DBT Distinguished Scientist

Manoj Kumar Bhat, Ph.D.

DBT Distinguished Scientist
Email

manojkbhat@nccs.res.in

Education and Experience

Education

  • Ph.D. Biochemistry, 1992, University of Mysore, India
  • M.Sc. Biochemistry, 1985, University of Mysore, India
  • B.Sc. Chemistry, Physics and Mathematics, 1983, University of Mysore, India

 

Professional Experience

DBT Distinguished Scientist, From 2022, National Centre for Cell Science, Pune, India

Director, 2019 to 2022, National Centre for Cell Science, Pune, India

Scientist D to G, 1998 to 2019, National Centre for Cell Science, Pune, India

Research Associate, 1998-1998, Institute of Human Virology, University of Maryland, Maryland

Visiting Fellow, 1993-1998, National Cancer Institute, NIH, Bethesda, MD

Senior Research Fellow, 1990-1992, University of Mysore, India

Junior Research Fellow, 1986-1989, University of Mysore, India

Research

 

Cell Biology and Cancer Biology/Chemotherapy

  • Recent studies have suggested that metabolic disorders like diabetes and obesity alter the risk of developing variety of cancers, and the associations are biologically plausible. With the hypothesis that nutrient availability and insulin signaling pathways are linked to cell proliferation and survival, a greater understanding of the relationship between diabetes/obesity and cancer will lead to innovative avenues of pharmaceutical investigation.
  • The medical need for advances in cancer treatment with surgery, radiotherapy and conventional cytotoxic chemotherapy, have made only a modest overall impact on mortality. Hence the significance of discovering new targets, pathways and strategies for therapeutic intervention in cancer is extremely important. Therefore, understanding the molecular events that contribute or enhance drugs induced cell death will not only help in explaining the relationship between cancer genetics and chemotherapeutic drugs but also will improve sensitivity as well as specificity of the treatment.

Publications

 

Recent Publications (2010-16)   All Publications  Book Chapters  Patents

 

Recent Publications (2010-16)

