Sendurai Mani

Sendurai Mani

Research Scientist

Translational Oncology

Warren Alpert Medical School of Brown University

Location USA, Providence

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Dr. Sendurai Mani is a Dean’s Professor of Translational Oncology, Professor of Pathology and Laboratory Medicine, Associate Director for Translational Oncology at the Legorreta Cancer Center, Director of Translational Research Disease Groups, and Director of the Stem Cell Center at the Warren Alpert Medical School of Brown University. He is one of the world’s leading authorities on the epithelial-mesenchymal transition (EMT) in cancer, best known for two landmark papers — the co-discovery of FOXC2 as a key regulator of metastasis and basal-like breast cancer (PNAS, 2007), and his landmark Cell 2008 paper demonstrating that the EMT generates cells with cancer stem cell properties, one of the most highly cited and influential works in the field of cancer biology. His research program focuses on understanding the molecular mechanisms driving cancer metastasis, drug resistance, and tumor relapse, with particular emphasis on EMT, cancer stem cells, tumor plasticity, circulating tumor cells, and the interplay between tumor cells and the immune system. He is a Fellow of the American Association for the Advancement of Science, an American Cancer Society Research Scholar, and a V-Scholar of the Jimmy V Foundation for Cancer Research.

Current Positions

  • Dean’s Professor of Translational Oncology, Warren Alpert Medical School, Brown University
  • Professor, Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, 2022–present
  • Associate Director for Translational Oncology, Legorreta Cancer Center, Brown University, 2022–present
  • Director, Translational Research Disease Groups, Warren Alpert Medical School, Brown University, 2022–present
  • Director, Stem Cell Center, Warren Alpert Medical School, Brown University, 2022–present

Education

  • BS, Madurai Kamaraj University, India, 1991
  • MS, Madurai Kamaraj University, India, 1993
  • PhD, Indian Institute of Science, Bangalore, India, 2000

Research Activity

  • Epithelial-mesenchymal transition (EMT) and cancer metastasis: Pioneering contributions to understanding how aberrant activation of the embryonic EMT program renders cancer cells migratory, invasive, and metastatic; co-discoverer of FOXC2 as a key regulator of metastasis and aggressive basal-like breast cancers (PNAS, 2007); co-author of the landmark paper demonstrating that Twist plays an essential role in tumor metastasis (Cell, 2004); established EMTome, a pan-cancer resource for EMT gene and signature analysis (British Journal of Cancer, 2020)
  • EMT and cancer stem cells: Demonstrated that the EMT program generates cells with cancer stem cell (CSC) properties in the landmark Cell 2008 paper — one of the most highly cited publications in cancer biology — providing a mechanistic basis for tumor plasticity, metastatic competence, and therapy resistance; ongoing work on enrichment methods, mammosphere formation assays, and limiting dilution assays for CSC quantification
  • Hybrid EMT phenotypes and tumor plasticity: Characterized the partial/hybrid EMT states (neither fully epithelial nor fully mesenchymal) and their significance for metastasis, stemness, and drug resistance; co-author of international EMT guidelines and definitions (Nature Reviews Molecular Cell Biology, 2020; author correction 2021)
  • FOXC2 in metastasis and cancer stem cells: Identified FOXC2 as an essential regulator of EMT-associated stem cell properties in breast cancer (Cancer Research, 2013); FOXC2 regulates the G2/M transition in stem cell-rich breast cancers and sensitizes them to PLK1 inhibition (Scientific Reports, 2016); FOXC2 inhibition restores epithelial phenotype and drug sensitivity in prostate cancer (Oncogene, 2016)
  • GD3 synthase and gangliosides in metastasis: Identified GD3 synthase as a regulator of EMT and metastasis in breast cancer (Oncogene, 2015); GD2 and GD3 synthase as novel drug targets (Molecular & Cellular Oncology, 2015); GD2 identifies breast cancer stem cells and promotes tumorigenesis (Journal of Clinical Investigation, 2012)
    p38 MAPK and cancer stem cells: Characterized the role of p38 MAP kinase in cancer stem cells and metastasis (Oncogene, 2022)
  • Tumor-immune microenvironment: Demonstrated that CD8+ T cells inhibit metastasis and that CXCL4 regulates T cell function (British Journal of Cancer, 2021); studies on targeting the interplay between EMT and the immune system for immunotherapy (Cancers, 2019)
  • Circulating tumor cells and EMT: Co-authored review on CTCs in the omics era (British Journal of Cancer, 2022); EMT-to-mesenchymal plasticity in CTC lines derived from colorectal cancer patients (Cancers, 2021)
  • Single-cell transcriptomics and EMT heterogeneity: Identification of EMT signaling cross-talk and gene regulatory networks by single-cell RNA sequencing (PNAS, 2021); single-cell cloning of breast cancer cells secreting specific subsets of extracellular vesicles (Cancers, 2021)
  • EMT and metabolic reprogramming: Demonstrated that the EMT promotes glutamine independence by suppressing GLS2 expression (Cancers, 2019); EMT-induced metabolite signature identifies poor clinical outcome (Oncotarget, 2015)
  • Cancer dormancy: Co-author on study demonstrating that epithelial-mesenchymal plasticity determines ER-positive breast cancer dormancy and that epithelial reconversion drives recurrence (Nature Communications, 2022)
  • Vimentin as a therapeutic target: Co-author on a vimentin-binding small molecule that leads to mitotic disruption in mesenchymal cancers (PNAS, 2017); vimentin and cytokeratin in cancer biology (Seminars in Cancer Biology, 2022)
  • EMT in aggressive variant neuroendocrine prostate cancer: Characterized EMT, stemness, and tumor plasticity in aggressive neuroendocrine prostate cancers (Biochimica et Biophysica Acta, 2018)
  • Epigenetics and EMT: Demonstrated epigenetic silencing of miR-203 as required for EMT and cancer stem cell properties (Scientific Reports, 2013); KDM6A-mediated H3K27me3 demethylation and bivalency resolution during MET (Oncotarget, 2017)
  • Forkhead box transcription factors: Review of FOXC2 and other forkhead box transcription factors as double-edged swords in cancer (Cancer Research, 2022)
  • Mechanisms of cancer metastasis: Comprehensive review of mechanisms of cancer metastasis (Seminars in Cancer Biology, 2022)
  • EV secretion in metastatic breast cancer: Identifying signatures of EV secretion in metastatic breast cancer through functional single-cell profiling (iScience, 2023)

