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Sendurai A. Mani, Ph.D.

Present Title & Affiliation

Primary Appointment

Associate Professor, Department of Translational Molecular Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Co-Director, Metastasis Research Center, MDACC, Houston, TX
Co-Director, Center for Stem Cells & Developmental Biology, MDACC, Houston, TX

Dual/Joint/Adjunct Appointment

Member of the Graduate Faculty, The University of Texas Graduate School of Biomedical Sciences, Houston, TX

Bio Statement

Research Interests

Greater than 80% ofall cancer cases are carcinomas, formed by the transformation of epithelialcells. Metastasis remains the ultimate cause of death for the majority of thesecarcinoma patients. The molecular mechanisms by which carcinoma cells acquiremetastatic ability remains poorly understood. Carcinoma cells, which areinitially confined to the primary tumor site by the continued expression ofcell-cell adhesion molecules, acquire metastatic properties by activating alatent embryonic program, known as epithelial-mesenchymal transition (EMT).Through EMT, cancer cell acquires mesenchymal morphology, increased migrationand invasion. Most importantly, during metastasis, cancer cells recreate tumorhistopatholically similar to their tissue of origin at the metastatic sitesuggesting that the cancer cells could acquire stem cell properties beforedeparting the primary site, so that they could recreate tumor similar to theprimary site. Indeed, we and others found that cancer cells acquire stem cellproperties via EMT in addition to migratory and invasive capacities. Atpresent, our laboratory is involved in understanding the biology metastasis atthe molecular level and developing ways to diagnose and treat metastasis. 


Lab Members:
RamaSoundararajan (Assistant Professor)
NathalieSphyris
(Instructor)
Joseph Taube(Postdoc)
Steven Werden(Postdoc)

TapasreeRoysarkar (Postdoc)

AnuragParanjape (Postdoc)
MikaPietila (Postdoc)
Robiya Joseph(Postdoc)
Geraldine VidyaRaja (Graduate student)
EsmeraldaRamirez-Peña  (Graduate student)

NeerajaBhangre (Lab manager)

Administrative Assistant
Ms. Barbara Sadeghi

(713) 834-6030

bsadeghi@mdanderson.org

 


Office Address

The University of Texas MD Anderson Cancer Center
2130 West Holcombe Boulevard
Unit Number: 2951
Houston, TX 77030
Room Number: LSP9.2001
Phone: 713-792-9638
Fax: 713-834-6083
Email: smani@mdanderson.org

Education & Training

Degree-Granting Education

2000 Indian Institute of Science, Bangalore, India, PHD, Molecular Biology

Postgraduate Training

1/1998-11/2007 Postdoc, Cancer Biology, Whitehead Institute/MIT, Cambridge, MA, Dr. Robert Weinberg

Experience/Service

Academic Appointments

Member, Keck Center for Interdisciplinary Bioscience Training Programs and GCC Research Consortia, Houston, TX, 2009-present

Administrative Appointments/Responsibilities

Co-Director, CCSG-Metastasis Research Program, MDACC, Houston, TX, 1/2012-present

Honors and Awards

2012-2015 The American Cancer Society M. Patricia Alexander Research Scholar, American Cancer Society
2012-2014 Career Development Award, MDACC Prostate Cancer SPORE
2008-2013 Fellow, M. D. Anderson Research Trust, The University of TX, M. D. Anderson Cancer Center
2008-2010 V-Scholar, The Jimmy V Foundation for Cancer Research
2008-2009 MD Anderson Faculty Development Award - CCSG, The University of TX, M. D. Anderson Cancer Center
2001-2004 Postdoctoral Fellowship, Breast Cancer Reserach Program, Department of Defense

