Suman Kumar Dhar                             
 Professor
 Special Centre for Molecular Medicine
 Off. Phone: 011-26742572, 26704559
 Residence: 1442 Poorvanchal Complex, JNU, ND-67, #26742476
 E-mail:
skdhar@mail.jnu.ac.in , skdhar2002@yahoo.co.in
 
Web Address: http://www.jnu.ac.in/Faculty/sdhar

 

Area of Research

Bacterial/Parasite/Mammalian DNA Replication and cell cycle regulation 

Our lab in JNU is actively engaged in studying the unique characteristics of DNA replication and cell cycle regulation in two medically important pathogens, Plasmodium falciparum and Helicobacter pylori. Both these pathogens are extremely important although poorly understood from the basic biology point. Not a single effective vaccine is available for either of these pathogens. There are reports of drug resistant strains too. Our aim is to find the key regulators in DNA replication processes so that we can identify potential targets for therapy. The DNA replication process offers various important and interesting targets for new inhibitors development. Understanding the mechanism of initiation of DNA replication in P. falciparum and H. pylori will be useful in finding new targets for screening new antibiotics to eradicate these pathogens. We have already identified two such targets (PfGyrase for P. falciparum and HpDnaB helicase for H. pylori).

 

Education

 

INSTITUTION AND LOCATION

DEGREE
(if applicable)

YEAR(s)

FIELD OF STUDY

Burdwan University, West Bengal, India

B. Sc

1989

Chemistry

Kalyani University, West Bengal, India

 M. Sc.

1992

Biochemistry

Jawaharlal Nehru University, New Delhi, India

Ph.D.

1998

Molecular Biology

 

Career

1997-1998    Research Assistant, Dept. of Microbiology, University of Virginia, Charlottesville, USA

1998-2001    Post-Doctoral Fellow, Dept. Of Pathology, Harvard Medical School, Boston, USA     

2001-2005    Asstt. Professor, Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

2005-          Associate Professor, SCMM, JNU, New Delhi, India

2002-2003    Visiting Fellow, Dept. of Pathology, Harvard Medical School, Boston.

2003-2004    Visiting Fellow, Harvard School of Public Health, Boston, USA (summer)

2007            Visiting Fellow, Bernard Nocht Institute for Tropical Medicine, Hamburg, Germany

2008            Humboldt Fellow, Bernard Nocht Institute for Tropical Medicine, Hamburg, Germany

Research Projects

ONGOING

1. The Wellcome Trust, London                                            1/1/2005 to 31/12/2009
Functional Characterization of replication initiation proteins of Plasmodium falciparum

2. Indo-Swedish Link grant                                                   1/1/2007 to 31/12/2009
Replication restart mechanism in
Helicobacter pylori

3. Swarnajayanti Fellowship awarded by Department of Science and Technology                                                                                     1/5/2009 to 30/4/14
Control of DNA replication initiation and cell cycle regulation in two important human pathogens: Plasmodium falciparum and Helicobacter pylori.

Awards and honours

1992-1994     Junior Research Fellowship, Council of Scientific and Industrial Research, Govt. of India

1994-1997     Senior Research Fellowship, Council of Scientific and Industrial Research, Govt. of India

1997-1998     Training grant in emerging infectious diseases, National Institute of Health, USA

2000-2003     Post doctoral fellowship in breast cancer, Breast cancer research programme, Department of Army, USA

2002             International reviewer panel, Medical Science Monitor

2003             US Patent Application Approved by US Patent Office on "GEMININ AND ORC3N INHIBIT REPLICATION OF HERPESVIRUSES, PAMILOMAVIRUSES AND POLYOMAVIRUSES" BY DUTTA, A AND DHAR S.K. No. B0801.70253US00

2005-2009     Wellcome Trust Senior International Research Fellowship, Wellcome Trust, London

2007             Swarnajayanti Fellowship, Department of Science and Technology, Govt. of India

2008             Alexander Von Humboldt Fellowship awarded by Humboldt Foundation, Germany

 Ad-hoc reviewer:

Journal of Biological Chemistry, Molecular Microbiology, FEBS Journal, Medical Science Monitor and various Indian journals.

