Research Groups

Molecular Medicine: Cellular Immunology

Research Interests and Description

Group Leader: Dhiraj Kumar, PhD

Group Members

Research Interests

Phagocyte cell-biology, innate immune responses to Mycobacterium tuberculosis or HIV infections, High-throughput biology and computational biology.

Description of Research

The major research area of the lab is to understand the innate defense mechanisms in humans in response to pathogenic infections like Mycobacterium tuberculosis (Mtb) or HIV. One of the major cellular processes being investigated in this context is regulation of autophagy. Autophagy is cellular homeostatic mechanism, which has also been implicated in the control of intracellular infections. The Group has recently established an exciting concept of selectivity in autophagy,  showing uncoupling between the homeostatic arm and anti-mycobacterial arm of autophagy within the cell. To further understand the role of autophagy in the innate defense mechanism we have explored the relationship between autophagy, inflammation and cellular metabolism. These processes are intricately interlinked and this realisation has allowed us to envisage a much more significant role of innate defense mechanisms in determining the consequences of infection in the human population. We are using established models like tuberculosis infections, classical activation and inflammatory bowel diseases as models to understand this critical regulatory mechanism. We also believe that the role of innate defense mechanism in the context of HIV infections has not been explored greatly. We are therefore applying our understanding of cell autonomous defense mechanism to address this specific question in case of HIV infection as well as HIV-TB co-infections. In addition to the classical innate defense mechanisms we are also exploring unconventional niches for intracellular pathogens through cell biology approaches. To achieve these objectives we employ high-end confocal microscopy in addition to molecular biology, biochemistry and cell biology tools.
The Group is also interested in understanding macrophage responses to various stimuli including infections at the transcriptional level. In the past, using microarray analysis we successfully identified some key regulators of intracellular survival of Mtb. Key leads obtained from these studies are currently being tested in the animal models of tuberculosis as adjunct therapy. Moreover, we recently showed extensive alteration in the host RNA splicing pattern during mycobacterial infection, which has led to the development of a major new area of research in the group. Further, we have developed in-house analytical tools to understand the complex nature of transcriptional reprogramming in the macrophages in response to Mtb infections using next-generation RNA-seq approach. 

Recent Publications

Vashi, N., Andrabi, S.B., Ghanwat, S., Suar, M., Kumar, D. 2017. Ca2+-dependent Focal Exocytosis of Golgi-derived Vesicles Helps Phagocytic Uptake in Macrophages J Biol Chem 292, 5144-5165 PubMed link

Kalam, H., Fontana, M.F., Kumar, D. 2017. Alternate splicing of transcripts shape macrophage response to Mycobacterium tuberculosis infection. PLoS Pathon 13, e1006236 PubMed link

Matta, S.K., Kumar, D. 2016. Hypoxia and classical activation limits Mycobacterium tuberculosis survival by Akt-dependent glycolytic shift in macrophages. Cell Death Discov 30, 2 PubMed link

Klionsky, D.J., Abdelmohsen, K., Abe, A., Abedin, M.J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C.M., Adams, P.D., Adeli, K., et al. 2016. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12, 1-222 PubMed link

Chandra, P., Rajmani, R.S., Verma, G., Bhavesh, N.S., Kumar, D. 2016. Targeting Drug-Sensitive and-Resistant Strains of Mycobacterium tuberculosis by Inhibition of Src Family Kinases Lowers Disease Burden and Pathology mSphere 1, e00043-00015 PubMed link

Chandra, P., Kumar, D. 2016. Selective autophagy gets more selective: Uncoupling of autophagy flux and xenophagy flux in Mycobacterium tuberculosis-infected macrophages. Autophagy 12, 608-609 PubMed link

ICGEB New Delhi

ICGEB Campus
Aruna Asaf Ali Marg
110 067 New Delhi
INDIA
Tel: +91-11-26741358/1007
Fax: +91-11-26742316
icgebicgeb.res.in

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