Selected Publications

Peer-Reviewed Original Research Articles

1. Liu Y, Zhou R, Baumbusch LO, Tsavachidis S, Brewster AM, Do KA, Sahin A, Hortobagyi GN, Taube JH, Mani SA, Aarøe J, Wärnberg F, Børresen-Dale AL, Mills GB, Thompson PA, Bondy ML. Genomic copy number imbalances associated with bone and non-bone metastasis of early-stage breast cancer. Breast Cancer Res Treat. e-Pub 12/4/2013. PMID: 24305980.
2. Malouf GG, Taube JH, Lu Y, Roysarkar T, Panjarian S, Estecio MR, Jelinek J, Yamazaki J, Raynal NJ, Long H, Tahara T, Tinnirello A, Ramachandran P, Zhang XY, Liang S, Mani SA, Issa JP. Architecture of epigenetic reprogramming following Twist1 mediated epithelial-mesenchymal transition. Genome Biol 14(12). e-Pub 12/2013. PMID: 24367927.
3. Taube JH, Malouf GG, Lu E, Sphyris N, Vijay V, Ramachandran PP, Ueno KR, Gaur S, Nicoloso MS, Rossi S, Herschkowitz JI, Rosen JM, Issa JP, Calin GA, Chang JT, Mani SA. Epigenetic silencing of microRNA-203 is required for EMT and cancer stem cell properties. Sci Rep 3:2687, 9/2013. PMCID: PMC3776231.
4. Romero-Aburto R, Narayanan TN, Nagaoka Y, Hasumura T, Mitcham TM, Fukuda T, Cox PJ, Bouchard RR, Maekawa T, Kumar DS, Torti SV, Mani SA, Ajayan PM. Fluorinated Graphene Oxide; a New Multimodal Material for Biological Applications. Adv Mater. e-Pub 8/2013. PMID: 24038195.
5. Ling H, Spizzo R, Atlasi Y, Nicoloso M, Shimizu M, Redis R, Nishida N, Gafà R, Song J, Guo Z, Ivan C, Barbarotto E, De Vries I, Zhang X, Ferracin M, Churchman M, van Galen J, Beverloo B, Shariati M, Haderk F, Estecio MR, Garcia-Manero G, Patijn G, Gotley D, Bhardwaj V, Imad S, Sen S, Multani A, Welsh J, Yamamoto K, Taniguchi I, Song MA, Gallinger S, Casey G, Thibodeau S, Marchand LL, Tiirikainen M, Mani S, Zhang W, Davuluri R, Mimori K, Mori M, Sieuwerts A, Martens J, Tomlinson I, Neagoe I, Negrini M, Foekens J, Hamilton S, Lanza G, Kopetz S, Fodde R, Calin G. CCAT2, a novel non-coding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. Genome Res. e-Pub 6/2013. PMID: 23796952.
6. Hollier BG, Tinnirello AA, Werden SJ, Evans KW, Taube JH, Sarkar TR, Sphyris N, Shariati M, Kumar SV, Battula VL, Herschkowitz JI, Guerra R, Chang JT, Miura N, Rosen JM, Mani SA. FOXC2 expression links epithelial-mesenchymal transition and stem cell properties in breast cancer. Cancer Res 73(6):1981-92, 3/15/2013. e-Pub 2/1/2013. PMCID: PMC3602160.
7. Lu J, Ye X, Fan F, Xia L, Bhattacharya R, Bellister S, Tozzi F, Sceusi E, Zhou Y, Tachibana I, Maru DM, Hawke DH, Rak J, Mani SA, Zweidler-McKay P, Ellis LM. Endothelial Cells Promote the Colorectal Cancer Stem Cell Phenotype through a Soluble Form of Jagged-1. Cancer Cell 23(2):171-85, 2/11/2013. e-Pub 1/31/2013. PMCID: PMC3574187.
8. Yao Y, Suraokar M, Darnay BG, Hollier BG, Shaiken TE, Asano T, Chen CH, Chang BH, Lu Y, Mills GB, Sarbassov D, Mani SA, Abbruzzese JL, Reddy SA. BSTA Promotes mTORC2-Mediated Phosphorylation of Akt1 to Suppress Expression of FoxC2 and Stimulate Adipocyte Differentiation. Sci Signal 6(257):ra2, 2013. e-Pub 1/8/2013. PMID: 23300339.
9. Zarkoob H, Taube JH, Singh SK, Mani SA, Kohandel M. Investigating the Link between Molecular Subtypes of Glioblastoma, Epithelial-Mesenchymal Transition, and CD133 Cell Surface Protein. PLoS One 8(5):e64169, 2013. e-Pub 5/2013. PMCID: PMC3667082.
