Senior Scientist, Division of Molecular Medicine
PhD: Vidyasagar University & W. B. University of Animal & Fishery Sciences, 2004
Research Associate, Immunology and Vaccine Development Unit, National Institute of Cholera & Enteric Diseases (NICED), Kolkata.
Research Associate, Crystallography & Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata.
Postdoctoral Research Associate, Garrison Institute on Aging, Texas Tech
University Health Sciences Center, Lubbock, Texas, USA.
(A) Molecular signaling
involved in patho-physiological action of Environmental pollutants in
Germ cell DNA damage and Sperm line Stem Cell apoptosis in connection to male infertility: possible
protection by natural phytochemicals.
(B) Molecular Mechanisms of Germ/Sperm-line Stem Cell Regulation: Special emphasis on Diabetes and aging.
(C) Cancer chemoprevention with new sulforaphane derivatives: involvement of Wnt/β-catenin signaling.
(D) Microtubular dynamics interfering agent causes apoptosis through endoplasmic reticulum stress pathway and sensitizes the breast cancer cells through AP1 mediated TGFBI over- expression.
(E) Development of the anti-filarial drugs from natural sources: Molecular and cellular approach.
(F) Development of nanoparticle mediated treatment strategy to target NOTCH1 in triple negative breast cancer (TNBC) xenograft model.
(G) Exploration of molecular cross-talk involved in the roadmap to hyperhomocysteinemia- induced pregnancy loss in Polycystic Ovarian Syndrome (PCOS).
Division of Molecular Medicine
P-1/12 C.I.T. Scheme VII-M
Kolkata - 700054, India
A novel sulforaphane derivative SP12 induces apoptosis and prevails paclitaxel resistance through over expression of TGFBI protein.
Extracellular matrix (ECM) proteins including ECM receptors and their counterpart binding proteins have been largely associated with tumor cell progression and metastasis. Transforming growth factor-b-induced (TGFBI or keratoepithelin or βIg-h3), one of the ECM protein which has been implicated in a number of cellular disease processes including angiogenesis, tumor progression and metastasis. TGFBI, a 68-kDa protein contains four conserved fasciclin-1 (FAS1) domains and a C-terminal RGD integrin-binding sequence. TGFBI mediates integrin binding to ECM proteins such as collagen, laminin and fibronectin. TGFBI binding to integrins has been related to the activation of cell proliferation, adhesion, migration and differentiation. This protein is down-regulated various human cancers including Ovarian cancer, lung cancer and breast cancer where it acts a tumor suppressor. Interestingly, we have identified a novel sulforaphane derivative SP12 which induces the over expression of TGFBI in paclitaxel resistant SKOV-3 (ovarian cancer), MCF-7/P (breast cancer) and A549/P (lung cancer) cell lines. As reports suggests that JNK signaling pathway activates during TGFBI over-expression. Treatment of SP-12 showed significant increase in the expression of TGFBI along with c-Jun in above cell lines. On the other hand Malt inspector analysis also revealed probable binding site for c-Jun transcription factor in TGFBI promoter region. So, our first objective is to validate the role of c-Jun transcription factor and JNK/SAPK pathway in SP-12 mediated over expression of TGFBI.Microtubule dynamic interfering agents such as paclitaxel (taxol), docetaxel (taxotere), vinblastine, vincristine and colchicines have been involved in activation of the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) signaling pathway in a variety of human cells actually requires interactions with microtubules. Preliminary experiment with SP12, demonstrated higher expression level of an important ER stress biomarker CHOP/DDIT3/GADD153. Again, ER stress has been reported to be linked with activation of JNK/SAPK pathway. Thus, SP12 mediated activation of JNK/SAPK pathway may have a critical role in ER stress. So, our second objective is to deduce the role of SP12 mediated activation of JNK/SAPK in ER stress dependent apoptosis. A recent report suggests TGFBI over expression sensitizes ovarian cancers to paclitaxel via FAK- and Rho-dependent stabilization of microtubules by binding to integrin-αvβ3. So our third objective is to check the function of SP-12 mediated over expression of TGFBI in paclitaxel sensitivity in paclitaxel resistant cells using paclitaxel and SP-12 in combination.