Membership

American Society for Microbiology
Elected member of Guha Research Conference (2007)

 

Publications

Papers published from JNU after setting up independent laboratory:

  1. Sharma A., Nitharwal RG., Singh B., Dar A., Dasgupta A and Dhar SK. (2009) Helicobacter pylori single-stranded DNA binding protein-functional characterization and modulation of H. pylori DnaB helicase activity. FEBS J. 276: 519-531

  2. Gupta, A., Mehra P. and Dhar SK. (2008). Plasmodium falciparum origin recognition complex subunit 5: functional characterization and role in DNA replication foci formation. Mol. Microbiol. 69: 646-65

  3. Prusty D., Mehra P., Srivastava S., Shivange AV., Gupta A., Roy N and Dhar SK. (2008) Nicotinamide inhibits Plasmodium falciparum Sir2 activity in vitro and parasite growth. FEMS Microbiol Lett. 282: 266-72.

  4. Nitharwal RG, Paul S, Soni RK, Sinha S, Prusthy D, Keshav T, RoyChoudhury N, Mukhopadhyay G, Chaudhury T, Gourinath S, and Dhar SK (2007) The domain structure of Helicobacter pylori DnaB helicase: The N-terminal domain can be dispensable for helicase activity whereas the extreme C-terminal region is essential for its function. Nucleic Acids Res. 35: 2861-74

  5. Dar MA, Sharma A, Mondal N and Dhar SK. (2007) Molecular cloning of apicoplast targeted Plasmodium falciparum DNA gyrase genes: unique intrinsic ATPase activity and ATP-independent dimerisation of PfGyrB subunit. Eukaryotic Cell. 6:398-412.

  6. Gupta A, Mehra P, Nitharwal R, Sharma A, Biswas AK and Dhar SK. (2006) Analogous expression pattern of Plasmodium falciparum replication initiation proteins PfMCM4 and PfORC1 during the asexual and sexual stages of intraerythrocytic developmental cycle. FEMS Microbiol. Lett. 261:12-8.

  7. Mehra P, Biswas AK, Gupta A, Gourinath S, Chitnis CE and Dhar SK. (2005) Expression and characterization of human malaria parasite Plasmodium falciparum origin recognition complex subunit 1. Biochem Biophys Res Commun. 337:955-66.

  8. Soni RK, Mehra P, Mukhopadhyay G and Dhar SK. (2005) Helicobacter pylori DnaB helicase can bypass E. coli DnaC function in vivo. Biochem J. 389(Pt 2):541-8

  9. Soni RK, Mehra P, Choudhury NR, Mukhopadhyay G, Dhar SK. (2003) Functional characterization of Helicobacter pylori DnaB helicase. Nucleic Acids Res. 31:6828-40.

  10. Dhar, S. K$., Soni R. K., Das, B. K. and Mukhopaddhyay, G. (2003) Molecular Mechanism of Action of Major Helicobacter pylori Virulence Factors. Molecular and Cellular Biochemistry 253:207-15 ($corresponding author)

  11. Jha S, Karnani N, Dhar SK, Mukhopadhayay K, Shukla S, Saini P, Mukhopadhayay G, Prasad R. (2003). Purification and characterization of the N-terminal nucleotide binding domain of an ABC drug transporter of Candida albicans: uncommon cysteine 193 of Walker A is critical for ATP hydrolysis. Biochemistry 42:10822-32.

  12. Dhar, S.K$., Mondal, N., Soni, R.K., and Mukhopaddhyay, G. (2002). A ~35 kDa polypeptide from baculovirus infected insect cells binds to yeast ACS like elements in the presence of ATP. BMC Biochemistry 2002, 3:23 ($corresponding author)

  13. Book Chapter:

  14. Wohlschlegel, J.A., Dutta, A. and Dhar, S.K. (2002). ORC and the Initiation of DNA Replication. Chemtracts: Biochemistry and Molecular Biology 15: 533-543.
  15. Sharma A and Dhar S. K. (2005) Helicobacter pylori: Diseases and Cure: a molecular approach in Microbes: Health and Environment edited by Prof. Ajit Varma. Publisher I. K. International. Delhi. India.