10. Giordano A, Gao H, Anfossi S, Cohen E, Mego M, Lee BN, Tin S, De Laurentiis M, Parker CA, Alvarez RH, Valero V, Ueno NT, De Placido S, Mani SA, Esteva FJ, Cristofanilli M, Reuben JM. Epithelial-Mesenchymal Transition and Stem Cell Markers in Patients with HER2-Positive Metastatic Breast Cancer. Mol Cancer Ther. e-Pub 9/2012. PMID: 22973057.
11. Fan F, Samuel S, Evans KW, Lu J, Xia L, Zhou Y, Sceusi E, Tozzi F, Ye XC, Mani SA, Ellis LM. Overexpression of Snail induces epithelial-mesenchymal transition and a cancer stem cell-like phenotype in human colorectal cancer cells. Cancer Med 1(1):5-16, 8/2012. e-Pub 6/8/2012. PMCID: PMC3544430.
12. Narayanan TN, Gupta BK, Vithayathil SA, Aburto RR, Mani SA, Taha-Tijerina J, Xie B, Kaipparettu BA, Torti SV, Ajayan PM. Hybrid 2D Nanomaterials as Dual-Mode Contrast Agents in Cellular Imaging. Adv Mater. e-Pub 5/10/2012. PMID: 22573478.
13. Battula VL, Shi Y, Evans KW, Wang RY, Spaeth EL, Jacamo RO, Guerra R, Sahin AA, Marini FC, Hortobagyi G, Mani SA, Andreeff M. Ganglioside GD2 identifies breast cancer stem cells and promotes tumorigenesis. J Clin Invest. e-Pub 5/2012. PMID: 22585577.
14. Roman-Perez E, Casbas-Hernandez P, Rein J, Carey LA, Lubet RA, Mani SA, Amos KD, Troester MA, Pirone JR. Gene expression in extratumoral microenvironment predicts clinical outcome in breast cancer patients. Breast Cancer Res 14(2). e-Pub 3/19/2012. PMID: 22429463.
15. Guo W, Keckesova Z, Donaher JL, Shibue T, Tischler V, Reinhardt F, Itzkovitz S, Noske A, Zürrer-Härdi U, Bell G, Tam WL, Mani SA, van Oudenaarden A, Weinberg RA. Slug and sox9 cooperatively determine the mammary stem cell state. Cell 148(5):1015-28, 3/2/2012. PMID: 22385965.
16. Smitha S., Haseena V.S., Narayanan T.N., Reena Mary A.P., Ajayan P.M., Puthumana J., Aziz A.A., Aburto R.R., Mani S.A., Joy P.A., and Anantharaman M.R. Fluorescent Superparamagnetic Iron Oxide Core–Shell Nanoprobes for Multimodal Cellular Imaging. Mater. Express 2(4), 2012.
17. Walia V, Yu Y, Cao D, Sun M, McLean JR, Hollier BG, Cheng J, Mani SA, Rao K, Premkumar L, Elble RC. Loss of breast epithelial marker hCLCA2 promotes epithelial-to-mesenchymal transition and indicates higher risk of metastasis. Oncogene. e-Pub 9/2011. PMID: 21909135.
18. Tong Z, Chakraborty S, Sung B, Koolwal P, Kaur S, Aggarwal BB, Mani SA, Bresalier RS, Batra SK, Guha S. Epidermal growth factor down-regulates the expression of neutrophil gelatinase-associated lipocalin (NGAL) through E-cadherin in pancreatic cancer cells. Cancer 117(11):2408-18, 6/1/2011. e-Pub 12/29/2010. PMCID: PMC3134548.
19. Mego M, Mani SA, Lee BN, Li C, Evans KW, Cohen EN, Gao H, Jackson SA, Giordano A, Hortobagyi GN, Cristofanilli M, Lucci A, Reuben JM. Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer: The effect of neoadjuvant therapy. Int J Cancer. e-Pub 3/2011. PMID: 21387303.
20. Tong Z, Chakraborty S, Sung B, Koolwal P, Kaur S, Aggarwal BB, Mani SA, Bresalier RS, Batra SK, Guha S. Epidermal growth factor down-regulates the expression of neutrophil gelatinase-associated lipocalin (NGAL) through E-cadherin in pancreatic cancer cells. Cancer. e-Pub 12/29/2010. PMID: 21192057.
