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Name:
Deepak Kumar Sharma
Expertise:
Protein Biophysics and Yeast Genetics

Contact Address:

Lab-301, GNRPC, IMTECH 
Ph. (Off): 172-6665478
Ph. (Lab): 172-6665479

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

Protein misfolding is the major cause of most of human diseases such as diabetes, cancer, cystic fibrosis and neurodegenerative diseases such as Alzheimer,Parkinson’s and prion diseases. Every cell has a network of proteins called chaperones that are evolved to refold misfolded  proteins back to their native state, and if repairing fails target them for degradation. However under various conditions, protein misfolding exceeds the preservative capacity of cells leading to protein aggregation affecting cellular viability. Thus approaches to further modulate action of chaperone machinery could provide common therapeutic targets for various protein misfolding diseases. Our lab employs both yeast genetics and single molecule approaches to understand why cellular machinery that is optimally evolved to maintain protein homeostasis fails to avert accumulation of misfolded proteins as well as proteinaceous masses known as amyloid. 

The major focus of our lab is to understand the complex interplay among chaperones and to explore whether chaperonome could be targeted to modulate balance between protein folding and degradation. We use biochemical as well as power of yeast genetic approaches to understand the molecular mechanism underlying how chaperones influence yeast prion (infectious proteins) formation and propagation. Yeast prions provide excellent models for understanding mammalian amyloid based diseases. One future direction is to explore Hsp70 as a therapeutic target to combat amyloid based diseases.
   

Other aspect of our future research would be to explore protein properties at single molecule level using Single Molecule Atomic Force Spectroscopy (AFS). Using AFS we are interested in understanding fundamental properties of amyloids such as mechanical rigidity as well as amyloid remodelling by purified chaperones. 




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

(1) Ramalingaswami Fellowship-2011, DBT, India
(2) The fellows Award for research Excellence-2009, NIH, USA.
(3) Nancy Nossal Fellowship award-2007, NIH, USA


Selected list of Publications and Patents:


Selected Publications from our lab:

 

1. Kumar N, Gaur D, Gupta A, Puri A, Sharma D,


(PLOS Genetics, 2015 Oct 16;11(10):e1005567, I.F. 8.0), Hsp90-associated
Immunophilin Homolog Cpr7 is Required for the Mitotic Stability of [URE3] Prion
in Saccharomyces cerevisiae

 

2. Kumar N, Gaur D, Masison D and Deepak Sharma,


The BAG Homology Domain of Snl1 Cures Yeast Prion [URE3] Through Regulation of
Hsp70 Chaperones (G3: Gene, Genomes, Genetics, 2014,4, 461-70)  

 

3. Jain R, Sharma D and Kumar R, 


Effects of Alcohols on the Stability and Low-Frequency Local Motions that
Control the Slow Changes in Structural Dynamics of Ferrocytochrome c (Journal
of Biochemistry, 2013, 154(4),341-54)

 

4. Singh N, Haldar S, Horback K, Wong J, Sharma D, Bessera A, Suda S,Mukhopadhyay C, Singh A, Dev S,


Brain Iron Homeostasis: From Molecular Mechanisms to Clinical Significance and
Therapeutic Opportunities, (Antioxid Redox Signal, 2013, 20(8), 1324-63)

 

5. Kumar S, Sharma D, Kumar R

 

Effect of Urea and Alkylureas on the Stability
and Structural Fluctuation of the M80-containing 
 W-loop of Horse Cytochrome c, (BBA-Proteins and
Proteomics, 2014, 1844(3),641-55).
 



Selected Previous Publications:

 

1. Sharma D and Masison DC.


Single methyl group determines prion propagation and protein degradation
activities of yeast heat shock protein (Hsp)-70 chaperones Ssa1p and Ssa2p, (PNAS
2011, 108(33): 13665-70).

 

2. Sharma D, Feng G, Khor D, Genchev G, Lu H, Li H,


Stabilization provided by neighboring strands is critical for the mechanical
stability of proteins, (Biophysical Journal, 2008, 95(8): 3935-42).

 

3. Sharma D, Perisic O, Peng Q, Cao Y, Lam C, Lu H, Li H,


Single-molecule force spectroscopy reveals a mechanically stable protein fold
and the rational tuning of its mechanical stability. (PNAS, 2007, 104(22):
9278-83).

 

4. Sharma D, Cao Y, Li H,


Engineering proteins with novel mechanical properties by recombination of
protein fragments. Angew Chem Int Ed Engl.,(2006, 45(34): 5633-8).



Present group members:


1.   Muddassir – Research Associate
2.   Surjeet – Technical Assistant
3.   Navinder Kumar– Ph.D. Student
4.   Deepika Gaur – Ph.D. Student
5.   Arpit Gupta – Ph.D. Student
6.   Prashant Singh - Ph. D. Student
7.   Priyanka – Ph. D. Student
8.   Anuradhika Puri – Junior Research Fellow      
9.   Vibhuti Nandel – Junior Research Fellow      
10. Jyoti  - Junior Research Fellow
11. Isha Gouri – Project Assistant 











Past group members:


1. Md. Suhail

2. Gursharan kaur

3. Surabhi Sonam
4. Richa Pandey
5. Monika

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