  16. Papers from post-doctoral research:

  17. Zhu W, Ukomadu C, Jha S, Senga T, Dhar SK, Wohlschlegel JA, Nutt LK, Kornbluth S, Dutta A. (2007) Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. Genes Dev. 21:2288-99.

  18. Dhar SK$, Saxena S, Yuan P, Senga T, Takeda D, Robinson H, Kornbluth S, Swaminathan K, Dutta A.   (2004) A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition. Mol Cell. 15:245-58. $Co-first author.

  19. Mondal N, Zhang Y, Jonsson Z, Dhar SK, Kannapiran M, Parvin JD. (2003) Elongation by RNA polymerase II on chromatin templates requires topoisomerase activity. Nucleic Acids Research 31(17):5016-24.

  20. Wohlschlegel, J.A., Dhar, S. K., Prokhorova, T. A., Dutta, A. and Walter, J. C. (2002) Xenopus Mcm10 binds to origins of DNA replication after Mcm2-7 and stimulates origin-binding of Cdc45. Mol. Cell 9(2):233-40

  21. Dhar, S.K., Yoshida, K., Machida, Y., Khaira, A., Chaudhuri, B., Wohlschlegel, J.A., Leffak, M., Yates, J. and Dutta, A. (2001) Replication from oriP of Epstein-Barr Virus requires human ORC and is inhibited by geminin. Cell 106(3), 287-96.

  22. Dhar, S.K., Delmolino, L. and Dutta A. (2001) Architecture of the human origin recognition complex. J. Biol. Chem. 276(31), 29067-71.

  23. Jonsson, Z.O, Dhar, S.K., Narlikar, G.J., Auty, R., Wagle, N., Pellman, D., Pratt, R.E., Kingston, R. and Dutta A. (2001) Rvb1p and Rvb2p are essential components of a chromatin remodeling complex that regulates transcription of over 5% of yeast genes. J. Biol. Chem. 276(19), 6279-88

  24. Wohlschlegel, J.A., Dwyer, B.T., Dhar, S.K., Cvetic, C., Walter, J.C., Dutta, A. (2000) Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Science 290(5500), 2309-12

  25. Thome, K.C., Dhar, S.K., Quintana, D.G., Delmolino, L., Shahsafaei, A. and Dutta A. (2000) Subsets of human ORC subunits are expressed in non-proliferating cells and associate with non-ORC proteins. J. Biol. Chem. 275(45), 35233-41

  26. Dhar, S.K. and Dutta, A. (2000). Identification and characterization of the human ORC6 homolog. J. Biol. Chem. 275(45), 34983-87

  27. Papers from Pre-doctoral research:

  28. Dhar, S.K., Vines, R.R., Bhattacharya, S. and Petri, W.A., Jr. (1998). Ribosomal DNA fragments enhance the stability of transfected DNA in Entamoeba histolytica. Jr. of Euk. Microbiol. 45(6), 656-660.

  29. Olvera, A., Olvera, F., Vines, R.R., Ricillas-Targa, F., Lizardi, P.M., Dhar, S.K., Bhattacharya, S., Petri, W.A. and Alejandro Alagon (1997) Stable transfection of Entamoeba histolytica trophozoites by lipofection. Arch. of Med. Res. 28, S49-51

  30. Dhar, S.K., Royhoudhury, N., Mittal, V., Bhattacharya, A. and Bhattacharya, S. (1996). Replication initiates at multiple random sites in the ribosomal DNA plasmid of the protozoan parasite Entamoeba histolytica. Mol. Cell. Biol. 16, 2314-2324.

  31. Dhar, S.K., Roychoudhury, N., Bhattacharya, A. and Bhattacharya, S. (1995). A multitude of circular DNAs exist in the nucleus of Entamoeba histolytica. Mol. Biochem. Parasitol., 70, 203-206.

  32. Sehgal D, Mittal V, Ramachandran S, Dhar SK, Bhattacharya A, Bhattacharya S. (1994) Nucleotide sequence organisation and analysis of the nuclear ribosomal DNA circle of the protozoan parasite Entamoeba histolytica. Mol Biochem Parasitol. 67:205-14.

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