21. Taube JH, Herschkowitz JI, Komurov K, Zhou AY, Gupta S, Yang J, Hartwell K, Onder TT, Gupta PB, Evans KW, Hollier BG, Ram PT, Lander ES, Rosen JM, Weinberg RA, Mani SA. Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proc Natl Acad Sci U S A 107(35):15449-54, 8/2010. e-Pub 8/2010. PMCID: PMC2932589.
22. Battula VL, Evans KW, Hollier BG, Shi Y, Marini FC, Ayyanan A, Wang RY, Brisken C, Guerra R, Andreeff M, Mani SA. Epithelial-Mesenchymal Transition-Derived Cells Exhibit Multi-Lineage Differentiation Potential Similar to Mesenchymal Stem Cells. Stem Cells 28(8):1435-45, 8/2010. e-Pub 6/22/2010. PMID: 20572012.
23. Bloushtain-Qimron N, Yao J, Snyder EL, Shipitsin M, Campbell LL, Mani SA, Hu M, Chen H, Ustyansky V, Antosiewicz JE, Argani P, Halushka MK, Thomson JA, Pharoah P, Porgador A, Sukumar S, Parsons R, Richardson AL, Stampfer MR, Gelman RS, Nikolskaya T, Nikolsky Y, Polyak K. Cell type-specific DNA methylation patterns in the human breast. Proc Natl Acad Sci U S A 105(37):14076-81, 9/16/2008. PMID: 18780791.
24. Onder TT, Gupta PB, Mani SA, Yang J, Lander ES, Weinberg RA. Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res 68(10):3645-54, 5/15/2008. PMID: 18483246.
25. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4):704-15, 5/2008. PMCID: PMC2728032.
26. Liao MJ, Zhang CC, Zhou B, Zimonjic DB, Mani SA, Kaba M, Gifford A, Reinhardt F, Popescu NC, Guo W, Eaton EN, Lodish HF, Weinberg RA. Enrichment of a population of mammary gland cells that form mammospheres and have in vivo repopulating activity. Cancer Res 67(17):8131-8, 9/1/2007. PMID: 17804725.
27. Mani SA, Yang J, Brooks M, Schwaninger G, Zhou A, Miura N, Kutok JL, Hartwell K, Richardson AL, Weinberg RA. Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc Natl Acad Sci U S A 104(24):10069-74, 6/2007. PMCID: PMC1891217.
28. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA. Twist, a Master Regulator of Morphogenesis, Plays an Essential Role in Tumor Metastasis. Cell 117(7):927–939, 6/2004. PMID: 15210113.
29. Samudre KR, Mani SA, Vathsala PG, Rangarajan PN, Padmanaban G. Phenobarbitone-mediated translocation of the cytosolic proteins interacting with the 5'-proximal region of rat liver CYP2B1/B2 gene into the nucleus. Biochem Biophys Res Commun 292(2):312-7, 2002. PMID: 11906163.
30. Harish S, Khanam T, Mani S, Rangarajan P. Transcriptional activation by hepatocyte nuclear factor-4 in a cell-free system derived from rat liver nuclei. Nucleic Acids Res 29(5):1047-53, 3/1/2001. PMCID: PMC29722.
31. Mani SA, Harish S, Vathsala PG, Rangarajan PN, Padmanaban G. Receptor-mediated gene delivery approach demonstrates the role of 5'-proximal DNA region in conferring phenobarbitone responsiveness to CYP2B2 gene in rat liver in vivo. Biochem Biophys Res Commun 268(3):734-9, 2/24/2000. PMID: 10679274.
32. Fernandez MA, Mani SA, Rangarajan PN, Seshagiri PB. Sperm-mediated gene transfer into oocytes of the golden hamster: assessment of sperm function. Indian J Exp Biol 37(11):1085-92, 11/1999. PMID: 10783740.
33. Prabhu L, Upadhya P, Ram N, Nirodi CS, Sultana S, Vatsala PG, Mani SA, Rangarajan PN, Surolia A, Padmanaban G. A model for the transcriptional regulation of the CYP2B1/B2 gene in rat liver. Proc Natl Acad Sci U S A 92(21):9628-963, 1995. PMID: 7568186.

