Professor, Division of Molecular Medicine
PhD: Indian Institute of Chemical Biology, 2001
2015-2020 : Associate Professor, Div. of Molecular Medicine, Bose Institute, Kolkata
2010-2015 : Assistant Professor, Div. of Molecular Medicine, Bose Institute, Kolkata
2003-2010 : Post Doctoral Research Fellow, Cleveland Clinic, Cleveland, Ohio, USA
LABORATORY OF TUMOR GLYCOBIOLOGY
Understanding the mechanism of tumorigenesis specifically focussing on the role of glycolipids in tumor growth, progression and metastasis.
Specific Research Focus :
How tumor derived Gangliosides modulate tumor growth, progression and metastasis ?
Targeted Genome Editing tools (TALEN and CRISPR) to study mechanisms in carcinogenesis, focusing primary on unknown functions of genes in cancer
Defining the Epigenetic Landscape underlying the Regulation of ganglioside synthase genes in cancer
Potential Role of microRNAs in ganglioside mediated tumorigenesis
How Tumor Microenvironment contributes to metastasis ?
Division of Molecular Medicine
P-1/12 C.I.T. Scheme VII-M
Kolkata - 700054, India
We ask two basic questions - Why select gangliosides are over-expressed in certain cancers ? and What's the consequence of this over-expression in relation to tumorigenesis ? To adress these, we have taken an all-round approach. Gene silencing as well as molecular cloning and over-expression strategies are utilized to establish the potential role of tumor derived glycosphingolipids in migration as well as invasion of tumor cells. Gene expression profiling suggests a large number of differentially regulated gene sets (DRGs) in response to GM2-synthase knockdown and mechanistic studies reveal a critical role of the integrin signaling pathway to be involved in GM2 mediated tumor cell migration. With an aim to translate these in vitro findings in vivo, targeted genome editing technology by TALEN, as well as CRISPR-Cas9 is used to define the functional role of GM2 in tumorigenesis. Studies indicate that GM2 is involved in epithelial-mesenchymal transition (EMT) by promoting anoikis resistance in tumors. Studies are under way to elucidate the mechanism of GM2 mediated EMT. Finally, we have initiated a study to find out the basis of over-expression of several ganglioside synthase genes in cancer, currently focusing on the regulation of GM2-synthase gene. Very recently, data from our lab showed that the GM2-synthase gene is epigenetically regulated in renal cell carcinoma (RCC or kidney cancer) which may well extend to other cancers as well. In this recent finding, we uncovered a novel mechanism regulating the expression of this oncogene, GM2-synthase at the transcriptional level. On a different note, recent data indicate a potential role of micro RNA in GM2-mediated tumorigenesis.
Banerjee, A., Mahata, B., Dhir, A., Mandal, T.K. and Biswas, K.* Elevated histone H3 acetylation and loss of the Sp1-HDAC1 complex de-repress the GM2-synthase gene in renal cell carcinoma. J. Biol. Chem., 294(3), 1005-1018 (2019).
Dhabal, S., Das, P., Biswas, P., Kumari, P., Yakubenko, V.P., Kundu, S., Cathcart, M.K., Kundu, M., Biswas, K. and Bhattacharjee, A.* "Regulation of monoamine oxidase A (MAO-A) expression, activity, and function in IL-13-stimulated monocytes and A549 lung carcinoma cells." J. Biol. Chem., 293(36), 14040-14064 (2018).
Parida, P.K., Mahata, B., Santra, A., Chakraborty, S., Ghosh, Z., Raha, S., Misra, A.K., Biswas, K.* and Jana, K.* (*Joint corresponding author) Inhibition of cancer progression by a novel trans-stilbene derivative through disruption of microtubule dynamics, driving G2/M arrest, and p53-dependent apoptosis. Cell Death Dis., 9(5), 448 (2018).