A microtubular dynamics interfering trans-stilbene derivative compound G drives G2/M arrest, apoptosis and impedes cancer progression.
Resveratrol, a trans –stilbene polyphenolic compound and its synthetic analogs have been widely used bioactive molecules due to their remarkable chemopreventive potential. Here, we have identified a novel resveratrol analog, compound G ((Z)-3-(3, 4-dimethoxyphenyl)-2-(3, 4, 5-trimethoxyphenyl) acrylonitrile which inhibits proliferation of several cancer cell lines in vitro through microtubule depolymerization that induced G2M arrest and consequently leads to apoptotic cell death. Importantly, compound G shows limited cytotoxicity to normal cells as compared to cancer cells. Moreover, insight into the molecular and mechanistic detailed studies we reasoned that compound G induces increase in the expression of pro-apoptotic proteins and decrease in the expression anti-apoptotic proteins that decisively helps the activation of caspase 8, caspase 9, caspase 3, leading to PARP-1 and cell death via intrinsic and extrinsic pathways of apoptosis. More importantly, we also have established the crucial contribution of tumor suppressor protein p53 in compound G mediated apoptosis. Interestingly, the compound G also imparts its anti tumorigenic effect by inhibiting clonogenic property and anchorage independent growth potential of cancer cells. Finally, in vivo study with immune-competent syngeneic mice tumor model shows that administration of compound G is able to impede tumor progression without any side effects. So, our presently studied novel trans-stilbene derivative compound G has tremendous anti-tumorigenic potential and can be added to the current regimes of chemotherapy.
Insulin defective stage of type 2 Diabetes (IDS-T2DM) induced testicular Germ cell death/apoptosis in association with the up-regulation of Nrf2 expression: Ameliorative potential of sulforaphane (SFN) and resveratrol (RES).
Diabetes-induced testicular cell death is due predominantly to oxidative stress. Nuclear factor (erythroid- derived 2)-like 2 (Nrf2) is an important transcription factor in controlling the anti-oxidative system and is inducible by sulforaphane (SFN) and resveratrol (RES). To test whether SFN/RES prevents diabetes-induced testicular germ cell death/apoptosis, an insulin-defective stage of type 2 diabetes (IDS-T2DM) was induced in mice. This was accomplished by feeding them a high-fat diet (HFD) for 3 months to induce insulin resistance and then giving one intraperitoneal injection of streptozotocin to induce hyperglycemia while age-matched control mice were fed a normal diet (ND). IDS-T2DM and ND-fed control mice were then further subdivided into those with or without 3-months SFN/RES treatment. IDS-T2DM induced significant increases in testicular germ cell death/apoptosis presumably through receptor and mitochondrial pathways, shown by increased ratio of Bax/Bcl2 expression and cleavage of caspase-3 and caspase-8 without significant change of endoplasmic reticulum stress (GRP78/CHOP). Diabetes also significantly increased testicular oxidative damage and inflammation (TNFα and NFκB). All of these diabetic effects were significantly prevented by SFN/RES treatment with up-regulated Nrf2 expression. These results suggest that IDS-T2DM induces testicular germ cell death/apoptosis presumably through caspase-8 activation and mitochondria-mediated cell death pathways and also by significantly down-regulating testicular Nrf2 expression and function. SFN/RES up-regulates testicular Nrf2 expression and its target antioxidant expression, which was associated with significant protection of the testis from IDS-T2DM-induced germ cell death.
Diabetes-and Ageing associated decrease in adhesion of Testicular Germ line/Spermatogonial Stem cells to the Niche resulted DNA damage and apoptosis along with disrupted GDNF signaling: Protective role of Sulforaphane with the up-regulation of Nrf2.