Singh S, Chouhan S, Mohammad N, Bhat MK. Resistin causes G1 arrest in colon cancer cells through upregulation of SOCS3. FEBS Lett. 2017 May. PMID:28417458 DOI: 10.1002/1873-3468.12655
Khalique, A, Sarwade, R.D., Pandey, P.R., Vijayakumar, M.V., Bhat, M.K. and Seshadri, V.: Prolonged exposure to insulin with insufficient glucose leads to impaired Glut4 translocation. Biochemical and Biophysical Research Communications, 474(1):64-70, (2016), PMID: 27105912 DOI: 10.1016/j.bbrc.2016.04.066
Malvi, P., Chaube, B., Singh, S.K.,Mohammad, N., Pandey, V., Vijayakumar, M.V., Radhakrishnan, R.M., Vanuopadath, M., Nair, S.S., Nair, B.G. and Bhat, M.K.: Weight control interventions improve therapeutic efficacy of dacarbazine in melanoma by reversing obesity-induced drug-resistance. Cancer and metabolism, (2016), PMID: 27980732 DOI: 10.1186/s40170-016-0162-8
Chouhan, S., Singh, S., Ramteke, P., Athavale, D., Pandey, V., Joseph,J., Mohan, R., Shetty, P.K. and Bhat, M.K.: Glucose induced activation of canonical Wnt signaling pathway in hepatocellular carcinoma is regulated by DKK4. Scientific Reports, (2016). PMID: 27272409 DOI: 10.1038/srep27558
Chaube, B. Bhat, M.K.: AMPK, a key regulator of metabolic/energy homeostasis and mitochondrial biogenesis in cancer cells. Cell Death and Disease, 7:e2044, (2016). PMID:26775698 DOI: 10.1038/cddis.2015.404.
Chaube, B., Malvi, P., Singh, S.V., Mohammad, Viollet, B. and Bhat, M.K.: AMPK maintains energy homeostasis and survival in cancer cells under metabolic stress by regulating p38/PGC-1α-mediated mitochondrial biogenesis. Cell Death and Discovery, 1, 15063, (2015). PMID:27551487 doi: 10.1038/cddiscovery.2015.63.
Chaube, B., Malvi, P., Singh, S.V., Mohammad, N., Meena, A.S. and Bhat, M.K.: Targeting metabolic flexibility by simultaneously inhibiting respiratory complex I and lactate generation retards melanoma progression. Oncotarget, 6(35):37281-37299, (2015). PMID:26484566 DOI:10.18632/oncotarget.6134 
Singh, S.V., Ajay, A.K., Mohammad, N., Malvi, P., Chaube, B., Meena, A.V. and Bhat, M.K.: Proteasomal inhibition sensitizes cervical cancer cells to mitomycin C induced bystander effect: The role of tumor microenvironment. Cell Death and Disease,   6:e1934, (2015). PMID:26492368 DOI:10.1038/cddis.2015.292 
Mohammad, N., Singh, S.V., Malvi, P., Chaube, B., Athavale, D.A., Vanuopadath, M., Nair, S.S., Nair, B.G. and Bhat, M.K.: Strategy to enhance efficacy of doxorubicin in solid tumor cells by methyl-β-cyclodextrin: Involvement of p53 and Fas receptor ligand complex. Scientific Reports, 5, 11853, (2015). PMID:26149967 DOI:10.1038/srep11853
Malvi, P., Chaube, B., Pandey, V., Vijayakumar, M.V., Boreddy, P.V., Mohammad, N., Singh, S.V. and Bhat, M.K.: Obesity induced rapid melanoma progression is reversed by orlistat treatment and dietary intervention: role of adipokines.   Molecular Oncology, 9(3):689-703, (2015). PMID:25499031 DOI: 10.1016/j.molonc.2014.11.006.
Malvi, P., Piprode, V., Chaube, B., Pote, S.T., Mittal, M., Chattopadhyay, N., Wani, M.R. and Bhat, M.K.: High fat diet promotes achievement of peak bone mass in young rats. Biochemical and Biophysical Research Communications, 455(1-2):133-8, (2014). PMID:25450704 DOI:10.1016/j.bbrc.2014.10.131
Mohammad, N., Malvi, P., Meena, A.S., Singh, S.V., Chaube, B., Vannuruswamy, G., Kulkarni, M.J and Bhat M.K.: Cholesterol depletion by methyl-β-cyclodextrin augments tamoxifen induced cell death by enhancing its uptake in melanoma. Molecular Cancer, 13:204, (2014). PMID:25178635 DOI: 10.1186/1476-4598-13-204.
Kumar, R., Sinha, A., Vijayakumar, M.V., Pandey, V., Bhide  A., Javadekar, S.S., Pawar, B. and Bhat, M.K.: Population based estimation of mortality and occurrence of cancer in patients with and without diabetes in Pune City. Current Science, 105(4): 486-491 and, In this issue section page 426, (2013).