Kundu, M, Mahata, B, Banerjee, A, Chakrabarty, S, Debnath, S, Sinha Ray, S, Ghosh, Z and Biswas, K.* Ganglioside GM2 mediates migration of tumor cells by interacting with integrin and modulating the downstream signaling pathway. Biochim Biophys Acta – Mol Cell Res., 1863 (7 Pt A), 1472-1489 (2016).
Mahata, B and Biswas, K*. Generation of stable knockout mammalian cells by TALEN mediated locus specific gene editing. Methods Mol Biol., 1498, 107-120 (2017).
Mahata, B, Banerjee, A, Kundu, M, Bandyopadhyay, U and Biswas, K.* TALEN mediated targeted editing of GM2/GD2-synthase gene modulates anchorage independent growth by reducing anoikis resistance in mouse tumor cells. Scientific Reports, 5 : 9048, 1-12 (2015).
Mahata, B, Biswas, S, Rayman, P, Chahlavi, A, Ko, J, Bhattacharjee, A, Li, YT, Li, Y, Das, T, Sa, G, Raychaudhuri, B, Vogelbaum, MA, Tannenbaum, C, Finke, JH and Biswas, K.* GBM Derived Gangliosides Induce T Cell Apoptosis through Activation of the Caspase Cascade Involving Both the Extrinsic and the Intrinsic Pathway. PLoS One, 10, 1-19 (2015).
Parida, PK, Sau, A, Ghosh, T, Jana, K, Biswas, K, Raha, S and Misra, AK. Synthesis and evaluation of triazole linked glycosylated 18β-glycyrrhetinic acid derivatives as anticancer agents. Bioorganic & Medicinal Chemistry Letters, 24, 3865-3868 (2014).
Biswas, K, Richmond, A, Rayman, P, Biswas, S, Thornton, M, Sa, G, Das, T, Zhang, R, Chahlavi, A, Tannenbaum, CS, Novick, A, Bukowski, R. and Finke, JH. GM2 Expression in Renal Cell Carcinoma : Potential Role in Tumor Induced T cell Dysfunction. Cancer Res, 66, 6816-6825 (2006).
Biswas, K, Bandyopadhyay, U, Chattopadhyay, I, Varadaraj, A, Ali, E. and Banerjee, RK. A novel antioxidant and antiapoptotic role of omeprazole to block gastric ulcer through scavenging of hydroxyl radical. J Biol Chem, 278, 10993-11001 (2003).
Bandyopadhyay, U, Biswas, K, Sengupta, A, Moitra, P, Dutta, P, Sarkar, D, Debnath, P, Ganguly, C.K. and Banerjee, RK. Clinical studies on the effect of Neem (Azadirachta indica) bark extract on gastric secretion and gastroduodenal ulcer. Life Sci, 75, 2867-2878 (2004).
Biswas, S, Richmond, A, Biswas, K, Ko, J, Ghosh, S, Simmons, M, Rayman, P, Rini, B, Gill, I, Tannenbaum, C.S. and Finke, JH. Elevated levels of select gangliosides in T cells from Renal Cell Carcinoma patients is associated with T-cell dysfunction. J. Immunol, 183(8), 5050-5058 (2009).
Chattopadhyay, I, Bandyopadhyay, U, Biswas, K, Maity, P and Banerjee, RK. Indomethacin inactivates gastric peroxidase to induce reactive-oxygen mediated gastric mucosal injury and curcumin protects it by preventing peroxidase inactivation and scavenging reactive oxygen. Free Radical Biology and Medicine, 40, 1397-1408 (2006).
Chahlavi, A, Rayman, P, Richmond, AL, Biswas, K, Zhang, R, Vogelbaum, M, Tannenbaum, C, Barnett, G and Finke, JH. Glioblastomas induce T-lymphocyte death by two distinct pathways involving gangliosides and CD70. Cancer Res, 65(12), 5428-38 (2005).
Raval, G, Biswas, S, Rayman, P, Biswas, K, Sa, G, Ghosh, S, Thornton, M, Hilston, C, Bukowski, R, Finke, JH and Tannenbaum, CS. “TNF-a Induction of GM2 Expression on Renal Cell Carcinomas Promotes T cell Dysfunction. J.Immunol, 178, 6642-6652 (2007).
