Scientist Profile

Sharmila Bapat, Ph.D.

The research theme in my lab relates to elucidation of cellular and molecular pathways underlying ovarian cancer.
Email

sabapat@nccs.res.in

Research Areas

Biology of Cancer and chronic Diseases, Genome Architecture and Regulation

Education and Experience

2001-present, Principal Investigator, National Centre for Cell Sciences, Pune, India

1987-1992, Ph.D (Biochemistry), Pune University

1985-1987, M.Sc (Microbiology), Pune University

Research

We have several achievements in the field including -

  • Identification of quiescent, regenerative human ovarian cancer stem cells (CSCs) through development of unique experimental models, self-renewal assays with stemness-specific molecular correlates, and resolving CSC-niche interactions to study the associations with neo-angiogenesis, aneuploidy and tumor dormancy. 

  • Demonstration that the Epithelial to Mesenchymal Transition (EMT) transcription factors Snail and Slug, which mediate tissue homeostasis following wound healing of normal ovarian surface epithelia, are harnessed for metastatic dissemination in HGSC.

  • A fortuitous study of the intersection of these two phenomena (CSCs and EMT) uniquely revealed that the stress-triggered, non-canonical modulation of EMT leads to CSC enrichment and resistance to p53-mediated apoptosis. 

  • Resolution of intra-tumor heterogeneity as discrete cell fractions reflecting on CSC hierarchies, genetic instability and differential cell cycling.  This identified residual regenerative end-points based on tumor cell dynamics with improved application in drug screening and identification of drug recalcitrance/resistance over  conventional evaluation of tumor volumes following drug exposure.

  • Resolution of inter-tumor heterogeneity vis-à-vis identification of discrete molecular HGSC tumor classes, each with unique regulatory networks, pathways and modes of metastases. Clinical validation of these further revealed transcriptional heterogeneity mediating class-switching (cellular plasticity) following chemotherapy.

  • A deeper molecular understanding of the clinically identified tumor cell plasticity identified auto- and cross-regulation of Slug by TCF21.  These transcription factors map an epithelial (E) to mesenchymal (M) gradient in HGSC, comprising of E, intermediate E, E-M hybrid, intermediate M, and M phenotypes, which correlate with the clinical findings.  Modelling this gradient in vitro achieved a salient comprehension of differential migratory modes (cooperative cell migration and EMT) along the E to M axis, which reflects on the various molecular cross-talks mediating tumor cell survival and drug resistance.

  • Development of a cytotoxic monoclonal antibody specific for the EMT tumor subtype of HGSC.

Our efforts in elucidating the basic biology and regulatory mechanisms in this disease has revealed tumors as dynamically evolving systems that continuously acquire phenotypic, cellular, molecular and functional heterogeneity. 

 

 

Our current research is very exciting and relates to the identification of chimeric transcripts in ovarian cancer.  These represent non-canonical flow of genetic information that remains unexplored in view of molecular diversity that could contribute to definitive cellular functions and therapy in the case of cancer.

 

We are currently being studied for their role in regulating cellular functions.  Using a customized peptide database and a pipeline for their detection, we have been able to identify several chimeric proteins, which are being studied further.  Some of these potentially generate antigenic neoepitopes that is exciting since such neoantigens may be targeted through immunotherapy.

 

 

 

Publications - as Group Leader at NCCS

 

Publications   Patents  Books and Book Chapters   

 

 

Publications

 

Dixit VM, Wagle Arpita K, Bapat SA. Identification of cryptic neoepitopes generated by chimeric transcripts in ovarian cancer (under review).

Singh DK, Shivalingappa PKM, Sharma A, Mondal A, Muzumdar D, Shiras A, Bapat SA - NSG-70, a new glioblastoma cell line with mixed proneural-mesenchymal features associates NOTCH1-WNT5A signaling with stem cell maintenance and angiogenesis. J Neuro-Oncology 2022 May;157(3):575-591. doi: 10.1007/s11060-022-04002-x. Epub 2022 Apr 17.

Kalra RS, Soman GS, Naik RR, Varankar SS, Kamble SC, Mali AM, Parab PB, Bapat SA. A Monoclonal Antibody against Annexin II targets stem and progenitor cell fractions in tumors. Transl Oncol. 2022 Jan;15(1):101257.