Meena, AS., Sharma, A., Kumari, R., Mohammad, N., Singh, S.V. and Bhat, M.K.: Inherent and acquired resistance to paclitaxel in hepatocellular carcinoma: Molecular events involved. PLOS One, 8(4):e61524, (2013). PMID:23613870 DOI: 10.1371/journal.pone.0061524.
Kumar, A., Mitra, A., Ajay, A.K., Bhat, M.K. and Rao, C.P.: Cu(II) complexes of glyco-imino-aromatic conjugates in DNA binding, plasmid cleavage and cell cytotoxicity. Journal of Chemical Sciences, 124(6): 1217-1228, (2013).
Parvatkar, P.T., Ajay, A.K., Bhat, M.K., Parameswaran, P.S., Tilve, S.G.: Iodine catalyzed one-pot synthesis of chloro-substituted linear and angular indoloquinolines and in vitro antiproliferative activity study of different indoloquinolines. Medicinal Chemistry Research, 22:88-93, (2013).
Pandey V., Vijayakumar, M.V., Ajay, A.K. Malvi, P. and Bhat, M.K.: Diet induced obesity increases melanoma progression: involvement of Cav-1 and FASN.  International Journal of Cancer, 130(3):497-508, (2012). PMID:21387314 DOI: 10.1002/ijc.26048.
Ajay, A.K., Meena A.S. and Bhat, M.K.: Human papillomavirus 18 E6 inhibits phosphorylation of overexpressed p53 in HeLa cells. Cell and Bioscience, 2:2, (2012). PMID: 22244155DOI: 10.1186/2045-3701-2-2.
Vijayakumar, M.V. and Bhat, M. K.: Real time qualitative and quantitative Glut4 translocation assay. Methods in Enzymology “Imaging and Spectroscopy of Live Cells”, 505:257-71,(2012). PMID: 22289458 DOI: 10.1016/B978-0-12-388448-0.00022-X.
Sharma, A. and Bhat M.K.: Enhancement of Carboplatin and Quercetin Induced Cell Death by Roscovitine is Akt Dependent and p53 Independent in Hepatoma Cells. Integrated Cancer Therapies, 10(4):NP4-14, (2011). PMID: 21994207 DOI: 10.1177/1534735411423922.
Pandey V., Chaube, B. and Bhat, M.K.: Hyperglycemia regulates MDR-1, drug uptake and ROS levels causing increased toxicity of carboplatin and 5-fluorouracil in MCF-7 cells. Journal of Cellular Biochemistry, 112(10):2942-52, (2011). PMID: 21630327 DOI: 10.1002/jcb.23210.
Kumar, A., Chinta, J.P., Ajay, A.K., Bhat, M.K. and Rao, C.P.: Synthesis, characterization, plasmid cleavage and cytotoxicity of cancer cells by a copper(II) complex of anthracenyl terpyridine. Dalton Transactions, 40(41):10865-72, (2011). PMID: 21709916 DOI: 10.1039/c1dt10201j.
Vijayakumar, M.V., Ajay, A.K. and and Bhat, M.K.: Demonstration of a visual cell-based assay for screening glucose transporter 4 translocation modulators in real time. Journal of Biosciences, 35(4):525-31, (2010). PMID: 21289434.
Ajay, A.K, Upadhyay, A.K., Singh S., Vijayakumar, M.V., Kumari, R., Pandey, V., Boppana, R. and Bhat M.K.: Cdk5 Phosphorylates Non-genotoxically Overexpressed p53 following Inhibition of PP2A to Induce Cell Cycle Arrest/apoptosis and Inhibits Tumor Progression. Molecular Cancer, 9:204, (2011). PMID: 20673369 DOI: 10.1186/1476-4598-9-204.
Sharma, A. Meena A.S. and Bhat, M.K.: Hyperthermia associated carboplatin resistance: Differential role of p53, HSF1 and Hsp70 in hepatoma Cells. Cancer Science, 101(5):1186-93, (2010). PMID: 20180806 DOI: 10.1111/j.1349-7006.2010.01516.x.
Shriram, V., Kumar, V., Suryawanshi, S., Upadhyay, A. and Bhat, M.K.: Cytotoxic activity of 9,10-dihydro-2,5-dimethoxyphenanthrene-1,7-diol from Eulophia nuda against human cancer cells. Journal of Ethnopharmacology, 128(1):251-3, (2010). PMID: 20045453 DOI:10.1016/j.jep.2009.12.031.
Vijaykumar, M.V., Pande, V, Mishra, G.C. and Bhat, M.K.: Hypolipidemic effect of fenugreek seeds is mediated through inhibition of fat accumulation and up regulation of LDL receptor. Obesity, 18(4):667-74, (2010). PMID: 19851306 DOI: 10.1038/oby.2009.337