Rayman, P, Wesa, AK, Richmond, AL, Das, T, Biswas, K, Raval, G, Storkus, WJ, Tannenbaum, CS, Novick, A, Bukowski, R and Finke, JH. Effect of Renal Cell Carcinomas on the Development of Type1 T-Cell Responses. Clinical Cancer Research, 10 (18Pt2), 6360S-6366S (2004).
Chattopadhyay, I, Nandi, B, Chatterjee, R, Biswas, K, Bandyopadhyay, U and Banerjee, RK. Mechanism of antiulcer effect of Neem (Azadirachta indica) leaf extract : effect on H+-K+-ATPase, oxidative damage and apoptosis. Inflammopharmacology, 12, 153-176 (2004).
Biswas, K, Chatterjee, I, Banerjee, RK and Bandyopadhyay, U. Biological activity and medicinal uses of Neem (Azadirachta indica). Current Sci, 82, 1336-1345 (2002).
Bandyopadhyay, U, Biswas, K, Chatterjee,R, Bandyopadhyay, D, Chattopadhyay, I, Ganguly, CK, Chakroborty, T, Bhattacharya, K and Banerjee, RK. Gastroprotective effect of Neem (Azadirachta indica) bark extract through inhibition of H+-K+-ATPase and scavenging of hydroxyl radical. Life Sci, 71, 2845-2865 (2002).View More
- Active Member, American Association for Cancer Research (AACR), from 2016
For Integrated MSc PhD Course
Coordinator, Cell Biology
Coordinator, Molecular and Cellular Biology
PhD Course Work
Coordinator, Cell Signaling and Molecular Medicine
|Aishwarya Ray||Junior Research Fellow||Division of Molecular Medicine||Centenary||0|
|Sanchari Chatterjee||Junior Research Fellow||Division of Molecular Medicine||Centenary||0|
PRESENT GROUP MEMBERS
Dipanwita Mukherjee - Research Associate (DBT-RA)
Shibjyoti Debnath - Senior Research Fellow (SRF)
Abhisek Sarkar - Senior Research Fellow (SRF)
Elora Khamrui - Senior Research Fellow (SRF)
Sounak Banerjee - Senior Research Fellow (SRF)
Subha Ray - Senior Research Fellow (SRF)
Dr. Manjari Kundu - Post Doctoral Fellow (NIH, MARYLAND, USA)
Dr. Barun Mahata - Post Doctoral Fellow (RISE UNIVERSITY, TEXAS, USA)
Dr. Avisek Banerjee - Post Doctoral Fellow (YALE UNIVERSITY SCHOOL OF MEDICINE, USA)
POSITIONS OPEN FOR PhD STUDENTS
Interested Students may apply for the Projects below :
PROJECT 1 : Identifying the Upstream Components/Receptors involved in Ganglioside GM2-mediated Regulation of the Hippo-YAP/TAZ axis in EMT and Metastasis.
Brief Description - Recent reports from our laboratory have established a potential role of the tumor derived glycosphingolipid, GM2 in mediating epithelial-mesenchymal transition (EMT) leading to tumor growth and progression. Preliminary data indicates GM2-mediated inactivation of the critical tumor suppressor pathway, HIPPO and subsequent de-phosphorylation induced nuclear translocation of YAP/TAZ leading to upregulation of the YAP/TAZ-dependent genes, namely, ctgf, cyr61, lox, thbs1 etc. However, the precise signaling and the molecular mechanism leading to GM2-mediated de-activation of the HIPPO signaling is still unknown. Additionally, whether GM2-mediated HIPPO-YAP/TAZ signaling translates functionally to induce EMT and metastasis needs to be investigated. We hypothesize that GM2-dependent de-activation of HIPPO kinases, namely Mst’s and LATs might involve receptor-dependent or independent mechanisms at the cell surface, identification of which will provide an option to regulate GM2-mediated tumorigenesis.