Germ-line stem cells (GSCs), which can self-renew and generate differentiated progeny, are unique stem cells in that they are solely dedicated to reproduction and transmit genetic information from generation to generation. Through the use of genetic techniques in Drosophila, Caenorhabditis elegans, and mouse, exciting progress has been made in understanding molecular mechanisms underlying interactions between stem cells and niches. The knowledge gained from studying GSCs has provided an intellectual framework for defining niches and molecular regulatory mechanisms for other adult stem cells. In most stem cell systems, one major GSC signaling pathway has been identified that relies on a signal provided by the niche and received by the germ cells. Mosaic analysis, tissue-specific gene expression assays, and transplantation experiments have determined the tissue dependence of the respective factors. Finally, knockout and overexpression or ectopic expression experiments have been used to examine whether a particular signaling pathway plays an instructive role. The major signaling pathways identified include BMP, JAK/STAT, Notch, and GDNF. More detailed analysis of these and additional signaling pathways has provided insight into intricate regulatory networks. As an increasing amount of information emerges, it is becoming clearer how a balance between self-renewal and differentiation is achieved at the molecular level. In the adult, niche signals, GSC-to-niche adhesion, GSC proliferation, and apoptosis are affected by both external and internal conditions. Diabetes and aging are associated with delay or complete failure in GSC self-renewal in both males and females. The effects of diabetes and aging can be overcome by the expression of niche factors, such as the ligands of the BMP and JAK/STAT pathways, the adhesion molecule E-cadherin, or the cell cycle regulator STRING, a Cdc25 homolog. Interestingly, with diabetes and aging the number of GSCs decreases less than expected, likely due to replacement of lost stem cells by symmetrical division, leading to clonal expansion of a subset of GSCs. If a similar process occurs in mammals, such a clonal expansion could contribute to the accumulation of genomic defects in the progeny of diabetes/aged parents.
Development of nanoparticle mediated treatment strategy to
target NOTCH1 in triple negative breast cancer ( TNBC) Xenograft model
The tumors with estrogen negative, progesterone negative and HER2-negative are known as triple-negative (TN) tumors and account for about 15% of breast tumors. These cells have poor prognostic outcome compared with other types of breast cancer. Treatment of TNBC limited due to the lack of a therapeutic target and as a result, these cells are chemo-resistance. As a matter of fact, Notch signaling pathway also have great role for chemo-resistance. These signaling pathway is a conserved pathway that has been involved in the determination of cell fate and self-renewal of a variety of cancer cells. This possible link between Notch signaling and breast cancer was established and Notch-1 exert an influence in tumor metastasis and proliferation in vivo. It was also shown that the expression of Notch 1 was enriched in triple negative breast cancer cells, where as normal breast cells exhibited very low or no dateable noth1 expression. However, the increased expression of Notch-1 in triple negative breast cancer has been associated with malignant tumor behavior and poor prognosis. To overcome this problem, nanoparticles may be used to deliver the drug in different cancer cells both in vitro and in vivo system. our focus is to delivery of drug loaded chitosan nanoparticles and copper coated chitosan nanoparticles tagged with Notch1 antibody for TNBC therapy. Due to its unique polymeric cationic character, chitosan has been extensively examined for the delivery system. We tried to load several anti-cancer drug such as doxorubicin and methoxtrate with chitosan nanoparticles or metal based nanoparticles such as Cu or Zn coated with chitosan. As mentioned before, there is very good strong correlation between the expression of Noth1 and TNBC. So, our target is to conjugate the Noth1 antibody with these nanoparticles. Initially, we examined the effect of these nanoparticles (both Noth1 conjugated or without Notch1 conjugated) on different sub type of breast cancer cells such as MDA-MB-231 (ER–, PR–, HER2–), MCF-7 (ER+, PR+/–, HER2–), BT-474 (ER+, PR+, HER2+), MDA-MB-453(ER–, PR–, HER2+). Next, we will try to focus on the exact molecular mechanism of cell death. The mouse models of human cancer are valuable tools for cancer research. So, we will also develop the TNBC xenograft model in immunodeficient mouse. The targeted drug or nanodrug delivery through chitosan nanoparticles tagged with Notch1 antibody will be therapeutic approach for treatment of chemo resistant triple negative breast cancer cells. Successful development of these kind of strategy for targeted delivery in TNBC xenograft model has tremendous application for overcome chemo-resistance of TNBC.