Shivalingappa PKM, Sharma V, Shiras A, Bapat SA. RNA Binding Motif 47 (RBM47): Emerging Roles in Vertebrate Development, RNA Editing and Cancer. Mol Cell Biochem. 2021 Dec;476(12):4493-4505.

Varankar SS, More MM, Abraham A, Kumar B, Narayanan NJ, Jolly MK, Bapat SA - Functional Balance between TCF21-Slug defines phenotypic plasticity and migratory modalities in high-grade serous ovarian cancer cell lines; Carcinogenesis. 2020 Jun 17;41(4):515-526./li>

Varankar SS, Bapat SA. Uncoupling Traditional Functionalities of Metastasis: The Parting of Ways with Real-Time Assays. J Clin Med. 2019 Jun 28;8(7). pii: E941.

Kamble SC, Sen A, Dhake RD, Joshi AN, Midha D, Bapat SA. Clinical Stratification of High-Grade Ovarian Serous Carcinoma Using a Panel of Six Biomarkers. J Clin Med. 2019 Mar 8;8(3). pii: E330. doi: 10.3390/jcm8030330.

Jolly MK, Somarelli JA, Sheth M, Biddle A, Tripathi SC, Armstrong AJ, Hanash SM, Bapat SA, Rangarajan A, Levine H. Hybrid epithelial/mesenchymal phenotypes promote metastasis and therapy resistance across carcinomas. Pharmacol Ther. 2019 Feb;194:161-184.

Varankar SS, Bapat SA. Migratory Metrics of Wound Healing: A Quantification Approach for in vitro Scratch Assays. Front Oncol. 2018 Dec 18;8:633. doi: 10.3389/fonc.2018.00633. eCollection 2018.

Naik RR, Singh AK, Mali AM, Khirade MF, Bapat SA. A tumor deconstruction platform identifies definitive end-points in the evaluation of drug responses. Oncogene, 2015 doi: 10.1038 / onc. 2015.130. [Epub ahead of print] PMID:25915841.

Khirade MF, Lal G, Bapat SA. Derivation of a fifteen gene prognostic panel for six cancers. Scientific Reports, 2015; 5:13248.

Kumar B, Uppuladinne MVN, Jani V, Sonavane U, Joshi RR, Bapat SA. Auto-regulation of SNAI2 mediates its activity during epithelial to mesenchymal transition. Biochim Biophys Acta. 2015; 1849: 1209-1219

Singh AK, Chandra N, Bapat SA. Evaluation of epigenetic drug targeting of heterogenous tumor cell fractions using potential biomarkers of response in ovarian cancer. Clinical Cancer Research, 2015; 21: 5151–63.

Gardi NL, Deshpande TU, Kamble SC, Budhe SR, Bapat SA. Discrete Molecular Classes of Ovarian Cancer Suggestive of Unique Mechanisms of Transformation and Metastases. Clinical Cancer Research, 2014, 20 (1): 87 - 99.

Kalra RS, Bapat SA. Expression Proteomics Predicts Loss of RXR- during Progression of Epithelial Ovarian Cancer. PLoS One., 8, 2013; pp:e70398.

Kalra RS, Bapat SA. Enhanced levels of double-strand DNA break repair proteins protect ovarian cancer cells against genotoxic stress-induced apoptosis. J Ovarian Res., 6, 2013; pp 66.

Bapat SA, Jin V, Berry N, Balch C, Sharma N, Kurrey N, Zhang S, Fang F, Lan X, Li M, Kennedy B, Bigsby RM, Huang T H-M, Nephew KP. Multivalent Epigenetic Marks Confer Microenvironment-Responsive Epigenetic Plasticity to Ovarian Cancer Cells. Epigenetics 2010 ; 5(8):1-14.

Bapat SA, Krishnan A, Ghanate AD, Kusumbe AP, Kalra RS. Gene Expression - Protein Interaction Systems Network Modeling identifies Transformation Associated Molecules and Pathways in Ovarian Cancer. Cancer Research. 2010 Jun 15;70(12):4809-19.

Bapat SA. Human Ovarian Cancer Stem Cells. Reproduction, July 2010;140(1):33-41.