Honors and Awards

  • Fellow, American Association for the Advancement of Science (AAAS), 2020–present
  • Full Member, Sigma Xi, The Scientific Research Honor Society, 2021–present
  • Dr. Sir A.L. Lakshmanaswami Mudaliar Endowment Lecture, 2021
  • American Cancer Society Research Scholar, 2012–2015
  • Fellow, MD Anderson Research Trust, MD Anderson Cancer Center, 2008–2014
  • V-Scholar, The Jimmy V Foundation for Cancer Research, 2008–2011

Areas of Specialization

  • Epithelial-mesenchymal transition (EMT) in cancer
  • Cancer stem cells and tumor plasticity
  • Breast cancer metastasis and drug resistance
  • Hybrid EMT phenotypes and partial EMT states
  • Circulating tumor cells and single-cell analysis
  • FOXC2, GD3 synthase, vimentin, and p38 MAPK in metastasis
  • Tumor-immune microenvironment and immunotherapy
  • Single-cell transcriptomics, genomics, and epigenomics
  • Translational oncology and precision medicine
  • Cancer dormancy and tumor relapse

Publications

Dr. Mani has authored and co-authored publications in Cell, Nature Communications, Nature Reviews Molecular Cell Biology, PNAS, Journal of Clinical Investigation, Oncogene, British Journal of Cancer, Cancer Research, Seminars in Cancer Biology, Blood, iScience, JACC CardioOncology, and many others.

Select Publications:

Mani SA, Guo W, Liao M-J, 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):704–715, 2008. [Landmark paper]

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, 2004.

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.” PNAS 104(24):10069–10074, 2007.

Yang J, Antin P, Berx G, Blanpain C, Brabletz T, Bronner M, Mani SA, Weinberg RA, et al. (EMT International Association). “Guidelines and definitions for research on epithelial-mesenchymal transition.” Nature Reviews Molecular Cell Biology 21(6):341–352, 2020.

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.” PNAS 107(35):15449–15454, 2010.

Deshmukh AP, Vasaikar SV, Tomczak K, Tripathi S, den Hollander P, Arslan E, Chakraborty P, Soundararajan R, Jolly MK, Rai K, Levine H, Mani SA. “Identification of EMT signaling cross-talk and gene regulatory networks by single-cell RNA sequencing.” PNAS 118(19), 2021.

