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Srikumar P. Chellappan, PhD

Where You Are:
Srikumar P. Chellappan, PhD

Senior Member

"We focus on regulatory pathways that promote tumor growth, angiogenesis and metastasis and how they can be targeted for drug discovery."

Office  (813) 745-6892

Education And Training
  • Postdoctoral Fellowship, Duke University Medical Center, 1991 - Molecular Biology
  • PhD, Indian Institute of Science, Bangalore, India, 1987 - Biochemistry
  • MSc, University of Kerala, India, 1981 - Zoology


The major research interest is to understand the mechanisms by which extra-cellular signals regulate the cell cycle machinery and how a loss of this regulation leads to oncogenesis. We focus on how the retinoblastoma protein and its downstream target E2F transcription factor mediate proliferation, differentiation and apoptosis in response to specific signaling cascades. In this context, we have observed that the signaling molecule Raf-1 can physically interact with the Rb protein in response to proliferative signals and inactivate it independent of cyclins and cyclin dependent kinases. Disruption of the Rb-Raf-1 interactions by a small peptide inhibits cell proliferation as well as VEGF-induced angiogenic process. Attempts are being made to identify potential drugs that can mimic this peptide. Our studies have also shown that JNK1 and p38 kinases can modulate Rb and E2F activity in opposite fashions. The potential role of these events in apoptosis is being evaluated. Our lab is also studying the role of prohibitin, a potential tumor suppressor protein that interacts with Rb and represses E2F transcriptional activity. Mutations of the prohibitin gene have been reported in breast cancer and we find that prohibitin can inhibit certain apoptotic pathways. Efforts are being made to understand the specific mechanism by which prohibitin regulates cell proliferation and apoptosis. A recent avenue of research has been on the role of nicotinic receptor signaling in lung cancer, especially how exposure to nicotine promotes the growth and progression of tumors and renders them resistant to death induced by chemotherapeutic drugs. We believe our studies will identify molecular targets for developing novel chemotherapeutic agents.

Key words: Rb, Raf-1, E2F, Cell cycle, prohibitin, nicotine, lung cancer, ASK1, p38, angiogenesis.

  • Schaal C, Chellappan SP. Nicotine-mediated cell proliferation and tumor progression in smoking-related cancers. Mol Cancer Res. 2014 Jan;12(1):14-23. Pubmedid: 24398389.
  • Trevino JG, Verma M, Singh S, Pillai S, Zhang D, Pernazza D, Sebti SM, Lawrence NJ, Centeno BA, Chellappan SP. Selective disruption of rb-raf-1 kinase interaction inhibits pancreatic adenocarcinoma growth irrespective of gemcitabine sensitivity. Mol Cancer Ther. 2013 Dec;12(12):2722-2734. Pubmedid: 24107447.
  • Sun J, He H, Pillai S, Xiong Y, Challa S, Xu L, Chellappan S, Yang S. GATA3 transcription factor abrogates Smad4 transcription factor-mediated fascin overexpression, invadopodium formation, and breast cancer cell invasion. J Biol Chem. 2013 Dec;288(52):36971-36982. Pubmedid: 24235142. Pmcid: PMC3873555.
  • Singh S, Chellappan S. Lung cancer stem cells: Molecular features and therapeutic targets. Mol Aspects Med. 2013 Sep. Pubmedid: 24016594.
  • Singh S, Bora-Singhal N, Kroeger J, Laklai H, Chellappan SP. ?Arrestin-1 and Mcl-1 modulate self-renewal growth of cancer stem-like side-population cells in non-small cell lung cancer. PLoS One. 2013 Aug;8(2):e55982. Pubmedid: 23418490. Pmcid: PMC3572139.
  • Singh S, Trevino J, Bora-Singhal N, Coppola D, Haura E, Altiok S, Chellappan SP. EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer. Mol Cancer. 2013 Mar;11:73. Pubmedid: 23009336. Pmcid: PMC3497614.
  • Perumal D, Singh S, Yoder SJ, Bloom GC, Chellappan SP. A novel five gene signature derived from stem-like side population cells predicts overall and recurrence-free survival in NSCLC. PLoS One. 2013 Feb;7(8):e43589. Pubmedid: 22952714. Pmcid: PMC3430700.
  • Pillai S, Szekeres K, Lawrence NJ, Chellappan SP, Blanck G. Regulation of interlocking gene regulatory network subcircuits by a small molecule inhibitor of retinoblastoma protein (RB) phosphorylation: cancer cell expression of HLA-DR. Gene. 2013 Jan;512(2):403-407. Pubmedid: 23041127.
