: 38431091.
Li L, Jia M, Yang C, Zhao Y, Hu J, Zhao Y, Hu X, Ning F, Ding C, Li Q, Gong J, Jia X, Xu K, Wang Y, Zhou S, Deng L, Shi L, Chen X, Liu X, Liu Z. Gut microbial-derived indole-3-propionate improves cognitive function in Alzheimer's disease. Sci Adv. 2025 Nov 28;11(48):eadw8410. doi: 10.1126/sciadv.adw8410. Epub 2025 Nov 28. PMID: 41313780; PMCID: PMC12662223.
Serger E, Luengo-Gutierrez L, Chadwick JS, Kong G, Zhou L, Crawford G, Danzi MC, Myridakis A, Brandis A, Bello AT, Müller F, Sanchez-Vassopoulos A, De Virgiliis F, Liddell P, Dumas ME, Strid J, Mani S, Dodd D, Di Giovanni S. The gut metabolite indole-3 propionate promotes nerve regeneration and repair. Nature. 2022 Jul;607(7919):585-592. doi: 10.1038/s41586-022-04884-x. Epub 2022 Jun 22. PMID: 35732737. (our role was to simply provide the mice and advice on mouse work)
Publication: 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. Pregnane X receptor activation induces FGF19-dependent tumor aggressiveness in humans and mice. J Clin Invest. 2011 Aug;121(8):3220-32. doi: 10.1172/JCI41514. Epub 2011 Jul 11. PMID: 21747170; PMCID: PMC3148718.
Reproducibility: Planque C, Rajabi F, Grillet F, Finetti P, Bertucci F, Gironella M, Lozano JJ, Beucher B, Giraud J, Garambois V, Vincent C, Brown D, Caillo L, Kantar J, Pelegrin A, Prudhomme M, Ripoche J, Bourgaux JF, Ginestier C, Castells A, Hollande F, Pannequin J, Pascussi JM. Pregnane X-receptor promotes stem cell-mediated colon cancer relapse. Oncotarget. 2016 Aug 30;7(35):56558-56573. doi: 10.18632/oncotarget.10646. PMID: 27448961; PMCID: PMC5302934.
Robbins D, Cherian M, Wu J, Chen T. Human pregnane X receptor compromises the function of p53 and promotes malignant transformation. Cell Death Discov. 2016 Apr 18;2:16023. doi: 10.1038/cddiscovery.2016.23. PMID: 27547448; PMCID: PMC4979430.
Bansard L, Bouvet O, Moutin E, Le Gall G, Giammona A, Pothin E, Bacou M, Hassen-Khodja C, Bordignon B, Bourgaux JF, Prudhomme M, Hollande F, Pannequin J, Pascussi JM, Planque C. Niclosamide induces miR-148a to inhibit PXR and sensitize colon cancer stem cells to chemotherapy. Stem Cell Reports. 2022 Apr 12;17(4):835-848. doi: 10.1016/j.stemcr.2022.02.005. Epub 2022 Mar 10. PMID: 35276090; PMCID: PMC9023769.
Habano W, Gamo T, Terashima J, Sugai T, Otsuka K, Wakabayashi G, Ozawa S. Involvement of promoter methylation in the regulation of Pregnane X receptor in colon cancer cells. BMC Cancer. 2011 Feb 22;11:81. doi: 10.1186/1471-2407-11-81. PMID: 21342487; PMCID: PMC3053268.
Raynal C, Pascussi JM, Leguelinel G, Breuker C, Kantar J, Lallemant B, Poujol S, Bonnans C, Joubert D, Hollande F, Lumbroso S, Brouillet JP, Evrard A. Pregnane X Receptor (PXR) expression in colorectal cancer cells restricts irinotecan chemosensitivity through enhanced SN-38 glucuronidation. Mol Cancer. 2010 Mar 2;9:46. doi: 10.1186/1476-4598-9-46. PMID: 20196838; PMCID: PMC2838814.
Bansard L, Laconde G, Delfosse V, Huet T, Ayeul M, Rigal E, Donati Q, Gerbal-Chaloin S, Daujat-Chavanieu M, Brunel L, Legrand B, Chavanieu A, Martin AR, Pannequin J, Bourguet W, Amblard M, Pascussi JM. Targeting pregnane X receptor with a potent agonist-based PROTAC to delay colon cancer relapse. Oncogenesis. 2025 Aug 30;14(1):34. doi: 10.1038/s41389-025-00573-2. PMID: 40885723; PMCID: PMC12398506.
Publication: Huang H, Wang H, Sinz M, Zoeckler M, Staudinger J, Redinbo MR, Teotico DG, Locker J, Kalpana GV, Mani S*. Inhibition of drug metabolism by blocking the activation of nuclear receptors by ketoconazole. Oncogene. 2007;26(2):258-268.
Reproducibility (feasibility of allosteric antagonism): Kamaraj R, Drastik M, Maixnerova J, Pavek P. Allosteric Antagonism of the Pregnane X Receptor (PXR): Current-State-of-the-Art and Prediction of Novel Allosteric Sites. Cells. 2022 Sep 24;11(19):2974. doi: 10.3390/cells11192974. PMID: 36230936; PMCID: PMC9563780.
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