Requirement - Post graduate in any discipline of Life Sciences or Biological Sciences
PROJECT 2 : Identifying the
Role of micro RNAs in the regulation of Ganglioside GM2-mediated tumor growth,
progression and metastasis.
Brief Description - This study, for the first time, focuses on the differential role of gangliosides in the regulation of microRNAs in cancer. In silico analysis of Next Generation Sequencing (NGS) data from exogenously administrated GM2 has revealed a subset of up-regulated and down-regulated miRs. A combined study of transcriptomic data as well as small RNA-seq data has identified four significantly down-regulated tumor suppressor micro RNAs (miRs). Interestingly, bioinformatics prediction, revealed that the 3ʹ-UTR of some of the genes up-regulated in response to GM2-treatment, are potential targets for at least 4 downregulated miRs. The project will primarily focus in identifying and validating these miRs and their targets in response to GM2, using classical molecular biology, biochemistry and cell biological techniques. Targeted genome editing using CRISPR-Cas9 will be used to validate the potential micro RNA targets in relation to GM2-mediated tumorigenic growth and metastasis. Additionally, analysis of the RNA seq as well as the transcriptomic data using bioinformatic tools, will be used to understand the GM2-dependent modulation of miRs and its downstream effect in tumorigenic potential. Developing prediction models for precise detection and diagnosis of cancer.
Requirement - Post graduate in any discipline of Life Sciences, Biological Sciences with a knowledge and keen interest in Bioinformatics, or postgraduate in Bioinformatics/related field with knowledge and keen interest to learn modern
biological wet laboratory techniques.
CALENDER OF LABORATORY EVENTS :
- August 16, 2019 - Avisek Banerjee was awarded his PhD degree from the University of Calcutta
- Sometime in 2019 - Avisek Banerjee left for a postdoctoral position in Yale University School of Medicine, USA.
- Dec 07, 2018 - Avisek Banerjee submitted his PhD thesis titled "Defining The Epigenetic Regulation of Ganglioside Synthase Genes in Cancer".
- Nov 30, 2018 - Manjari Kundu left for a postdoc position in TMC, Kolkata
- Oct 30, 2018 - Barun Mahata left for postdoc in RICE UNIVERSITY, Texas, USA
- Aug 01, 2018 - Sounak Banerjee joined as Junior Research Fellow (UGC)
- Aug 01, 2018 - Subha Ray joined as Junior Research Fellow (UGC)
- Sep 01, 2017 - Elora Khamrui joined as Junior Research Fellow (CSIR)
- June 12, 2017 - Barun Mahata joined as Senior Research Fellow (SRF extended, project)
- May 19, 2017 - Abhisek Sarkar joined as Junior Research Fellow (UGC)
- Apr 28, 2017 - Barun Mahata ( SRF) submitted his PhD thesis titled "Study the role and elucidate the mechanism of tumor derived gangliosides in tumor growth, progression and metastasis in syngenic mouse tumor model"
- Apr 01, 2017 - Manjari Kundu (ext SRF) defended her PhD thesis Viva Voce Examination
- Feb 18, 2017 - Barun Mahata (SRF) awarded the best poster award (1st Prize) at the 20th ADNAT convention held at KIIT, Bhubaneswar during Feb 16-18, 2017
- Jan 10, 2017 - Avisek Banerjee (SRF) awarded best poster award at the 3rd International Conference on PCSMM held at Bose Institute, Kolkata during Jan 8-10, 2017
- Aug 22, 2016 - Manjari Kundu (ext SRF) submitted her PhD thesis titled "Deciphering the role and elucidating the mechanism of tumor derived gangliosides in tumor cell growth, migration, invasiveness and metastasis"
- Nov 30, 2015 - Barun Mahata (SRF) awarded Professor B.B. Biswas Outstanding Student Award 2015
- March 25, 2014 - Shibjyoti Debnath joined as Junior Research Fellow (UGC Adhoc)