  • Guo J, Kim D, Gao J, Kurtyka C, Chen H, Yu C, Wu D, Mittal A, Beg AA, Chellappan SP, Haura EB, Cheng JQ. IKBKE is induced by STAT3 and tobacco carcinogen and determines chemosensitivity in non-small cell lung cancer. Oncogene. 2013 Jan;32(2):151-159. Pubmedid: 22330135.
  • Kunigal S, Ponnusamy MP, Momi N, Batra SK, Chellappan SP. Nicotine, IFN-? and retinoic acid mediated induction of MUC4 in pancreatic cancer requires E2F1 and STAT-1 transcription factors and utilize different signaling cascades. Mol Cancer. 2012 Dec;11:24. Pubmedid: 22537161. Pmcid: PMC3464875.
  • Trevino JG, Pillai S, Kunigal S, Singh S, Fulp WJ, Centeno BA, Chellappan SP. Nicotine induces inhibitor of differentiation-1 in a Src-dependent pathway promoting metastasis and chemoresistance in pancreatic adenocarcinoma. Neoplasia. 2012 Dec;14(12):1102-1114. Pubmedid: 23308043. Pmcid: PMC3540937.
  • Pillai S, Chellappan S. ?7 nicotinic acetylcholine receptor subunit in angiogenesis and epithelial to mesenchymal transition. Curr Drug Targets. 2012 May;13(5):671-679. Pubmedid: 22300034.
  • Rastogi S, Rizwani W, Joshi B, Kunigal S, Chellappan SP. TNF-? response of vascular endothelial and vascular smooth muscle cells involve differential utilization of ASK1 kinase and p73. Cell Death Differ. 2012 Feb;19(2):274-283. Pubmedid: 21738216. Pmcid: PMC3191254.
  • Alamanda V, Singh S, Lawrence NJ, Chellappan SP. Nicotine-mediated induction of E-selectin in aortic endothelial cells requires Src kinase and E2F1 transcriptional activity. Biochem Biophys Res Commun. 2012 Feb;418(1):56-61. Pubmedid: 22240023. Pmcid: PMC3273677.
  • Davis R, Pillai S, Lawrence N, Sebti S, Chellappan SP. TNF-?-mediated proliferation of vascular smooth muscle cells involves Raf-1-mediated inactivation of Rb and transcription of E2F1-regulated genes. Cell Cycle. 2012 Jan;11(1):109-118. Pubmedid: 22185776. Pmcid: PMC3272234.
  • Johnson JL, Pillai S, Pernazza D, Sebti SM, Lawrence NJ, Chellappan SP. Regulation of matrix metalloproteinase genes by E2F transcription factors: Rb-Raf-1 interaction as a novel target for metastatic disease. Cancer Res. 2012 Jan;72(2):516-526. Pubmedid: 22086850. Pmcid: PMC3261351.
  • Johnson JL, Pillai S, Chellappan SP. Genetic and biochemical alterations in non-small cell lung cancer. Biochem Res Int. 2012;2012:940405. Pubmedid: 22928112. Pmcid: PMC3426175.
  • Chellappan SP. The Jab1-E2F1 interaction: A matter of life and death. Cell Cycle. 2011 Dec;10(23):3999-3998. Pubmedid: 22134136.
  • Pillai S, Rizwani W, Li X, Rawal B, Nair S, Schell MJ, Bepler G, Haura E, Coppola D, Chellappan S. ID1 facilitates the growth and metastasis of non-small cell lung cancer in response to nicotinic acetylcholine receptor and epidermal growth factor receptor signaling. Mol Cell Biol. 2011 Oct;31(14):3052-3067. Pubmedid: 21606196. Pmcid: PMC3133413.
  • Singh S, Pillai S, Chellappan S. Nicotinic acetylcholine receptor signaling in tumor growth and metastasis. J Oncol. 2011 May;2011:456743. Pubmedid: 21541211. Pmcid: PMC3085312.
  • Singh S, Johnson J, Chellappan S. Small molecule regulators of Rb-E2F pathway as modulators of transcription. Biochim Biophys Acta. 2011 Feb;1799(10-12):788-794. Pubmedid: 20637913. Pmcid: PMC2997897.