Bapat SA. Modulation of Gene Expression in Ovarian Cancer by Active and Repressive Histone Marks. Epigenomics 2010 Feb 10 ; 2(1):39-51.

Kusumbe AP, Bapat SA. Cancer stem cells and aneuploid populations within developing tumors are the major determinants of tumor dormancy. Cancer Res. 2009;69(24):9245-53.

Kurrey NK, Jalgaonkar SP, Joglekar AV, Ghanate AD, Chaskar PD, Doiphode RY, Bapat SA. Snail and Slug mediate radio- and chemo-resistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Stem Cells. 2009 27(9):2059-2068.

Kusumbe AP, Mali AM, Bapat SA. CD133 expressing Stem Cells associated with Ovarian Metastases establish an Endothelial Hierarchy and contribute to Tumor Vasculature. Stem Cells. 2009. Mar;27(3):498-508.

Berry NB, Bapat SA, Ovarian cancer plasticity and epigenomics in the acquisition of a stem-like phenotype. J Ovarian Res.2008 Nov 24; 1(1):8.

Bapat SA. Evolution of cancer stem cells. Semin Cancer Biol. 2007; 17:204-13.

Balch C, Nephew KP, Huang TH, Bapat SA. Epigenetic "bivalently marked" process of cancer stem cell-driven tumorigenesis. Bioessays. 2007 Sep;29(9):842-5.

Wani AA, Sharma N, Shouche YS, Bapat SA. Nuclear-mitochondrial genomic profiling reveals a pattern of evolution in epithelial ovarian tumor stem cells. Oncogene. 2006 12; 25:6336-44.

Bapat SA and Mishra GC. Stem Cell Pharmacogenomics: A Reality Check on Stem Cell Therapy; Curr. Opin. Mol. Ther. 2005; 7(6):551-6.

Bapat SA and Galande S. Association by guilt: identification of DLX5 as a target for MeCP2 provides a molecular link between genomic imprinting and Rett syndrome. Bioessays 2005; 27(7), 676-680

Bapat SA, Mali AM, Koppikar CB, Kurrey NK. Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Research. 2005; 65:3025-9.

Kurrey NK, K A, Bapat SA. Snail and Slug are major determinants of ovarian cancer invasiveness at the transcription level. Gynecol Oncol. 2005; 97:155-65.

Bapat SA & Mishra GC. Stem Cell Pharmacogenomics, Current Topics in Medicinal Chemistry 2004; 4(13): 1371-83.

 

Patents Sealed

US Patent # 20170067901 – “A Tumor Deconstruction Platform for the analysis of Intra-Tumor Heterogeneity”.

Indian Patent # 358225 - “A Tumor Deconstruction Platform for the analysis of Intra-Tumor Heterogeneity”.

Indian Patent # 374150 - “A Monoclonal Antibody Targeting the Tumor Regenerative Hierarchy”.

 

Books - Edited a book – “Cancer Stem Cells” (Publishers: John Wiley & Sons, Hoboken)

Select Book Chapters (after 2015)

Suresh A, Naik RR, Bapat SA. Role of Cancer Stem Cells in Oral Cancer, In: Contemporary Oral Oncology, 2016, Kuriokose (Ed.), Elsevier Publishers.

Panda Suchismita, Shiras A, Bapat SA. Long Noncoding RNAs: Insights into their roles in normal and Cancer Stem Cells, In: Cancer and Non-coding RNAs, 2016, Chakrabarti (Ed.), Elsevier Publishers.

Bapat SA. Tumor.  Initiating Cells in Ovarian Cancer, In: Cell Biology of the Ovary, 2018, Katabuchi H, Ohba T, Motohara T. (eds) Springer, Singapore.

