gototopgototop

Main Menu

Name:
Ashwani Kumar, Ph. D
Expertise:
Molecular Pathogenesis of Tuberculosis

Contact Address:

Ashwani Kumar Ph.D, 

Institute of Microbial Technology, 

Sector 39 A, Chandigarh, India 160036. 

Ph-0172-6665293, 0172-6665294 

Mob-9216530070 

E-mail-
ashwanik@imtech.res.in


Write-up of research and development interests/focus, past and present goals:

Objectives: To understand the basic physiology of mycobacteria in order to design improved diagnostics, better vaccines and novel drugs against tuberculosis.
Background and Significance Mycobacterium tuberculosis (Mtb) represents a major public health problem; killing ~2 million people along with 8 million new cases each year, in addition to 2 billion (1/3 of world’s population) latently infected people. The ability of Mtb to persist within humans for decades without any clinical symptoms and then to reactivate causing active disease is key to its success as a pathogen which ensure its continued maintenance, viability and efficient dissemination in humans. The lack of diagnostic tools, drugs, and therapeutic vaccines against latent infection of tuberculosis is major challenge in the control of disease. During last ten years I have exploited various multi-disciplinary approaches, new to the mycobacterial field to study the mechanisms utilized by Mtb to transit into latent state from actively growing state and believe that these findings will significantly contribute to the development of new vaccines, better diagnostics and novel drugs.
Ongoing lab projects
Based on above stated reasons my lab focus on host and bacterial mechanisms associated with Mtb dormancy and reactivation. I study the molecular mechanisms associated with Mtb latency such as
A. Mechanisms used by Mtb to sense hypoxia and NO.
It is established that presence of hypoxia and NO leads to induction of persistent mycobacteria that is resistant to a number of anti-tb drugs. However the mechanisms that are used by Mtb to sense and respond to these diatomic gases are not well understood. We have recently shown that hypoxia and NO are sensed through DosS and DosT two component proteins and that in addition to NO and hypoxia, CO can also induce the dormancy regulon. We are further characterizing heme based sensor SenX3 that plays an important role in sensing and responding to the concentration of diatomic gases hypoxia, NO and CO. Our work has demonstrated that SenX3 is an oxygen sensor that acts as an oxygen control replication switch. We have further shown that SenX3 controls the regrowth of Mtb upon exposure of hypoxic cultures to oxygen.

B. Role of Heme oxygenase -1 (HO-1) and its reaction products in pathogenesis of tuberculosis.
HO-1 catalyzes the oxidative catabolism of heme and leads to generation of molecular iron, biliverdin and carbon monoxide (CO). Lately it has been recognized that CO has similar properties to NO and act as a secondary messenger. The role of HO-1 in TB pathogenesis has not yet been investigated and represents a major gap in the TB field. Our lab is exploring the role of HO-1 in TB pathogenesis. We are more specifically exploring the role of HO-1 generated CO in cellular process as apoptosis/autophagy in addition to its role in modulation of Immune system.
C. Phenotypic switching in mycobacteria: Despite intensive treatment with multiple drugs for prolonged period of time, the recurrence of TB occurs in significant number of patients. However the underlying mechanisms behind this intrinsic drug resistance and persistence of the pathogen inside host for decades remain unknown.  Recent studies have unravelled mycobacterial capability to undergo phenotypic switching into the persister form, and into biofilm, providing plausible explanation of inherent drug resistance and prolonged persistence. However the molecular mechanism underlying such phenotypic switches remains unknown. Understanding these mechanisms will open new avenues of research for development of novel drugs, better diagnostic tools and more effective vaccines. Thus, a part of laboratory’s focus is to understand the molecular mechanism of phenotypic switching in mycobacteria.


Significant recognition: Awards, fellowships, international funding of distinction, technologies transferred/licensed etc.:

Significant Recognition: Editor in Microbial Cell (http://microbialcell.com/) 
 

Awards

Australia India Strategy Research Fund Awards for grand challenges sponsored through DST. 2013. Project Title "A Point of care diagnostic tool for tuberculosis".