  • Dasgupta P, Rizwani W, Pillai S, Davis R, Banerjee S, Hug K, Lloyd M, Coppola D, Haura E, Chellappan SP. ARRB1-mediated regulation of E2F target genes in nicotine-induced growth of lung tumors. J Natl Cancer Inst. 2011 Feb;103(4):317-333. Pubmedid: 21212384. Pmcid: PMC3039728.
  • Singh S, Davis R, Alamanda V, Pireddu R, Pernazza D, Sebti S, Lawrence N, Chellappan S. Rb-Raf-1 interaction disruptor RRD-251 induces apoptosis in metastatic melanoma cells and synergizes with dacarbazine. Mol Cancer Ther. 2010 Dec;9(12):3330-3341. Pubmedid: 21139044. Pmcid: PMC3058238.
  • Pillai S, Kovacs M, Chellappan S. Regulation of vascular endothelial growth factor receptors by Rb and E2F1: role of acetylation. Cancer Res. 2010 Jun;70(12):4931-4940. Pubmedid: 20516113. Pmcid: PMC2891185.
  • Davis R, Rizwani W, Banerjee S, Kovacs M, Haura E, Coppola D, Chellappan S. Nicotine promotes tumor growth and metastasis in mouse models of lung cancer. PLoS One. 2010 Mar;4(10):e7524. Pubmedid: 19841737. Pmcid: PMC2759510.
  • Ma Y, Chen L, Wright GM, Pillai SR, Chellappan SP, Cress WD. CDKN1C negatively regulates RNA polymerase II C-terminal domain phosphorylation in an E2F1-dependent manner. J Biol Chem. 2010 Mar;285(13):9813-9822. Pubmedid: 20106982. Pmcid: PMC2843230.
  • Rizwani W, Alexandrow M, Chellappan S. Prohibitin physically interacts with MCM proteins and inhibits mammalian DNA replication. Cell Cycle. 2009 May;8(10):1621-1629. Pubmedid: 19377303. Pmcid: PMC2805263.
  • Dasgupta P, Rizwani W, Pillai S, Kinkade R, Kovacs M, Rastogi S, Banerjee S, Carless M, Kim E, Coppola D, Haura E, Chellappan S. Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines. Int J Cancer. 2009 Jan;124(1):36-45. Pubmedid: 18844224. Pmcid: PMC2826200.
  • Pillai S, Chellappan SP. ChIP on chip assays: genome-wide analysis of transcription factor binding and histone modifications. Methods Mol Biol. 2009;523:341-366. Pubmedid: 19381927.
  • Pillai S, Dasgupta P, Chellappan SP. Chromatin immunoprecipitation assays: analyzing transcription factor binding and histone modifications in vivo. Methods Mol Biol. 2009;523:323-339. Pubmedid: 19381928.
  • Rizwani W, Chellappan SP. In vitro replication assay with mammalian cell extracts. Methods Mol Biol. 2009;523:203-216. Pubmedid: 19381937.
  • Davis RK, Chellappan S. Disrupting the Rb-Raf-1 interaction: a potential therapeutic target for cancer. Drug News Perspect. 2008 July;21(6):331-335. Pubmedid: 18836591. Pmcid: PMC2800199.
  • Kinkade R, Dasgupta P, Carie A, Pernazza D, Carless M, Pillai S, Lawrence N, Sebti SM, Chellappan S. A small molecule disruptor of Rb/Raf-1 interaction inhibits cell proliferation, angiogenesis, and growth of human tumor xenografts in nude mice. Cancer Res. 2008 May;68(10):3810-3818. Pubmedid: 18483265. Pmcid: PMC3233839.
  • Rastogi S, Banerjee S, Chellappan S, Simon G. Glut-1 antibodies induce growth arrest and apoptosis in human cancer cell lines. Cancer Lett. 2007 Nov;257(2):244-251. Pubmedid: 17910902.
  • Delarue F, Adnane J, Joshi B, Blaskovich M, Wang D, Hawker J, BizouarnF, Ohkanda J, Zhu K, Hamilton A, Chellappan S, Sebti S. Farnesyltransferase and geranylgeranyltransferase I inhibitors upregulate RhoB expression by HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter. Oncogene. 2007 Feb;26(5):633-640. Pubmedid: 16909123.
  • Joshi B, Rastogi S, Morris M, Carastro L, DeCook C, Seto E, Chellappan S. Differential regulation of human YY1 and caspase 7 promoters by prohibitin through E2F1 and p53 binding sites. Biochem J. 2007 Jan;401(1):155-166. Pubmedid: 16918502.