 

Complete list of publications

Kumari, R. Sharma, A., Ajay, A.K. and Bhat, M.K.:Mitomycin C induced bystander killing in homogenous and heterogeneous cell model of hepatoma cellular model. Molecular Cancer, 8:87, (2009). PMID: 19845939 DOI: 10.1186/1476-4598-8-87.
Sharma, A., Upadhyay, A.K. and Bhat, M.K.: Inhibition of Hsp27 and Hsp40 potentiates 5-fluorouracil and carboplatin mediated cell killing in hepatoma cells. Cancer Biology and Therapy, 8(22):2106-2113, (2009). PMID: 19901540.
Aher, N.G., Pore, V.S., Mishra, N.N., Kumar, A., Shukla, P.K., Sharma, A., and Bhat, M.K.: Synthesis and antifungal activity of 1,2,3-triazole containing new fluconazole analogues. Bioorganic Medicinal Chemistry Letters, 19: 759 -763, (2009). PMID: 19110424 DOI: 10.1016/j.bmcl.2008.12.026.
Pandey, V., Vijayakumar, M.V., Kaul-Ghanekar, R., Mamgain, H., Paknikar, K. and Bhat, M.K.: Atomic Force Microscopy, biochemical analysis of 3T3-L1 cells differentiated in the absence and presence of insulin. Biochimica et Biophysica Acta, 1790(1):57 -64, (2009). PMID: 18809467 DOI: 10.1016/j.bbagen.2008.08.008.
Upadhyay, A.K., Ajay, A.K., Singh, S. and Bhat, M.K.: Cell Cycle Regulatory Protein 5 (Cdk5) is a Novel Downstream Target of ERK in Carboplatin Induced Death of Breast Cancer Cells. Current Cancer Drug Targets, 8(8):741-752, (2008). PMID: 19075597.
Vijaykumar, M.V. and Bhat, M.K.: Hypoglycemic effect of dialyzed fenugreek seeds extract is sustainable and is mediated, in part, by the activation of hepatic enzymes. Phytotherapy Research, 22: 500-525, (2008). PMID:15980869DOI: 10.1038/sj.bjp.0706312
Gholap, A. R., Toti, K. S., Shirazi, F., Kumari R., Bhat, M.K., Deshpande, M.V. and Srinivasan K.V.: Synthesis and evaluation of antifungal properties of a series of the novel 2-amino-5-oxo-4-phenyl-5,6,7,8-tetrahydroquinoline-3-carbonitrile and its analogues. Bioorganic and Medicinal Chemistry, 15(21): 6705-6715, (2007). PMID: 17765545 DOI: 10.1016/j.bmc.2007.08.009.
Chhipa, R.R., Kumari, R.Upadhyay, A.K. and Bhat, M.K.: Abrogation of p53 by its antisense in MCF-7 breast carcinoma cells increases cyclin D1 via activation of Akt and promoting cell proliferation. Experimental Cell Research, 15; 313(19): 3945-3958, (2007). PMID: 17935714 DOI: 10.1016/j.yexcr.2007.08.022.
Singh, S., Upadhyay, A.K., Ajay, A.K. and Bhat, M.K.:p53 regulates ERK activation in carboplatin induced apoptosis in cervical carcinoma: A novel target of p53 in apoptosis. FEBS Letters, 581: 289 -295, (2007). PMID: 17208232 DOI: 10.1016/j.febslet.2006.12.035.
Chhipa, R.R. and Bhat, M.K.: Bystander killing of breast cancer MCF-7 cells by MDA-MB-231 cells exposed to 5-fluorouracil is mediated via Fas. Journal of Cellular Biochemistry, 101: 68 -79, (2007). PMID: 17340621 DOI: 10.1002/jcb.21153.
Singh, S., Upadhyay, A.K., Ajay, A.K. and Bhat, M.K.: Gadd45a does not modulate the cytotoxicity of DNA damaging drugs in HPV-positive cells even though it is induced in response to drug treatment. Journal of Cellular Biochemistry, 100: 1191 -1199, (2007).
Upadhyay, A.K., Singh, S., Ajay, A.K. and Bhat, M.K.: Methyl-β-cyclodextrin enhances the susceptibility of human breast cancer cells to carboplatin and 5-fluorouracil: Involvement of Akt, NF-kappaB and Bcl-2. Toxicology and Applied Pharmacology, 216(2):177-185, (2006). PMID: 16806341 DOI: 10.1016/j.taap.2006.05.009.
Singh, S., Chhipa, R.R., Vijayakumar M.V. and Bhat, M.K.: DNA damaging drugs induced downregulation of Bcl-2 is essential for induction of apoptosis in high-risk HPV-positive HEp-2 and KB cells. Cancer Letters, 236 (2): 213-221, (2006). PMID: 15996812 DOI: 10.1016/j.canlet.2005.05.024.
Vijayakumar M.V., Singh, S., Chhipa, R.R. and Bhat, M.K.: Hypoglycemic activity of fenugreek seeds extract is mediated through the stimulation of insulin signaling pathway. British Journal of Pharmacology, 146 (1): 41-48, (2005). PMID: 15980869 DOI: 10.1038/sj.bjp.0706312.
Chhipa, R.R., Singh, S., Surve, S.V., Vijayakumar M.V. and Bhat, M.K.: Doxycycline potentiates antitumor effect of cyclophosphamide in mice. Toxicology and Applied Pharmacology, 202(3):268-277, (2005). PMID: 15667832 DOI: 10.1016/j.taap.2004.06.025.
Singh, S. and Bhat, M.K.: Carboplatin induces apoptotic cell death through downregulation of constitutive activity of nuclear factor-kB in human HPV-18 E6 positive HEp-2 cells. Biochemical and Biophysical Research Communications, 318: 346-353, (2004). PMID: 15120608 DOI: 10.1016/j.bbrc.2004.04.037.