Ahir M, Bhattachrya S, Parida PK, Adhikary A, Jana K & Ray M. Induction of Mitochondrial apoptotic pathway in Triple negative Breast carcinoma cells by Methylglyoxal via generation of Reactive oxygen species. Molecular Carcinogenesis, Apr 18, doi:10.1002/mc.22665 (2017)
Sahu SK, Kumar M, Banerjee S, Kumar R, Gupta P, Jana K, Gupta UD, Ghosh Z, Kundu M& Basu J. miR-26a-KLF4 and CREB-C/EBP beta regulate innate immune signaling, the polarization of macrophages and the trafficking of Microbacterium tuberculosis to lysosomes during infection. PLoS Pathogen (2017) (In Press)
Banerjee B, Nandi P, Chakraborty S, Raha S, Sen PC & Jana K. Resveratrol ameliorates Benzo(a)pyrene induced testicular dysfunction and apoptosis through p38MAPK/ATF2/iNOS signalling. The Journal of Nutritional Biochemistry, 34, 17-29 (2016)
Banerjee A, Sanyal S, Dutta S, Chakraborty P, Das PP, Jana K, Vasudevan M, Das C & Dasgupta D. The plant alkaloid Chelerythrine binds to chromatin, alters H3K9Ac and modulates global gene expression. Journal of Biomolecular Structure and Dynamics, 5, 1-9 (2016)
Sirkar G, Jana K, Dasgupta A, Saha S & Gupta Bhattachrya S. Epitope mapping of Rhio 1 and generation of a Hypoallergenic Variant: a candidate molecule for fungal allergy vaccines. The Journal of Biological Chemistry, 291, 18016-18029 (2016)
Banerjee B, Nandi P, Chakraborty S, Raha S, Sen PC & Jana K. Curcumin and resveratrol synergistically prevent Benzo(a)pyrene induced male germ cell apoptosis by modulating MAPKs and p53. Frontiers in Pharmacology, 7, 245 (2016)
Banerjee S, Kumar M, Alokam R, Sharma AK, Chatterje A, Jana K, Singh R, Yogeeswari P, Sriram D, Basu J & Kundu M. Targeting multiple response of Mycobacterium tuberculosis augments the host immune response to infection. Scientific Reports, 6, 25851 (2016)
Ghosh R, Pradhan A, Maity P, Jana K & Maiti Chowdhury S. Lipid peroxidative damage, alteration in antioxidant status and morphological changes in rat erythrocytes on Lambda-cyhalothrin exposure and its attenuation by taurine. Toxicology and Environmental Health Sciences, 8, 315-326 (2016)
Dinda M, Chakraborty M, Ganguly D, Dasgupta U, Dutta A, Jana K & Karmaka P. The water fraction of Calendula Officinalis hydroethanol extract stimulates in vitro and in vivo proliferation of dermal fibroblasts in wound healing. Phytotherapy Research, 10, 1696-1707 (2016)
Roy P, Dhara D, Parida PK, Kar RK, Bhunia A, Jana K & Misra AK. C-cinamoyl glycosides as a new class of anti-filarial agents. European Journal of Medicinal Chemistry, 114, 308-317 (2016)