Rajkumar Kalra, Bapat SA. Proteomics to predict loss of RXR-γ during progression of epithelial ovarian cancer. In : Methods in Molecular Biology, Vol. retinoid and Rexinoid Signaling, 2018 Swapan K. Ray (Editor), Springer Nature Press

 

Sharmila A. Bapat (Editor)
Hardcover

 

Awards and Recognitions

2019 – 2020 Short Term ICMR-DHR International Fellowship for Senior Indian Biomedical Scientists

2017 – 2022 TATA Innovation Fellowship from the Department of Biotechnology

2016 Outreach Lecture Fund Award of United States International Education Fund (USIEF)

2016 $10,000 cloud credits from the Cancer Genomics Cloud

2015 – 2016 Fulbright-Nehru Academic and Professional Excellence Award

2015 The Cytometry Society (TCS) Award

2010 R.M. Tiwari Research Oration Award

2008 National Woman Bioscientist Award from the Department of Biotechnology

2007 Prem Nath Wahi Award from the Indian Council for Medical Research

2006 – 2007 Department of Biotechnology Overseas Fellowship

2005 Department of Biotechnology International Travel Award

 

 

Honors/ Appointments

 

2022 – 2025 Chairperson, Cancer Disease Biology Program (TEC) of the Department of Biotechnology

2022 – 2025 Chief Vigilance Officer, NCCS

2015 Elected Fellow of the Indian Academy of Sciences, Bangalore

2015 Elected Fellow of the Maharashtra Academy of Sciences, Pune

2010 Elected Fellow of the National Academy of Sciences, Allahabad

2022 – 2025 Council Member, Indian Academy of Sciences (second term)

2021 – present Member, External Advisory Board, Global Cancer Consortium

2019 – 2022 Council Member, Indian Academy of Sciences

2019 – 2022 Member, Board of Governors, National Institute of Technology, A.P

2019 – 2021 Executive Committee Member of the Indian Association of Cancer Research

2018 – 2022 Member, Board of Studies, Homi Bhabha National Institute (HBNI University)

2018 – 2022 Member, Rapid Action Plan and Scientific Advisory Committee, NII, Delhi

2016 – 2018 Member, AACR Advisory Subcomittee on India

 

 

Memberships

 

Life Member of Indian Association of Cancer Research (IACR)

Life Member of Indian Society of Cell Biology (ISCB)

Member- International Epigenetics Society (earlier DNA Methylation Society)

Life Member of Indian Women Scientists Association.

Life Member of International Federation of Head and Neck Oncology (Honorary Membership received from the foundation)

Elected member of Guha Research Council, India.

Talks / Invited Lectures

(2018 – 2020)

Invited Lectures 

Symposia / Workshops Organised

  1. 2-day Science Academies Lecture workshop on ‘Advances in Cancer Biology’ convened at Sri Ram Narayan Kedia Government Degree College, Desaipet, Banswada, Telangana, on February 27th–28th, 2018.

  2. One-day symposium on “Stem Cells & Cancer – India 2018” at Somaiya Vidyavihar Campus, Mumbai on 5th February, 2018 on behalf of NCCS, along with Sathgen Biotech, Mumbai.

  3. Public talk of Prof. Michael Clarke titled ‘Molecular Regulation of normal and malignant stem cells’ at NCCS, Pune on 6th February, 2018.

  4. NCCS Retreat on 26th – 27th September, 2018 for staff, students and faculty of NCCS at Lonavala.

  5. Organised One-day Indo-Australian symposium on “Epithelial to Mesenchymal Transition” at NCCS on 24th October, 2018 in collaboration with Queensland University of Technology (QUT), Brisbane, Australia and Institute for Bioinformatics (IOB), Bangalore, India; funded by the Australia India Council.

  6. Organised One-day symposium on “Stem Cells & Cancer – India 2018” at Somaiya Vidyavihar Campus, Mumbai on 1st February, 2019 on behalf of NCCS, along with Sathgen Biotech, Mumbai.

 

Talks / Invited Lectures (2017 – 2021)

  1. “Cancer Stem cells in tumor heterogeneity : therapeutic implications” at “Oral Cancer Science Symposium”, held during the 6th World Oral Cancer Congress of the International Academy of Oral Oncology (IAOO) at Bangalore, India

  2. “Phenotypic plasticity along the Epithelial-Mesenchymal Axis in ovarian cancer” at one-day symposium “Epithelial-Mesenchymal Transition – New Advances in Cancer Development” at IISC, Bangalore on 6th October, 2017

  3. “Cellular Phenotypes in Cancer” -.White board talk at Guha Research Council meeting Phenotypic plasticity along the Epithelial-Mesenchymal Axis in ovarian cancer at the 8th Int. EMT meeting (TEMTIA) at MD Anderson Cancer Centre, Houston, US

  4. ‘Science for human welfare’, and ‘Recent Concepts in Cancer Biology’. 2 talks at ASM’s CSIT, Junior College in Pimpri

  5. “Cancer Metastases” at the ICMR funded ROME workshop for clinical and medical practitioners conducted by the Moving Academy of Medicine.