Salunke, D.B., Hazra B.J., Pore V.S., Bhat, M.K., Nahar, P.B. and Deshpande, M.V.: New Steroidal Dimers with Antifungal and Antiproliferative Activity.Journal of Medicinal Chemistry, 47: 1591-1594, (2004). PMID: 14998344 DOI: 10.1021/jm030376y.
Kaul, R., Ahmed, F., Bhat M.K., Chhipa, R., Galande, S. and Chattopadhyay, S.: Direct interaction and activation of p53 by SMAR1 causes cell cycle arrest at G2M phase and delays tumor growth in mice. International Journal of Cancer, 103: 606-615, (2002). PMID: 12494467 DOI: 10.1002/ijc.10881.
Zhu, X-Y., Kaneshige, M., Bhat, M.K., Zhu, Q., Mariash, C.N., McPhie, M. and Cheng, S-Y.: The orphan nuclear receptor Ear-2 is a negative Co-regulator for thyroid hormone nuclear receptor function.Molecular and Cellular Biology, 20(7): 2604-2618, (2000). PMID: 10713182.
Bhat, M.K., Dace A. and Cheng, S-Y.: Tissue -specific differential repression of gene expression by a dominant negative mutant of thyroid hormone β1 receptor. Thyroid, 9(4): 411-418, (1999). PMID: 10319950 DOI: 10.1089/thy.1999.9.411.
Bhat, M.K., Yu, C-l., Yap, N., Zhan, Q., Hayashi, Y., Seth, P. and Cheng, S-y.: The tumor suppressor p53 is a negative regulator in thyroid hormone receptor signalling pathways. Journal of Biological Chemistry, 272: 28989-28996, (1997). PMID: 9360971.
Bhat, M.K., Mcphie, P. and Cheng, S-Y.: The critical role of glutamine 252 in the hormone-dependent transcriptional activity of the thyroid hormone β1 nuclear receptor. Biochemistry, 36: 4233-4239, (1997). PMID: 9100018 DOI: 10.1021/bi962658o.
Ting, Y.-T., Bhat, M.K., Wong, R. and Cheng, S.-Y.: Tissue-specific stabilization of the thyroid hormone β1 nuclear receptor by phosphorylation. Journal of Biological Chemistry, 272: 4129-4134, (1997). PMID: 9020124.
Bhat, M.K., McPhie, P., Ting, T.-Y., Zhu, X.-G. and Cheng, S.-Y.: The structure of the carboxy-terminal region of thyroid hormone nuclear receptor and its possible role in hormone dependent intermolecular interactions. Biochemistry, 34: 10591-10599, (1995). PMID: 7544615.
Bhat, M.K., McPhie, P. and Cheng, S.-Y.: Interaction of thyroid hormone nuclear receptor with antibody: Characterization of the thyroid hormone binding site. Biochemical and Biophysical Research Communications,210: 464-471, (1995). PMID: 7538760 DOI:10.1006/bbrc.1995.1683.
Bhat, M. K., Ashizawa, K. and Cheng, S.-Y.: Phosphorylation enhances the target gene sequence-dependent dimerization of thyroid hormone receptor with retinoid X receptor. Proceedings of National Academy of Science, USA. 91: 7927-7391, (1994). PMID: 8058736.
Cheng, S.-Y., Ransom, S. C., McPhie, P., Bhat, M. K., Mixson, A. J. and Weintraub, B. D.: Analysis of the binding of 3,3',5-Triiodo-L-thyronine and its analogs to mutant human β1 thyroid hormone receptors: a model of the hormone binding site. Biochemistry, 33: 4319-4326, (1994). PMID: 8155649.
Bhat, M. K., Parkison, C., McPhie, P., Liang, C. M. and Cheng, S.-Y.: Conformational changes of human thyroid hormone receptor induced by binding of 3, 3’, 5-Triiodo-L-Thyronine. Biochemical and Biophysical Research Communications, 195: 385-392, (1993). PMID: 8363616 DOI: 10.1006/bbrc.1993.2055.
Bhat, M. K., and Gowda, T. V.: Indian cobra (Naja naja naja) venom phospholipases A2- Isolation, purification, and characterization. Mysore University Science Journal,XXXII: 467-474, (1992).
Bhat, M. K. and Gowda, T. V.: Purification of a lethal phospholipase A2 (NN-IVb1-PLA2) from the Indian cobra (Naja naja naja) venom. Biochemistry International, 25: 1023-1034, (1991). PMID: 1810247.
Bhat, M. K., Kasturi, S., and Gowda, T. V.: Structure-function relationships among neurotoxic phospholipases: NN-X111-PLA2 from Indian cobra (Naja naja naja) and VRV-PL-V from Russell's viper (Vipera russelli) venoms. Toxicon, 29: 97-105, (1991). PMID: 2028476.
Bhat, M. K., Prasad, B. N., and Gowda, T. V. Purification and characterization of a neurotoxic phospholipase A2 from Indian cobra (Naja naja naja) venom. Toxicon, 29: 1345-1349, (1991). PMID: 1814010.
Bhat, M. K., and Gowda, T. V.: Purification and characterization of myotoxic phospholipase A2 from Indian cobra (Naja naja naja) venom. Toxicon, 27: 861-873, (1989). PMID: 2781585