UAB Centre for Free Radical Biology Travel Award for 14th Annual Society for Free Radical Biology and Medicine Meeting (SFRBM) in Washington, DC (2007).

First prize for research presentation at University of Alabam Birmingham Postdoctoral Research Day, Feb, 2008.

Excellence Award for postdoctoral research performed in the Department of Microbiology at University of Alabama Birmingham.

Keystone Symposia Scholarship for “Tuberculosis:  From Lab Research to Field Trials” held in Vancouver, British Columbia, Canada (2007).

Invited speaker at 108th General Meeting of American Society of
Microbiology in Boston, June 1-5 2008. Section 198/U. New perspectives on mechanisms of redox sensing by Mycobacterium tuberculosis. Sniffing
protective host signals through Fe-S and heme-based sensor proteins.


Selected list of Publications and Patents:

Selected Publications
 

Shabir Ahmad Bhat, Iram Khan Iqbal and Ashwani Kumar. Imaging the NADH:NAD+ homeostasis for understanding the metabolic response of Mycobacterium to physiologically relevant stresses. Frontiers in Cellular and Infection Microbiology. 6:145 doi: 10.3389/fcimb.2016.00145
 

Abhishek Trivedi, Parminder Singh Mavi, Deepak Bhatt, Ashwani Kumar. 2016. Thiol reductive stress induces
cellulose-anchored biofilm formation in Mycobacterium tuberculosis.
 Nat Commun. Apr 25;7:11392. doi: 10.1038/ncomms11392.

Singh N and Kumar A. 2014. Virulence factor SenX3 is the oxygen-controlled replication switch of Mycobacterium tuberculosis. Antioxidants and Redox Signalling. DOI: 10.1089/ars.2014.6020

Bhat SA, Singh N, Trivedi A, Kansal P, Gupta P, Kumar A. 2012. Mechanism of redox sensing in Mycobacterium tuberculosis. Free Radic Biol Med 53:1625-1641.

Trivedi A, Singh N, Bhat SA, Gupta P, Kumar A. 2012. Redox biology of tuberculosis pathogenesis. Adv Microb Physiol 60:263-324.

Kumar A, Farhana A, Guidry L, Saini V, Hondalus M, Steyn AJ. 2011. Redox homeostasis in mycobacteria: the key to tuberculosis control? Expert Rev Mol Med 13:e39.

Kumar A, Deshane JS, Crossman DK, Bolisetty S, Yan BS, Kramnik I, Agarwal A, Steyn AJ. 2008. Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium tuberculosis dormancy regulon. The Journal of biological chemistry 283:18032-18039.

Kumar A, Toledo JC, Patel RP, Lancaster JR, Jr., Steyn AJ. 2007. Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Proc Natl Acad Sci U S A 104:11568-11573.

Singh A, Mai D, Kumar A, Steyn AJ. 2006. Dissecting virulence pathways of Mycobacterium tuberculosis through protein–protein association.  Proceedings of the National Academy of Sciences of the United States of America 103:11346-11351.

Patents:

Adrie J. C. Steyn and Ashwani Kumar. Modulating latency and reactivation of Mycobacterium tuberculosis. Publication number-US8795978 B2; Application number US 12/666,008; PCT number;
PCT/US2008/067714 Publication date Aug 5, 2014

Follow me at goggle scholarSmile


Present group members:

The following graduate students and research fellows are working with me 
Abhishek Trivedi 
Nisha Singh 
Shabir Ahmed Bhatt 
Iram Khan 
Zeeshan Ahmed 
Parminder Singh Mavi 
Ajit Kumar Akela
Shikha Agarwal
Naveen Baid
Poushali Chakraborti
Naveen Thakur 
Sapna Bajeli 
Dr Hariom Kushwaha
Follow the lab at facebook (Ashwani Kumar Lab)

Past group members:

Pallavi Kansal
Geeta Pathania 
Pallavi vinayak
Nidhi Sharma
Asheema Vats   

This site is best viewed in Mozilla Firefox, Internet Explorer 8 and above at screen resolution of 1024 x 768 and above.