  • Dasgupta P, Padmanabhan J, Chellappan S. Rb function in the apoptosis and senescence of non-neuronal and neuronal cells:role in oncogenesis. Curr Mol Med. 2006 Nov;6(7):719-729. Pubmedid: 17100598.
  • Dasgupta P, Chellappan S. Nicotine-mediated cell proliferation and angiogenesis: new twists to an old story. Cell Cycle. 2006 Oct;5(20):2324-2328. Pubmedid: 17102610.
  • Dasgupta P, Rastogi S, Pillai S, Ordonez-Ercan D, Morris M, Haura E, Chellappan S. Nicotine induces cell proliferation by beta-arrestin-mediated activation of Srcand Rb-Raf-1 pathways. J Clin Invest. 2006 Aug;116(8):2208-2217. Pubmedid: 16862215.
  • Peng X, Mehta R, Wang S, Chellappan S, Mehta RG. Prohibitin is a novel target gene of vitamin D involved in its antiproliferative action in breast cancer cells. Cancer Res. 2006 Jul;66(14):7361-7369. Pubmedid: 16849588.
  • Rastogi S, Joshi B, Dasgupta P, Morris M, Wright K, Chellappan S. Prohibitin facilitates cellular senescence by recruiting specific corepressors to inhibit E2F target genes. Mol Cell Biol. 2006 Jun;26(11):4161-4171. Pubmedid: 16705168. Pmcid: PMC1489107.
  • Dasgupta P, Kinkade R, Joshi B, Decook C, Haura E, Chellappan S. Nicotine inhibits apoptosis induced by chemotherapeutic drugs by up-regulating XIAP and survivin. Proc Natl Acad Sci U S A. 2006 Apr;103(16):6332-6337. Pubmedid: 16601104. Pmcid: PMC1458878.
  • Rastogi S, Joshi B, Fusaro G, Chellappan S. Camptothecin induces nuclear export of prohibitin preferentially in transformed cells through a CRM-1-dependent mechanism. J Biol Chem. 2006 Feb;281(5):2951-2959. Pubmedid: 16319068.
  • Niesen MI, Osborne AR, Yang H, Rastogi S, Chellappan S, Cheng JQ, Boss JM, Blanck G. Activation of a methylated promoter mediated by a sequence-specific DNA-binding protein, RFX. J Biol Chem. 2005 Nov;280(47):38914-38922. Pubmedid: 16166088.
  • Liu DX, Nath N, Chellappan SP, Greene LA. Regulation of neuron survival and death by p130 and associated chromatin modifiers. Genes Dev. 2005 Mar;19(6):719-732. Pubmedid: 15769944.
  • Joshi B, Ordonez-Ercan D, Dasgupta P, Chellappan S. Induction of human metallothionein 1G promoter by VEGF and heavy metals: differential involvement of E2F and metal transcription factors. Oncogene. 2005 Mar;24(13):2204-2217. Pubmedid: 15735762.
  • Dasgupta P, Sun J, Wang S, Fusaro G, Betts V, Padmanabhan J, Sebti SM, Chellappan SP. Disruption of the Rb--Raf-1 interaction inhibits tumor growth and angiogenesis. Mol Cell Biol. 2004 Nov;24(21):9527-9541. Pubmedid: 15485920. Pmcid: PMC522224.
  • Dasgupta P, Betts V, Rastogi S, Joshi B, Morris M, Brennan B, Ordonez-Ercan D, Chellappan S. Direct binding of apoptosis signal-regulating kinase 1 to retinoblastoma protein: novel links between apoptotic signaling and cell cycle machinery. J Biol Chem. 2004 Sep;279(37):38762-38769. Pubmedid: 15210709.
  • Haura EB, Cress WD, Chellappan S, Zheng Z, Bepler G. Antiapoptotic signaling pathways in non-small-cell lung cancer: biology and therapeutic strategies. Clin Lung Cancer. 2004 Sep;6(2):113-122. Pubmedid: 15476597.
  • Fusaro G, Dasgupta P, Rastogi S, Joshi B, Chellappan S. Prohibitin induces the transcriptional activity of p53 and is exported from the nucleus upon apoptotic signaling. J Biol Chem. 2003 Nov;278(48):47853-47861. Pubmedid: 14500729.
