Dipankar Nandi

Professor

Ph.D.

Dept. of Molecular & Cell Biology and Graduate Group in Endocrinology, University of California-Berkeley, U.S.A. 1991

Postdoctoral Research

Dept. of Molecular & Cell Biology and Division of Immunology, University of California-Berkeley, U.S.A. 1991-1992
Dept. of Microbiology and Immunology, Virginia Commonwealth University, U.S.A. 1992-1993
Dept. of Molecular Genetics, University of Cincinnati, U.S.A. 1993-1997
Tel: 91-80-22933051
Email: nandi@biochem.iisc.ernet.in


 Research

  • Studying novel microbial genes during stress and infection
  • Understanding the host encoded immune responses

The overall objective our laboratory is to understand biological responses to different stimuli. For this purpose, we utilize microbial systems as well as the host encoded immune system. Over the years, we have established a diverse array of models and expertise that help us to understand the roles of various genes and signals in modulating microbial and host encoded responses. Broadly, the twin areas of interests of our laboratory are:

  • Studying novel microbial genes during stress and infection
  • Understanding the host encoded immune responses

A) Studying novel microbial genes during stress and infection
Cytosolic protein degradation is important for regulation of several cellular processes and can be divided into two parts: ATP-dependent and ATP-independent. Giant enzymes known as proteasomes are required for the majority of cytosolic protein degradation in eukaryotes. Several years back, our laboratory identified Peptidase N (PepN), the sole M1 family member in E. coli and S. typhimurium to be a major aminopeptidase. Over the years, we have studied the roles of this enzyme during stress and infection, using a combination of genetics, microbiology, biochemistry and immunology.

Some aspects of structure-functional relationship of PepN with respect to its biochemistry and function and roles of other proteases and peptidases during stress responses are on going. However, the emphasis now will be on functional roles of novel genes during stress responses and infections.

B) Understanding the host encoded immune responses
There are two subordinate areas under this heading.
T cell biology:
T cells are required for cellular immunity and play key roles during the adaptive immune response. Host immunity is greatly compromised if CD4+ T cells are absent or lowered, as seen in AIDS patients. We have established a primary CD4+ T cell culture system and can modulate their activation (low versus high) using different stimuli, e.g. anti-CD3 stimulation, combinations of a phorbol ester and different amounts of Ionomycin etc. This is, in essence, known as the strength of signal. Efforts are geared towards studying the mechanistic aspects, especially the roles of different species of free radicals, in modulating T cell responses. In addition, we are studying the roles of small molecules in modulating CD4+ T cell activation and survival and attempting to understand their mechanism/s of action. As far as in vivo T cell responses are concerned, we have shown the role of heat killed Mycobacterium indicus prannii (an adjuvant) in inducing anti-tumor T cells to reduce tumor growth.

T cell differentiate in the thymus and the loss of thymocytes resulting in thymic atrophy, is known to occur during many infections. We have standardized a model of thymic atrophy using a model of oral infection by Salmonella enterica serovar Typhimurium, an intracellular pathogen. We are studying multiple aspects during this process, including, expression of cell surface markers, death markers, the roles of different signalling pathways etc. The mechanistic insights uncovered in this study may be important in designing effective strategies to reduce thymic atrophy during infections. This aspect is important as enhancement of thymic output will increase the numbers and diversity of thymic T cell emigrants in the periphery to boost host responses during infections.

Inflammatory and Interferon-gamma modulated responses:
Inflammation is important for host defense; however, too much of it is harmful as it can cause immunopathology, resulting in harm to the host. A key cytokine involved is Interferon-gamma (IFN-gamma) which is produced mainly by activated T cells and NK cells. Humans lacking IFN-gamma or its receptors are extremely susceptible to infections by intracellular pathogens, e.g. Mycobacterium tuberculosis, S. typhimurium etc. Our laboratory has been studying the roles of IFN-gamma and shown the roles of oxidative and nitrosative stress in modulating the expression of IFN-gamma-regulated genes. We have now extended this study to macrophages and are attempting to identify novel IFN-gamma regulated genes and responses that are modulated by Nos2. Current efforts are also directed towards understanding the expression and roles of novel IFN-gamma-regulated genes in cell growth suppression and modulation of intracellular growth of Salmonella enterica serovar Typhimurium.

Overall, our laboratory works at the interface of microbiology and immunology.

 Lab Members


 Key Publications

  • Deobagkar-Lele M, Victor ES, Nandi D. c-Jun NH2 -terminal kinase is a critical node in the death of CD4+CD8+ thymocytes during Salmonella enterica serovar Typhimurium infection. Eur J Immunol. (2014) 44:137-49. PubMed
  • Chandrasekar B, Deobagkar-Lele M, Victor ES, Nandi D. Regulation of chemokines, CCL3 and CCL4, by interferon-gamma and nitric oxide synthase 2 in mouse macrophages and during Salmonella enterica serovar typhimurium infection. J Infect Dis. (2013) 207:1556-68. PubMed
  • Deobagkar-Lele M, Chacko SK, Victor ES, Kadthur JC, Nandi D. Interferon-γ- and glucocorticoid-mediated pathways synergize to enhance death of CD4+ CD8+ thymocytes during Salmonella enterica serovar Typhimurium infection. Immunology. (2013) 138:307-21. PubMed
  • Bhosale M, Kumar A, Das M, Bhaskarla C, Agarwal V, Nandi D. Catalytic activity of Peptidase N is required for adaptation of Escherichia coli to nutritional downshift and high temperature stress. Microbiol Res. (2013) 168:56-64. PubMed
  • Rakshit S, Ponnusamy M, Papanna S, Saha B, Ahmed A, Nandi D. Immunotherapeutic efficacy of Mycobacterium indicus pranii in eliciting anti-tumor T cell responses: critical roles of IFNγ. Int J Cancer. (2012) 130:865-75. PubMed
  • Bhosale M, Pande S, Kumar A, Kairamkonda S, Nandi D. Characterization of two M17 family members in Escherichia coli, Peptidase A and Peptidase B. Biochem Biophys Res Commun. (2010) 395:76-81. PubMed