Invited Articles

1. Chang JT, Mani SA. Sheep, wolf, or werewolf: Cancer stem cells and the epithelial-to-mesenchymal transition. Cancer Lett. e-Pub 3/2013. PMID: 23499890.
2. Kolonin MG, Evans KW, Mani SA, Gomer RH. Alternative origins of stroma in normal organs and disease. Stem Cell Res. e-Pub 12/2011. PMID: 22209011.
3. May CD, Sphyris N, Evans KW, Werden SJ, Guo W, Mani SA. Epithelial-mesenchymal transition and cancer stem cells: a dangerously dynamic duo in breast cancer progression. Breast Cancer Res 13(1). e-Pub 2/2011. PMID: 21392411.
4. Mego M, Mani SA, Cristofanilli M. Molecular mechanisms of metastasis in breast cancer-clinical applications. Nat Rev Clin Oncol 7(12):693-701, 12/2010. e-Pub 10/19/2010. PMID: 20956980.
5. Blick T, Hugo H, Widodo E, Waltham M, Pinto C, Mani SA, Weinberg RA, Neve RM, Lenburg ME, Thompson EW. Epithelial mesenchymal transition traits in human breast cancer cell lines parallel the CD44(hi/)CD24 (lo/-) stem cell phenotype in human breast cancer. J Mammary Gland Biol Neoplasia 15(2):235-52, 6/2010. e-Pub 6/2010. PMID: 20521089.
6. Lu J, Steeg PS, Price JE, Krishnamurthy S, Mani SA, Reuben J, Cristofanilli M, Dontu G, Bidaut L, Valero V, Hortobagyi GN, Yu D. Breast Cancer Metastasis: Challenges and Opportunities. Cancer Research 69(12). e-Pub 5/2009.
7. Mani SA, Evans KW, Hollier BG, Guo W, and Weinberg RA. Generation of Stem-like Cells via EMT: A New Twist in Cancer Initiation and Progression. AACR Education Book(1):173, 4/2009.
8. Hollier BG, Evans K, Mani SA. The Epithelial-to-Mesenchymal Transition and Cancer Stem Cells: A Coalition Against Cancer Therapies. J Mammary Gland Biol Neoplasia 14(1):29-43, 3/2009. e-Pub 2/26/2009. PMID: 19242781.
9. Sphyris N, Mani, SA. The importance of the Epithelial-Mesenchymal Transition in Breast Cancer. Current Breast Cancer Reports 1:229-237, 2009.
10. Yang J, Mani SA, Weinberg RA. Exploring a new twist on tumor metastasis. Cancer Res 66(9):4549-52, 5/1/2006. PMID: 16651402.
11. Gupta, P., Mani, S.A., Yang, J., Hartwell, K., Weinberg, R.A.. The evolving portrait of cancer metastasis. Cold Spring Harb Symp Quant Biol 70:291-298, 2005. PMID: 16869765.

Editorials

1. Sphyris N, Mani SA. pIgR: Frenemy of Inflammation, EMT, and HCC Progression. J Natl Cancer Inst. e-Pub 10/2011. PMID: 22025623.
2. Mani SA, Barton MC. HDAC3 at the Fulcrum of an Epithelial-Mesenchymal Balance. Mol Cell 43(5):697-698, 9/2011. e-Pub 2011. PMID: 21884971.

Book Chapters

1. Taube, J., Mani, S.A. Epithelial-to-mesenchymal transition, stem cells, and cancer progression. In: Nova publishers book on "Stem Cell, Regenerative Medicine and Cancer". Nova, 2010.

Last updated: 5/29/2014