  • Nath N, Wang S, Betts V, Knudsen E, Chellappan S. Apoptotic and mitogenic stimuli inactivate Rb by differential utilization of p38 and cyclin-dependent kinases. Oncogene. 2003 Sep;22(38):5986-5994. Pubmedid: 12955077.
  • Joshi B, Ko D, Ordonez-Ercan D, Chellappan S. A putative coiled-coil domain of prohibitin is sufficient to repress E2F1-mediated transcription and induce apoptosis. Biochem Biophys Res Commun. 2003;312(2):459-466. Pubmedid: 14637159.
  • Wang S, Fusaro G, Padmanabhan J, Chellappan SP. Prohibitin co-localizes with Rb in the nucleus and recruits N-CoR and HDAC1 for transcriptional repression. Oncogene. 2002 Dec;21(55):8388-8396. Pubmedid: 12466959.
  • Fusaro G, Wang S, Chellappan S. Differential regulation of Rb family proteins and prohibitin during camptothecin-induced apoptosis. Oncogene. 2002 Jul;21(29):4539-4548. Pubmedid: 12085232.
  • Rosato RR, Almenara JA, Cartee L, Betts V, Chellappan SP, Grant S. The cyclin-dependent kinase inhibitor flavopiridol disrupts sodium butyrate-induced p21WAF1/CIP1 expression and maturation while reciprocally potentiating apoptosis in human leukemia cells. Mol Cancer Ther. 2002 Feb;1(4):253-266. Pubmedid: 12467221.
  • Chellappan SP. HOG on the promoter: regulation of the osmotic stress response. Sci STKE. 2001 Jul;2001(93):pe1-pe1. Pubmedid: 11752666.
  • Gewirtz D, Di Y, Randolph J, Jain P, Valerie K, Bullock S, Nath N, Chellappan S. Rb dephosphorylation and suppression of E2F activity in human breast tumor cells exposed to a pharmacological concentration of estradiol. Arch Biochem Biophys. 2001 Apr;388(2):243-252. Pubmedid: 11368161.
  • Cartee L, Wang Z, Decker RH, Chellappan SP, Fusaro G, Hirsch KG, Sankala HM, Dent P, Grant S. The cyclin-dependent kinase inhibitor (CDKI) flavopiridol disrupts phorbol 12-myristate 13-acetate-induced differentiation and CDKI expression while enhancing apoptosis in human myeloid leukemia cells. Cancer Res. 2001 Mar;61(6):2583-2591. Pubmedid: 11289135.
  • Nath N, Bian H, Reed EF, Chellappan SP. HLA class I-mediated induction of cell proliferation involves cyclin E-mediated inactivation of Rb function and induction of E2F activity. J Immunol. 1999 May;162(9):5351-5358. Pubmedid: 10228011.
  • Wang S, Ghosh RN, Chellappan SP. Raf-1 physically interacts with Rb and regulates its function: a link between mitogenic signaling and cell cycle regulation. Mol Cell Biol. 1998 Dec;18(12):7487-7498. Pubmedid: 9819434. Pmcid: PMC109329.
  • Vrana JA, Saunders AM, Chellappan SP, Grant S. Divergent effects of bryostatin 1 and phorbol myristate acetate on cell cycle arrest and maturation in human myelomonocytic leukemia cells (U937). Differentiation. 1998 May;63(1):33-42. Pubmedid: 9615391.
  • Freemerman AJ, Vrana JA, Tombes RM, Jiang H, Chellappan SP, Fisher PB, Grant S. Effects of antisense p21 (WAF1/CIP1/MDA6) expression on the induction of differentiation and drug-mediated apoptosis in human myeloid leukemia cells (HL-60). Leukemia. 1997 Apr;11(4):504-513. Pubmedid: 9096690.
  • Schwarz JK, Devoto SH, Smith EJ, Chellappan SP, Jakoi L, Nevins JR. Interactions of the p107 and Rb proteins with E2F during the cell proliferation response. Embo J. 1993 Mar;12(3):1013-1020. Pubmedid: 8458319. Pmcid: PMC413302.
  • Chellappan SP, Nevins JR. DNA octamer element can confer E1A trans-activation, and adenovirus infection results in a stimulation of the DNA-binding activity of OTF-1/NFIII factor. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5878-5882. Pubmedid: 2143023. Pmcid: PMC54432.
  • Dasgupta P, Chellappan S. Chromatin immunoprecipitation assays: molecular analysis of chromatinmodification and gene regulation. Methods Mol Biol. 2007 383;383:135-152. Pubmedid: 18217683.
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