Rakesh K. Tyagi

Professor
Special Centre for Molecular Medicine
Jawaharlal Nehru University
New Delhi-110067, INDIA
Tel.: 91-11-26738741, 26704559
Fax 91-11-26731781

E.mail: rktyagi@yahoo.com and
rkt2300@mail.jnu.ac.in

Education

Ph.D: Jawaharlal Nehru University, New Delhi
BSc (Hons) & MSc: Life Sciences, Visva Bharati University, Santiniketan
ICSE & ISC: St. Joseph’s Academy, Dehra Dun

Career

University Grants Commission (UGC), Government of India Research Fellowship (National Educational Test), 1986-1991.
Feinberg fellow of The Weizmann Institute of Science, Israel, 1993-1995. 
INSERM International Fellow, France, 1995-1997.
French Medical Research Fellow of ‘Foundation pour la Recherche Medicale’ 1997-1998.
University of Texas Health Science Center (UTHSCSA) Visiting Research Fellow 1998-2001.
Assistant Professor at the ‘Special Center for Molecular Medicine’, Jawaharlal Nehru University, New Delhi, India. 2001-2005.
Associate Professor at the ‘Special Center for Molecular Medicine’, Jawaharlal Nehru University, New Delhi, India. 2005 onwards.
Visiting Professor, Department of Biomedical Sciences, Bharathidasan University, Tiruchirappalli. 2006 onwards.
Chairperson, Centre for Molecular Medicine, Jawaharlal Nehru University, 2007-2009
Proctor, Jawaharlal Nehru University, Jan 2011 onwards

Membership

  • Member of the ‘Board of Studies in Endocrinology’, University of Madras, Chennai from 1.11.2010 to 31.10.2012
  • Editorial Board member: Journal of Endocrinology and Reproduction.
  • Ad hoc Reviewer for: Journal of Histochemistry and Cytochemistry, Biochimica Biophysica Acta, (Molecular Cell Research), FEBS Letters, BMC Cancer,  Indian Journal of Pharmacology etc.
  • Life Member of Indian Society of Cell Biology.>
  • Member of the PhD admission committees, National Institute of Immunology (NII), National Institute for Plant Genome Research (NCPGR) New Delhi
  • Life Member, Society of Reproduction Biology and Comparative Endocrinology, India
  • Life member, Society of Biological Chemists (SBC), India.

Awards & honors

  • Gold medal oration award by the Society of Reproductive Biology and Comparative Endocrinology (SRBCE) for significant contribution in the area of Molecular and Cellular Endocrinology.
  • Fellow of the National Academy of Sciences (NASI), Allahabad, 2010 onwards.
  • Awarded FRE (Fellowship in Reproduction and Endocrinology) by Society of Reproductive Biology and Comparative Endocrinology, 2009
  • Awarded French Medical Research Fellowship by ‘Foundation pour la Recherche Medicale’ 1997
  • Awarded INSERM (post verte) International Fellowship, France, 1995.
  • Awarded Feinberg fellowship of The Weizmann Institute of Science, Israel, 1993.
  • Recipient of S.R.V. Rao award to Young Scientist by Indian Society of Cell Biology, 1992.

Research interests

Nuclear Receptors in health and disease

The Nuclear Receptor super-family is a large group of ligand-activated transcription factors with 48 members presently identified in the human genome. Members of this family of receptors are involved in regulation of numerous physiological and patho-physiological processes and have great potential as targets for the treatment of diseases such as cancer, diabetes, coronary heart disease and asthma. Nuclear Receptors (NRs), that include steroid hormone receptors, are intra-cellular transcription factors that regulate gene expression in response to their cognate ligands. They function either as homodimers or as heterodimers with retnoid X receptor (RXR). NRs are attractive targets for drug discovery because their activities can be modulated by interacting ligands and have proved to be ‘drug-responsive’. However, some newly discovered members of this family of receptors remain incompletely understood, both in terms of physiological role and activating ligands. In brief, nuclear receptors represent enormous potential for drug discovery and are continuously being examined to unravel the mysteries underlying their mechanisms of actions. Towards better understanding of the functional significance of these transcription factors some of the comprehensive research projects have already been initiated in our laboratory. Presently, the role of androgen receptor mediated signaling in prostate cancer progression and the role of Pregnane & Xenobiotic Receptor in metabolism and clearance of endogenous metabolites and xenobiotics (including prescription drugs) is under investigation.

