Dr. Chauhan received his bachelor’s degree from Rajasthan University, Jaipur and Master’s from Guru Nanak Dev University, Amritsar, India. He joined the lab of Dr. JS Tyagi at All India Institute of Medical Sciences, New Delhi for his Ph.D. and his work was focused on transcriptional regulation in Mycobacterium tuberculosis.
After completion of his Ph.D. in 2009, he joined the laboratory of Dr. Douglas Boyd in the Department of Cancer Biology at the MD Anderson Cancer Center, Houston, US, for his first postdoctoral fellowship. His second postdoctoral fellowship was under the guidance of Dr. Vojo Deretic, one of the distinguished scientists in the field of autophagy at University of New Mexico (UNM), US.
He joined ILS in September 2015.
Please visit http://autophagylab.com for more details.
Autophagy is a fundamental catabolic process involved in cellular garbage degradation and recycling thus maintaining cellular metabolism and homeostasis. It is essential for cellular differentiation and embryonic development in mammals. In addition to these basic functions, autophagy plays several specialized roles in eukaryotic cells including cell-autonomous defense against intracellular pathogens and control of chronic inflammation. Not surprising, defects in autophagy have been linked to several diseases including cancer, neurodegeneration and cardiac pathologies. My major research interests are:
1. To understand the molecular mechanisms of autophagy regulation.
2. To understand the mechanisms by which autophagy accomplishes anti-microbial and anti-inflammatory functions.
Summary of Selected Publications:
Santosh Chauhan*, Suresh Kumar *, Ashish Jain*, Marisa Ponpuak*, Michal H. Mudd, Tomonori Kimura, Seong Won Choi, Ryan Peters, Michael Mandell, Terje Johansen, and Vojo Deretic. TRIMs and Galectins globally cooperate and TRIM16 and Galectin-3 codirect autophagy in endomembrane damage homeostasis. * Equal authorships. Developmental Cell. DOI: http://dx.doi.org/10.1016/j.devcel.2016.08.003
Selective autophagy performs an array of tasks to maintain intracellular homeostasis, sterility, and organellar and cellular functionality. The fidelity of these processes depends on precise target recognition and limited activation of the autophagy apparatus in a localized fashion. Here we describe cooperation in such processes between the TRIM family and Galectin family of proteins. TRIMs, which are E3 ubiquitin ligases, displayed propensity to associate with Galectins. One specific TRIM, TRIM16, interacted with Galectin-3 in a ULK1-dependent manner. TRIM16, through integration of Galectin- and ubiquitin-based processes, coordinated recognition of membrane damage with mobilization of the core autophagy regulators ATG16L1, ULK1, and Beclin 1 in response to damaged endomembranes. TRIM16 affected mTOR, interacted with TFEB, and influenced TFEB’s nuclear translocation. The cooperation between TRIM16 and Galectin-3 in targeting and activation of selective autophagy protects cells from lysosomal damage and Mycobacterium tuberculosis invasion.
Chauhan, S.*, Mandell, M. and Deretic, V.*. IRGM governs the core autophagy machinery to conduct antimicrobial defense. Volume 58, Issue 3, p507–521, 7 May, 2015 Molecular Cell. * Corresponding author.
coupling it to conventional innate immunity receptors. Exposure to microbial products or bacterial invasion increases IRGM expression, which leads to stabilization of AMPK. Specific protein-protein interactions and post-translational modifications such as ubiquitination of IRGM, lead to a co-assembly with IRGM of the key autophagy regulators ULK1 and BECN1 in their activated forms. IRGM physically interacts with two other CD risk factors, ATG16L1 and NOD2, placing these three principal players in CD within the same molecular complex. This explains how polymorphisms altering expression or function of any of the three factors individually can affect the same process – autophagy. Furthermore, IRGM’s interaction with NOD2, and additional pattern recognition receptors such as NOD1, RIG-I and select TLRs, transduces microbial signals to the core autophagy apparatus. This work solves the long-standing enigma of how IRGM controls autophagy.
Chauhan, S., Goodwin, J.G., Chauhan, S., Manyam, G., Wang, J., Kamat, A.M., and Boyd, D.D. (2013). ZKSCAN3 Is a Master Transcriptional Repressor of Autophagy. Molecular Cell. Apr 11, 2013 ;50(1):16-28.