Mukherjee N, Parida PK, Santra A, Ghosh T, Dutta A, Jana K, Misra AK & Sinha Babu SP. Oxidative stress plays major role in mediating apoptosis in filarial nematode Setaria cervi in the presence of trans-stilbene derivatives. Free Radical Biology and Medicine, 93, 130-144 (2016)
Kumar R, Sahu SK, Kumar M, Jana K, Gupta P, Gupta UD, Kundu M & Basu J. MicroRNA 17-5p regulates autophagy in Microbacterium tuberculosis -infected macrophages by targeting Mcl-1 and STAT3. Cellular Microbiology, 18, 679-691 (2016)
Halder P, Kumar R, Jana K, Chakraborty S, Ghosh Z, Kundu M & Basu J. Gene expression profiling of Microbacterium tuberculosis Lipoarabinomannan-treated microphages: A role of the Bcl-2 family member A1 in inhibition of apoptosis in Mycobacteria-infected macrophages. IUBMB Life, 67, 726-736 (2015)
Kumar M, Sahu SK, Kumar R, Subuddhi A, Maji RK, Jana K, Gupta P, Raffetseder J, Lerm M, Ghosh Z, van Loo G, Beyaert R, Gupta UD, Kundu M & Basu J. Micro RNA let-7 modulates the immune response to Microbacterium tuberculosis infection via control of A20, an inhibitor of the NF-kB pathway. Cell Host & Microbe, 17,345-356 (2015)
Banerjee A, Sanyal S, Majumder P, Chakraborty P, Jana K, Das C & Dasgupta D. Recognition of chromatin by the plant alkaloid, ellipticine as a dual binder. Biochemical and Biophysical Research Communications, 462, 352-357 (2015)
Banerjee A, Sanyal S, Kulkarni KK, Jana K, Roy S, Das C & Dasgupta D. Anticancer drug mithramycin interacts with core histones: An additional mode of action of the DNA groove binder. FEBS Oen Bio, 4, 987-995 (2014)
Firdaus SB, Ghosh A, Chattopadhyay BA, Jana K & Bandopadhyay D. Protective effect of antioxidant rich aqueous curry leaf (Murraya koenigii) extract against gastro-toxic effects of piroxicam in male Wistar rats, Toxicology Reports, 1, 987-1003 (2014)
Jana K, Dutta A, Chakraborty P, Manna I, Firdaus SB, Bandopadhyay D, Chattopadhyay R & Chakravarty B. Alpha-lipoic acid and N-acetylcysteine protects swimming exercise mediated germ cell depletion, pro-oxidant generation and alteration of steroidogenesis in rat testis. Molecular reproduction & Development, 81, 833-850 (2014)
Parida PK, Sau A, Ghosh T, Jana K, Biswas K, Raha S & Misra AK. Synthesis and evaluation of trizole linked glycosylated 18 beta-glycyrrhetinic acid derivatives as anticancer agents. Bioorganic & Medicinal Chemistry Letters 8, 428-436 (2014)
Firdaus SB, Ghosh A, Chattopadhyay BA, Jana K & Bandopadhyay D.A combination of aqueous curry (Murraya koenigii) leaf extract and melatonin protects against piroxicam induced gastric ulcer in male albino rats: involvement of antioxidant mechanism(s), Journal of Pharmacy Research 8, 428-436 (2014).