Kuburich NA, den Hollander P, Mani SA. “Role of p38 MAP kinase in cancer stem cells and metastasis.” Oncogene 41(23):3177–3185, 2022.

Castaneda M, den Hollander P, Kuburich NA, Rosen JM, Mani SA. “Mechanisms of cancer metastasis.” Seminars in Cancer Biology 87:17–31, 2022.

Kuburich NA, den Hollander P, Pietz JT, Mani SA. “Vimentin and cytokeratin: Good alone, bad together.” Seminars in Cancer Biology 86(Pt 3):816–826, 2022.

Castaneda M, den Hollander P, Mani SA. “Forkhead Box Transcription Factors: Double-Edged Swords in Cancer.” Cancer Research 82(11):2057–2065, 2022.

Visal TH, den Hollander P, Cristofanilli M, Mani SA. “Circulating tumour cells in the -omics era: how far are we from achieving the ‘singularity’?” British Journal of Cancer 127(2):173–184, 2022.

Aouad P, Zhang Y, De Martino F, Stibolt C, Ali S, Ambrosini G, Mani SA, Maggs K, Quinn HM, Sflomos G, Brisken C. “Epithelial-mesenchymal plasticity determines estrogen receptor positive breast cancer dormancy and epithelial reconversion drives recurrence.” Nature Communications 13(1):4975, 2022.

Vasaikar SV, Deshmukh AP, den Hollander P, Addanki S, Kuburich NA, Kudaravalli S, Joseph R, Chang JT, Soundararajan R, Mani SA. “EMTome: a resource for pan-cancer analysis of epithelial-mesenchymal transition genes and signatures.” British Journal of Cancer 124(1):259–269, 2020.

Joseph R, Soundararajan R, Vasaikar S, Yang F, Allton KL, Tian L, den Hollander P, Isgandarova S, Haemmerle M, Mino B, Zhou T, Shin C, Martinez-Paniagua M, Sahin AA, Rodriguez-Canales J, Gelovani J, Chang JT, Acharya G, Sood AK, Wistuba II, Gibbons DL, Solis LM, Barton MC, Varadarajan N, Rosen JM, Zhang XH, Mani SA. “CD8+ T cells inhibit metastasis and CXCL4 regulates its function.” British Journal of Cancer 125(2):176–189, 2021.

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 Research 73(6):1981–1992, 2013.

Sarkar TR, Battula VL, Werden SJ, Vijay GV, Ramirez-Peña EQ, Taube JH, Chang JT, Miura N, Porter W, Sphyris N, Andreeff M, Mani SA. “GD3 synthase regulates epithelial-mesenchymal transition and metastasis in breast cancer.” Oncogene 34(23):2958–2967, 2015.

Bollong MJ, Pietilä M, Pearson AD, Sarkar TR, Ahmad I, Soundararajan R, Lyssiotis CA, Mani SA, Schultz PG, Lairson LL. “A vimentin binding small molecule leads to mitotic disruption in mesenchymal cancers.” PNAS 114(46):E9903–E9912, 2017.

Fathi M, Martinez-Paniagua M, Rezvan A, Montalvo MJ, Mohanty V, Chen K, Mani SA, Varadarajan N. “Identifying signatures of EV secretion in metastatic breast cancer through functional single-cell profiling.” iScience 26(4):106482, 2023.

Satpathy S, Krug K, Jean Beltran PM, Savage SR, Petralia F, Kumar-Sinha C, Mani SA, et al. (Clinical Proteomic Tumor Analysis Consortium). “A proteogenomic portrait of lung squamous cell carcinoma.” Cell 184(16):4348–4371.e40, 2021.

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):1015–1028, 2012.

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.” Journal of Clinical Investigation 122(6):2066–2078, 2012.

Soundararajan R, Paranjape AN, Maity S, Aparicio A, Mani SA. “EMT, stemness and tumor plasticity in aggressive variant neuroendocrine prostate cancers.” Biochimica et Biophysica Acta — Reviews on Cancer 1870(2):229–238, 2018.

Jolly MK, Mani SA, Levine H. “Hybrid epithelial/mesenchymal phenotype(s): The ‘fittest’ for metastasis?” Biochimica et Biophysica Acta — Reviews on Cancer 1870(2):151–157, 2018.

All information is sourced from publicly available materials.