Autophagy constitutes a major cell-protective mechanism that eliminates damaged components and maintains energy homeostasis via recycling nutrients under normal/stressed conditions. Although the core components of autophagy have been well studied, regulation of autophagy at the transcriptional level is poorly understood. In this paper, we establish ZKSCAN3, a zinc finger family DNA-binding protein, as a transcriptional repressor of autophagy. Silencing of ZKSCAN3 induced autophagy and increased lysosome biogenesis. Importantly, we show that ZKSCAN3 represses transcription of a large gene set (>60) integral to, or regulatory for, autophagy and lysosome biogenesis/function and that a subset of these genes, including Map1lC3b and Wipi2, represent direct targets. Interestingly, ZKSCAN3 and TFEB are oppositely regulated by starvation and in turn oppositely regulate lysosomal biogenesis and autophagy, suggesting that they act in conjunction. Altogether, our study uncovers an autophagy master switch regulating the expression of a transcriptional network of genes integral to autophagy and lysosome biogenesis/function.
This paper was Highlighted in Cancer Discovery (AACR) journal, February 28,
2013; doi:10.1158/2159-8290.CD-RW2013-046. In this highlight the ZKSCAN3 is described as switch, controlling the autophagy and lysosome biogenesis.
This paper was also Recommended by Faculty of 1000 (http://f1000.com/prime/717980675)
Santosh Chauhan*, Zahra Ahmed*, Steven B. Bradfute,….Vincent Piguet, and Vojo Deretic. Pharmaceutical screen identifies novel target processes for activation of autophagy with a broad translational potential. * Equal authorships. (Nat Commun. 2015 Oct 27;6:8620. doi: 10.1038/ncomms9620.)
Autophagy is a conserved homeostatic process active in all human cells and affecting a spectrum of diseases. In this study, we use a pharmaceutical screen (>3000 FDA approved drugs) to discover new mechanisms for activation of autophagy. We identify a subset of pharmaceuticals inducing autophagic flux with effects in diverse cellular systems modelling specific stages of several human diseases such as HIV transmission and hyperphosphorylated tau accumulation in Alzheimer’s disease. One drug, flubendazole, is a potent inducer of autophagy initiation and flux by affecting acetylated and dynamic microtubules in a reciprocal way. Disruption of dynamic microtubules by flubendazole results in mTOR deactivation and dissociation from lysosomes leading to Transcription Factor EB nuclear translocation and activation of autophagy. By inducing microtubule acetylation, flubendazole activates JNK1 leading to Bcl-2 phosphorylation, causing release of Beclin-1 from Bcl-2-Beclin-1 complexes for autophagy induction, thus uncovering a new approach to inducing autophagic flux that may be applicable in disease treatment.
Please visit http://autophagylab.weebly.com for more details.
Current Lab Members
1. Kshitish Kumar Rout -Lab Technician
2. Pradyumna Kumar Sahoo – Project Assistant
3. P. Srinath- Ph.D. Student
4. Kautilya Kumar Jena- Ph.D. Student
5. Parej Nath- PhD Student
6. Rashmi Patel- Project JRF
7. Arun Sankaradoss-Post-Doctoral Fellow
8. Subhash Mehto- National Post-Doctoral Fellow (SERB)
9. Kolapalli Srinivas- Post-Doctoral Fellow
10. Swati Chauhan- Scientist -WOS Scheme (affiliated to Dr. Rupesh Das lab)
The lab is currently open for the research scholars (at all levels, Postdocs, JRF, SRF..etc). The only criteria here is, hardworking and interest in the field of mainly Cell Biology, Autophagy, Innate immunity, Inflammation and also Epigenetic.
I will be more than happy to assist in writing and submitting the postdoctoral grant proposals (based on my lab interest) to the candidate scholars who have completed their Ph.D. or at later stages of Ph.D. completion. Following are the opportunities where I may be of help:
If interested, please send me an e-mail with your detailed CV. Please visit http://autophagylab.com for more details.
E-mail us at: firstname.lastname@example.org; email@example.com
Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar, India Pin 751023