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Institute of Molecular Medicine
254 Okhla Industrial Estate, Phase III
New Delhi: 110020, India
Phone No: 011-41028710
Fax. No: 011-41028709
Email: sudeshnak@immindia.org
1999 Ph.D (Life Sciences) Indian Institute of Chemical Biology, India
1993 M.Sc (Biophysics and Molecular Biology) Calcutta University, India
Nov, 2007 - Present: Team Lead; Institute of Molecular Medicine, New Delhi, India.
2003 - 2007: Staff Fellow, National Cancer Institute, National Institutes of Health. USA
1999 - 2003: Visiting Fellow, National Cancer Institute, National Institutes of Health. USA.
2005-2006 Howard Hughes Institute Award of Excellence for NIH Internship program
2003 Technology Transfer Award of National Cancer Institute.
1993-1998 National research fellowship from CSIR
Gene-cassette for enhancement of protein production. PCT/US2005/017001, WO 2005/11622
Sudeshna Kar and Sankar Adhya
Research Support Member: Mr. Sudhansu Sudan (Research Trainee)
Engineering and development of tumor-killing bacterium from benign commensals.
We have constructed an invasive form of the non-pathogenic E.coli K-12 which is highly cytolytic towards human glioblastoma and breast cancer cells. We are in the process of developing this bacterium to target refractory and non-responsive human cancers with minimal toxic side effects. Using cell culture, biochemical and animal model techniques, we are also trying to identify of new genes/signaling pathways involved in killing of malignant cells, including concurrent triggering of multiple pathways of cell death as well as discover global signature features for use as diagnostic and drug-response biomarkers in glioblastoma.
Conversion of non-virulent resident microbes into opportunistic pathogens in the absence of any genetic changes.
Most studies on the genesis and evolution of pathogenic bacteria conclude that virulent strains emerge from avirulent ones by acquiring new virulence factors through horizontal transfer of accessory DNA. However, there are increasing evidences that a large number of commensal bacteria residing inside humans can cause significant morbidity and mortality even in the absence of any genomic changes. Using a in-vitro locked-in mutant of commensal E.coli as positive control, we are studying the molecular mechanisms and cellular signatures in bacteria undergoing commensal-pathogen transition, genetic and physiological host factors which promote this change in microbial virulence state and small molecule inhibitors of bacterial factors responsible for genesis of opportunistic pathogens.
Developing Neuroprotective Agents for Neurodegenerative Disease.
We have identified a hydrophobic bacterial protein that shows promising results as a neuroprotective agent in preventing neuronal cell death under stressful conditions. Initial results show that this protein interacts with HDAC and change the HDAC/HAT ratio in moribund neurons. We are in the process of delineating and understanding the cellular pathways and molecular mechanisms by which this protein prevent neuronal cell death, with the ultimate objective of using this molecule for the treatment of neurodegenerative diseases.
Building a microbial chemical factory.
We are trying to metabolically engineer the photosynthetic bacteria, Rhodopseudomonas palustris, to utilize methane as a sole carbon source for the production of usable hydrogen, plant monoterpenoids (geraniol and citronellol) and vitamins D, E and K.
Kar, S., E. J. Choi, F. Guo, E. K. Dimitriadis., S. Kotova and S. Adhya. 2006. Right-handed DNA wrapping by an octameric form of histone-like protein HU modulates cellular transcription. Journal of Biological Chemistry 281(52): 40144-53.
Kar, S., R. Edgar and S. Adhya. 2005. Nucleoid remodeling by an altered HU protein: reorganization of the transcription program. Proceedings of the National Academy of Science U S A 102(45):16397-402.
Rao, S., S. Hu, L. Mchugh, L. Lueders, K. Henry, Q. Zhao, R. A. Fekete, S. Kar, S. Adhya and D. H. Hamer. 2005. Toward a live microbial microbicide for HIV: commensal bacteria secreting an HIV fusion inhibitor peptide. National Academy of Science U S A 102(34):11993-8.
Roy, S., E. Dimitriadis, S. Kar, M. Miller, S. Adhya and S.Gal. 2005. Repressor-Operator-HU Ternary Complex: Pathway of Repressosome Formation. Biochemistry 44(14):5373-80.
Adhya, S., F. Guo and S. Kar. 2005. HU, nucleoid structure and transcription profile. Journal of Biomolecular Structure and Dynamics (6).
Kar S and S. Adhya. 2001. Recruitment of HU by piggyback: a special role GalR in repressosome assembly. Genes and Development. 15(17): 2273-81.
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