  6. ‘Cancer Development, Drug Resistance and Cancer Stem Cells’ and ‘Cancer Metastases’ – 2 talks at Sri Ram Narayan Kedia Government Degree College, Desaipet, Banswada, Telangana

  7. “Novel Transcripts and Proteins in Tumors” at the Cancer Meeting on Mechanisms of Neoplasia and Precision Medicine in Oncology at National Centre for Biological Sciences, Bengaleru

  8. “Chimeric transcripts and peptides - mediating complexity through diversity” in the 15th Indo-Australian Biotechnology Conference on Contemporary strategies for the prevention and management of disease in the 2020s at The University of Adelaide Medical School, Adelaide Health and Medical Sciences, Adelaide, South Australia

  9. “CSCs and phenotypic plasticity in metastasis” in the 2nd MVR CANCON 2019 at Kozhikode, Kerala

  10. “A decade of association with TCGA ovarian cancer datasets” in the 1st TCGA India 2019 conference at IISER, Pune

  11. “Read through Chimeric Transcripts in Ovarian Cancer” in the one-day Symposium on Molecular Genetics and Cancer at the Department of MRDG, IISc, Bangalore

  12. “Read through Chimeric Transcripts in Ovarian Cancer” in the one-day Symposium on Molecular Genetics and Cancer at the Department of MRDG, IISc

  13. Invited talk titled “Modeling human high-grade serous ovarian cancer in immune compromised mouse models” in the 9th International conference of LASA India at IISER, Pune

  14. “Chimeric transcripts and peptides - mediating complexity through diversity” at the Institute for Systems Genetics, NYU School of Medicine, New York, USA

  15. “Chimeric transcripts and peptides - mediating complexity through diversity” at the Institute of Bioinformatics and Biotechnology, SPPU, Pune on 7th March, 2020.

  16. Invited talk titled “The different shades of cancer metastases” at the National Chemical Laboratory, Pune

  17. Invited talk titled “symposium on “Recent trends in Biology” on 8th and 9th March 2019 at Department of Zoology, Savitribai Phule Pune University.

  18. “ Cancer Research in India: Challenges / Potential solutions” at the V14H1S4 vertical on Cancer genomics of the Vaishvik Bhartiya Vaigyanik (VAIBHAV) Summit 2020

  19. “Tumor Heterogeneity” at the IACR-SAAC-Global Initiative on Cancer Research, WCRD 2021

Current Lab Members

 

 

Ankita More, SRF
Amruta Jadhav, SRF
Aravindan Narayanan, SRF
Bhagyashree Karmarkar, JRF
Ritika Gupta, JRF
Neharani Das, JRF
Shreya Junnarkar, Project JRF
Vaishnavi Dixit, Project Assistant
Vinay Sannannagari, Project JRF
Mrunal Desai, Master’s Trainee
Riddhi Chowdhary, Master’s Trainee
Avinash Mali, Technical Officer B

 

Lab Alumni

PhD Students

Dr. Nawneet Kurrey
Dr. Neeti Sharma
Dr. Anjali Kusumbe
Dr. Rajkumar Singh Kalra
Dr. Anand Kamal Singh
Dr. Brijesh Kumar
Dr. Rutika Naik
Dr. Swapnil Kamble
Dr. Sagar Varankar
Ms. Madhuri More (Thesis submitted)
Ms. Divya Singh (Thesis submitted)
Mr. Pavan KM Shivalingappa (Thesis submitted)

 

Visiting Scientists

Dr. Nicholas Berry, Indiana University, Bloomington, US
Dr. Pratibha Mishra, AFMC, Pune

 

Opportunities

We are looking for highly motivated future PhD students and postdoctoral fellows who have their own source of funding and are interested in cancer biology, RNA biology and immunology. If our science excites you, please send an email to sabapat@nccs.res.in with your updated CV containing the names of three references along with a statement of purpose.

 


Back
Back to Top