Research Projects

  1. Indian Council of Medical Research (ICMR), 2003-2006  (completed)
  2. Council for Scientific and Industrial Research (CSIR), 2003-2006  (completed)
  3. Bangalore Science Foundation, 2004-2006  (completed)
  4. Council for Scientific and Industrial Research (CSIR), 2006-2010 (completed)
  5. Department of Science and Technology (DST), 2007 onwards (in progress)
  6. Council for Scientific and Industrial Research (CSIR), April, 2010 onwards (in progress)

Pre-PhD course

Nuclear Receptors in Health and Disease (CMM 605)    3  credits
Nuclear Receptor superfamily: an introductory overview; structural and functional domains of nuclear receptors; ligand-mediated regulation of nuclear receptor function; nuclear receptor localization; receptor-ligand interactions and gene transcription regulation; co-activators and co-repressors; SRC/ p160, CBP/p300, histone (acetylase, deacetylase, methylase, demethylase), ATP dependent chromatin remodellers; receptor regulation by post-translational modifications e.g. phosphorylation, sumoylation, ubiquitination, acetylation, deacetylation, methylation etc.; nuclear receptors as drug targets; xenobiotic receptors and drug metabolism; screening and analysis of therapeutic ligands by high-throughput microscopy, co-transfection and transcriptional assays; steroid hormones and their receptors; molecular basis of endocrinopathies: endocrine-related cancers (prostate, breast, endometrial cancers); ligand-independent transcriptional activation of steroid hormone receptors; endocrine disruptors and selective steroid receptor modulators; current concepts and future challenges.

Research group

Dr. Monica Sharma (DST Woman Scientist)

PhD students

Aniruddha Sengupta (awarded 2003)
Mallampati Saradhi (awarded 14th January, 2008)
Jagannath Pal, 2002 (awarded 18th February, 2008)

Nagendra K. Chaturvedi, 2003 (awarded 27th January, 2009)
Subodh Kumar, 2003 (awarded 4th May, 2010)
Rachna Kaul, 2003 (awarded 25th May, 2010)

Sanjay Kumar, 2005 (awarded Dec. 28, 2010)
Sangeeta Kumari, 2006 (ongoing)
Priyanka, 2007 (ongoing)
Bharati Jaiswal, 2007 (ongoing)
Seema Negi, 2008 (ongoing)
Manjul Rana 2010 (ongoing)
Deepak Kumar 2010 (ongoing)

M.Sc. dissertation / summer training

Sanjay Kumar (completed 2003)
Kalpana Singh (completed 2003)
Harmeet Kaur (completed 2004)
Harish Kumar (completed 2005)
Neha Jain (completed 2005)
Vibhor K. Sharma (completed 2006)
Supriya Choudhary (completed 2006)
Neha Gujaria (completed June 2007)
Snigdha Debnath (completed June 2007)
Lalita Pryamvada (completed August 2009)
Debarati Mukherjee (completed March, 2010)
Ishara Datta (June-July, 2010)