 

Book Chapter

An invited article titled Strategy to develop new drugs Diabetes and Identification of new targets among the signaling path in the development of Diabetes by Maleppillil Vavachan Vijayakumar and Manoj Kumar Bhat, has been published in books entitled: Chronic Inflammatory Diseases and Nutraceuticals (Molecular Mechanism of Chronic Diseases, New Targets & Drugs and Basic Concept of Ayurveda). Edited by Yamini B. Tripathi, Pages 257-266, (2005).

 

Patents

  1. Method of preparing dialysed extract of fenugreek seeds which induces hypoglycemia, mediated, in part, via stimulation of insulin signaling pathway. Bhat, M.K. and Vijayakumar, M.V.,US Patent issue No. 8865237- dated: 21-10-12014
  2. Protein based product from fenugreek seeds that regulates dyslipidemia and obesity, and a process for the preparation thereof. Bhat, M.K. Pandey, V. and Vijayakumar, M.V., European Patent issue No. EP2323676- dated: 15-07-2015 (Germany and France); (PCT/IN2008/000877 dated: 30-09-2008, WO/2009/157013, dated: 30-12-09).

Awards and Honours

Recipient of Government of India National Merit Scholarship, 1983

Junior Research Fellowship, Indian Council of Medical research and University Grants Commission, 1986-87

Senior Research Fellowship, University Grants Commission, India, 1990

Fogarty International Research Fellow, 1993-1998, NCI, NIH, USA

Fellow, The National Academy of Sciences, India, 2011

Nominated for DST supported Khorana Program Technology Transfer Course 2012 under IUSSTF (University of Wisconsin 14/15 July-28/29 July 2012)

Member, Molecular Immunology Forum (India)

Indian Association for Cancer Research

Indian Society of Cell Biology

Dr. Bhat and his group's research related to fenugreek was featured in 'Wise Spice', a TV series broadcast by Vigyan Prasar and DST View Here


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Last updated On : 27 September 2022 06:15

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