Roy A, Roy M & Jana K. Cancer stem cells, Wnt, Hedgehog and Notch signaling, the role of dietary phytochemicals: New insights for cancer therapy. Translational Medicine, 3, 1000e125 (2014)
Banerjee A, Majumder P, Singh J, Jana K, Das C & Dasgupta D. DNA intercalators, ethidium bromide and propidium iodide, bind to core histones. FEBS Open Bio, 15, 251-259 (2014)
Chakraborty P, Gos, Sharma S, Kabir SN, Chakravarty BN & Jana K. Recurrent pregnancy loss in poly-cystic ovary syndrome: role of hyper-homocysteinemia and insulin resistance. PLoS One, 8, e64446 (2013)
Jana K, Banerjee B & Parida PK. Caspases: A potential therapeutic targets in the treatment of Alzheimer's disease. Translational Medicine, S2, 006 (2013)
Chakraborty P, Goswami SK, Rajani S, Sharma S, Kabir SN, Chakravarty BN & Jana K. Altered trace mineral milieu might play an aetiological role in the pathogenesis of polycystic ovary syndrome. Biology of Trace Element Research, 152, 9-15 (2013)
Jana K & Samanta PK. Clinical evaluation of non-surgical sterilization of male cats with single intratesticular injection of calcium chloride. BMC Veterinary Research, 7, 39
Nandi P, Charteejee S, Jana K & Sen PC. Role of a 14 KD sperm protein p14 in maturation, acrosome reaction and capacitation of caprine spermatozoa. PLoS One, 7, e30552 (2012)
Kumar R, Halder P, Sahu SK, Kumar M, Kumari M, Jana K, Ghosh Z, Sharma P, Kundu M & Basu J. Identification of a novel role of ESAT-6-dependent miR-155 induction during infection of macrophages with Micobacterium tuberculosis. Cellular Microbiology, 14, 1620-1631 (2012)
Jana K, Samanta PK & De DK. Nicotine diminishes testicular gamatogenesis, steroidogenesis and steroidogenic acute regulatory protein expression in adult albino rats: possible influence on pituitary gonadotrophins and alters testicular antioxidant status. Toxicological Sciences, 116, 647-659 (2010)
Jana K, Jana N, De DK & Guha SK. Ethanol induces mouse spermatogenic cell apoptosis in vivo through over expression of Fas/Fas-L, p53 and caspase-3 along with cytochrome C translocation and glutathione depletion. Molecular Reproduction & Development, 77, 820-833 (2010)
- Young Scientist Travel Award from ACC&D (Portland, Oregeon, U.S.A.), 2010
- DST-First Track Young Scientist Scheme Award, 2010
- Young Investigator Award from Parsemus Foundation (San Francisco, California, USA) , 2011
- International Scientist of the Year, 2011 by IBC (Cambridge, U.K.), 2011
- Scientific Award of Excellence, 2011, ABI (San Francisco, California, USA) , 2011
- Young Scientist (Clinical) Award, 2012 from Parsemus Foundation (San Francisco, California, USA) , 2012
- Outstanding Scientist Award, 2015 from VIF (India), 2015
Special paper classes in Endocrinology & Reproductive Physiology/ Biochemistry (Cell signalling, hormone action, signal transduction, cancer signalling and Immunology) and Environmental Science (Toxicology and pharmacology, Reproductive and Endocrine Disorders etc.) of M.Sc. (Physiology) students of University of Calcutta as well as taking classes of Integrated M.Sc.-Ph.D. courses at Bose Institute.
|Arin Gucchait||JRF||Division of Molecular Medicine||Centenary||aringucchait|
|Bhaswati Banerjee||SRF||Division of Molecular Medicine||Centenaryemail@example.com|
|Kunal Pal||JRF||Division of Molecular Medicine||Centenary|
|Pravat Kumar Parida||SRF(I)||Division of Molecular Medicine||Centenary||25693337||pravat89|
Name of group Members
Pravat Kumar Parida, CSIR-SRF
Bhaswati Banerjee, SRF
Anirban Ray, UGC-SRF
Ananya Dutta, SRF
Kunal Pal, CSIR-JRF
Dr. Dipranjan Laha, DBT-RA
Arin Gucchait, CSIR-JRF
The students who are creative, highly motivated & willing to work in a multidisciplinary scientific projects with a very keen interest to work in Molecular Endocrinology/Reproductive Medicine/Cancer Biology/Toxicology/Animal Biotechnology/Molecular Medicine may contact directly at firstname.lastname@example.orgemail@example.comfirstname.lastname@example.org
or may call me at 9007042850/9007067720