Awards to Students

  • SANJAY KUMAR
    Winner of Prof. A. R. Rao Memorial Best Poster Award in the International Symposium on Cancer Chemoprevention and Translational Research, December 21, 2009, New Delhi, India. Poster title: Agonist-mediated docking of androgen receptor onto the mitotic chromatin platform discriminates intrinsic mode of action of prostate cancer drugs. Abstract *Code P.-38, pg 31.
  • Winner of Prof. N. J. Chinoy Award for the Best Poster in the International symposium on Endocrinology and Reproduction: Molecular Mechanisms to Molecular Medicine and the ‘28th Annual Meeting of the Society for Reproductive Biology and Comparative Endocrinology (SRBCE-2010)’ February 4-6, 2010, New Delhi, India. Poster title: Agonist-mediated docking of androgen receptor onto the mitotic chromatin platform discriminates intrinsic mode of action of prostate cancer drugs. Abstract *Code P.-79, pg 87.
  • SUBODH KUMAR
    Winner of the second best oral presentation award for “Inhibitory cross-talk between androgen receptor and xenobiotic receptor PXR defines an unexplored mechanism of action of antiandrogenic drugs” at the annual research festival Biosaprks-2009 conducted by School of life Sciences, Jawaharlal Nehru University.  6 & 7 March 2009.

    Recipient of the best oral presentation award for “Transcriptional cross-talk between androgen receptor and xenobiotic receptor PXR: an emerging perspective in prostate cancer therapy” at the international conference on "Novel updates in reproductive biology and comparative endocrinology ". University of Hyderabad, India. 19-21 January 2009
  • MALLAMPATI SARADHI and SANJAY KUMAR
    Won the best poster award on presenting a poster entitled ‘Docking of nuclear receptor onto the mitotic chromosomes: a mystery paving way for a future challenge’ during the 75th Annual meeting of the Society of Biological Chemists, held at Jawaharlal Nehru University, New Delhi, between 8-11th Dec’2006.

Total Publication: 31

Selected Publications

  1. Biswas A, Pasquel D, Tyagi RK, Mani S (2011) Acetylation of Pregnane X Receptor protein determines selective function independent of ligand activation. Biochem Biophys Res Commun. (in press)
  2. Amazit L, Roseau1 A, Ali-Khan1 J, Chauchereau A, Tyagi RK, Loosfelt H, Leclerc P, Lombes M, Guiochon-Mantel1 A (2011). Ligand-dependent Degradation of SRC-1 is Pivotal for Progesterone Receptor Transcriptional Activity. Molecular Endocrinology (in press)
  3. Chaturvedi NK, Kumar S, Negi S, Tyagi RK* (2010) Endocrine disruptors provoke differential modulatory responses on Androgen Receptor and Pregnane & Xenobiotic Receptor: potential implications in metabolic disorders. Molecular and Cellular Biochemistry 345:291-308
  4. Kumar S, Jaiswal B, Kumar S, Negi S and Tyagi RK (2010) Cross-talk between Androgen Receptor and Pregnane & Xenobiotic Receptor reveals existence of a novel modulatory action of antiandrogenic drugs. Biochemical Pharmacology 80: 964-976
  5. Pondugula SR, Brimer-Cline C, Wu J, Schuetz EG, Tyagi RK and Chen T (2009) A phosphomimetric mutation at threonine-57 abolishes transactivation activity and alters nuclear localization pattern of human pregnane X receptor. Drug Metabolism and Disposition 37:719-730
  6. Kumar S, Chaturvedi NK, Kumar S and Tyagi RK (2008) Agonist-mediated docking of androgen receptor onto the mitotic chromatin platform discriminates intrinsic mode of action of prostate cancer drugs. Biochimica et Biophysica Acta -Molecular Cell Research 1783:59-73
  7. Saradhi M, Kumar N, Reddy RC and Tyagi RK (2006) Pregnane and Xenobiotic Receptor (PXR): a promiscuous xensosensor with a role in human health and disease. Journal of Endocrinology and Reproduction 10: 1-12. Invited review.
  8. Kumar S, Saradhi M, Chaturvedi NK and Tyagi RK (2006) Intracellular localization and nucleocytoplasmic trafficking of steroid receptors: an overview. Molecular and Cellular Endocrinology 246: 147-156.
  9. Saradhi M, Sengupta A, Mukhopadhyay G and Tyagi RK (2005) Pregnane and Xenobiotic Receptor (PXR) resides predominantly in the nuclear compartment of the interphase cell and associates with the condensed chromosomes during mitosis. Biochimica et Biophysica Acta -Molecular Cell Research 1746: 85-94.
  10. Saradhi M, Krishna B, Mukhopadhyay G and Tyagi RK (2005) Purification of full-length human Pregnane and Xenobiotic Receptor: polyclonal antibody preparation for immunological characterization. Cell Research 15: 785-795.
  11. Kumar S, Chaturvedi NK, Nishi M, Kawata M and Tyagi RK (2004) Shuttling components of nuclear import machinery, involved in nuclear translocation of steroid receptors, exit nucleus via exportin-1 / CRM-1 independent pathway. Biochimica et Biophysica Acta -Molecular Cell Research 1691: 73-77.
  12. Sengupta A, Tyagi RK and Datta K (2004) Truncated variants of Hyaluronan Binding Protein 1 (HABP1) bind hyaluronan and induce identical morphological aberrations in COS-1 cells. Biochemical Journal 380:837-844
  13. Amazit L, Alj Y, Tyagi RK, Chauchereau A, Loosfelt H, Pichon C, Pantel J, Foulon-guinchard E, Leclerc P, Milgrom E and Guiochon-Mantel A (2003) Subcellular localization and mechanisms of nucleocytoplasmic trafficking of steroid receptor coactivator-1. Journal of Biological Chemistry 278: 32195-32203.
  14. Roy AK, Tyagi RK, Song CS, Lavrovsky Y. Ahn SC, Oh T and Chatterjee B (2001) Androgen receptor: structural domains and functional dynamics after ligand-receptor interaction. Annals of New York Academy of Sciences 949 : 44-57.
  15. Tyagi RK, Lavrovsky Y, Ahn CS, Song SC, Chatterjee B and Roy AK (2000) Dynamics of intracellular movement and nucleocytoplasmic recycling of the ligand-activated androgen receptor in living cells. Molecular Endocrinology 14 : 1162-1174 (Journal’s cover article).
  16. Tyagi RK, Amazit L, Lescop P, Milgrom E and Guiochon-Mantel A (1998) Mechanisms of progesterone receptor export from the nuclei: role of nuclear localization signal, nuclear export signal and Ran GTP. Molecular Endocrinology, 12 : 1684-1695.
  17. Tyagi RK, Azrad A, Degani H and Salomon Y, (1998) Stimulation of -melanocyteafructose 1,6 bisphosphate production in melanoma cells by  stimulating hormone: 31P/13C NMR and 32P labelling studies. European Journal of Biochemistry, 258 : 68-77.
  18. Tyagi RK, Azrad A, Degani H and Salomon Y, (1996) Simultaneous extraction of cellular lipids and water-soluble metabolites: evaluation by NMR spectroscopy. Magnetic Resonance in Medicine, 35 : 194-200.
  19. Tyagi RK, Babu BR and Datta K, (1993) Simultaneous determination of native and subunit molecular weights of proteins by pore limit electrophoresis and restricted use of sodium dodecyl sulphate. Electrophoresis, 14 : 826-828.

Patents

  1. Tyagi RK, Negi S, Kumari S, Saradhi M and Mukhopadhyay G (2010) Indian Patent filed through IPM cell at JNU, New Delhi. Indian Patent Application No. 464/DEL/2010 filed on 3.3.2010. PCT application number awaited.
  2. International patent number: WO0074485; Entitled: ‘Estrogen receptor site-specific ribozymes and uses thereof for estrogen dependent tumors’.
  3. Tyagi RK, Babu BR and Datta K, (1992) Indian Patent filed on 7th October 1992, Patent no.891/Dec. 1992.
  4. Sagar R, Tyagi RK and Datta K, (1994) Indian Patent filed on 17th June 1994, C.B.R. no. 9655.

TOP