Office Phone: (+91-22) 2740 5112 2740 5000
One Key Research Area: Proteomics, Structure Biology and Bioinformatics
Special interests: Structural aspects of BRCA1/2 and interacting partners, MAP Kinase pathways, Proteomics of Head and neck squamous cell carcinoma
About us: A mission statement of the Laboratory in a line if any: Translational research in life sciences
Brief information on the activities of the Laboratory :
Multi-disciplinary approaches like biophysical techniques, macromolecular crystallography, structural biology and bioinformatics tools are being used in my lab to visualize the atomic association of cancer susceptibility Genes and Proteins for translational research. Protein-Protein, Protein-Small molecule interactions important at the bioactive core at the complex interface will be targeted for translational research. At present my lab has state of art facility for structure biology. Proteomics of metastasis to find novel diagnostic biomarker has also initiated.
Project: 1 Structural & Functional Approaches to evaluate BRCA1/2: A Gene for Genetic Counseling, (2) A Target for Drug-Discovery:
There are several BRCA1/2 cellular binding partners that regulate protein function using protein-protein interactions at the active site of complex molecule. My group is aiming to characterize each complex associated to BRCA1/2 . We have cloned several functional domains of BRCA1 and its binding partners like CsTF, BRCA2, BARD1, MDC1, BAP1. Few domains has already been purified. The focus is also to characterized pathogenicity of mutants discovered in Indian families and also from Breast Cancer Information Core (BIC). Pathogenicity of mutants will be characterized using multi model based approach of in-vitro, bioinformatics, biophysics, and structure biology.
Project: 2 Role of h-RAP80-ABRAXAS-BRCA1 Complex in the DNA damage repair: Structural Investigations to reveal molecular complexity.
The Receptor Associated Protein -80 (RAP80) comprises several functionally important domains and interacts with BRCA1 through an intermediate binding partner. One of my Ph. D students Mr. Vikrant is working full time on this project. In this paper we have communicated two research papers. First paper entitled “Characterization of the MERIT40 for its DNA repair function” and second one “Structural and Functional Implication of RAP80 Δ81Glu Mutation” have been communicated. Vikrant has competed purification part and crystallization of different purified proteins are under process. Proteomics for reported pathogenic mutants has been analyzed. Protein-protein interactions using ITC, BIACORE has been reported.
Project: 3 Structural basis of MAPK in association with Ribosomal S6 Kinases
The aim for this project is to study the structural basis of c –Raf downstream kinase like MEK1/2, ERK1/2 and RSK1/2/3/4. Structural studies of MAPK family are very important because the mutations in any of the genes in this pathway are responsible for several human cancer. Mr. Bhanu has cloned and purified several functional domains of ERK1/2 and SRKs. Crystallization for purified protein is under process. We have communicated one paper entitled “Specific Conserved Residues at the RAF1- MEK1- ERK2 - RSKs Binding Interfaces that Regulate Transcriptional Machinery”. We are characterizing the protein-protein interactions to find how few amino acids located at the MAPK interface regulate the transactivation function.
Project: 4 An exploratory study of a set of predictive and prognostic protein biomarkers in Head and neck squamous cell carcinoma treated with radiotherapy.
In this project we are looking for predictive and prognostic protein biomarkers. The main objective of this project is to isolate, purify and understand predictive potential of a set of proteins which are known to be good prognostic indicators. Based on available published data, we have found cytokine serum levels in head and neck cancer patients could co-relate with patients response to treatment. We are planning to study expression levels of inflammatory cytokines, angiogenic markers and cytokeratins at different time points during radiotherapy. We have identified a group of proteins playing role in inflammatory processes, angiogenesis and few cytokeratin’s; as these proteins are a very important part of tumor microenvironment and their altered expression profile during course of the treatment may reflect changes in tumor development and patient’s response to treatment.
Dilip Badgujar Lumbini Yadav Vikrant Bhanu Prakash Rajan Kumar Quadir Siddiqui Priyanka Arora Mahamaya Dhwani Thakkar
Jaspreet Kaur Osan Elavarasi Anbalagan Payal Gala Sneha Lalwani Prachi Khare Poulami Chatterjee Nishita Bhembre Hafiza M. Mahadik Gargi Indurkar, Ranjana S. Pathak,. Poornima Rao, Khushboo Rathore; Priyanka Rao, Medha Sonavane, Pallavi Nakhwa Meeti Soni Gargi Indurkar Amruta N. Patil Deepali R. Patil Priyam Saxena Supriya Landge Namrata Gadag Dr.Anamika Pandey , Rita Verma, Ansari Mubashshera AB Rasheed Shivani Shah Rohan Patil, Suranjana Das Shanoli Ghosh Rashmi Yadav Omkar Indulkar Akshay Walia, Harshal Mehta, Ishrat S. Siddiqui Aman S. Patel Jyoti R. Tripathi. Lipika Patel Darshan Chavan Priya Abhishek Bhavana Dwivedi Bhaswati Banerjee B. Vignesh Kumar Rohan S. Patil, Tariq M. Vakil, Piyush G. Malve, Sanket R. Awate
Opportunities: I always welcome project student for six month to a year, but once can take only five.
1. S.Kumar, L.Jena, S.Daf, K. Mohod, P. Goyal, Ashok K Varma. hpvPDB: An Online Proteome Reserve for Human Papillomavirus. Genomics Inform. Dec;11(4):289-91 (2013).
2. Dilip C. Badgujar, Ulka Sawant,Vikrant, Lumbini Yadav, M. V. Hosur and Ashok K. Varma, Preliminary crystallographic studies of BRCA1 BRCT–ABRAXAS complex, Acta Cryst. F69, 1401–1404, (2013).
3. R.C. Chandarana, Vikrant, Ashok K Varma, A. Saran A, E.C. Coutinho, J. D'souza, Over-expression, purification and isotopic labeling of a tag-less human glucose-dependent insulinotropic polypeptide (hGIP), 3 Biotech 13205-013-0181,(2013)
4. Vikrant, Disha Shah, Pallavi Nakhwa, Dilip C Badgujar, Khushboo K.S Rathore, Ashok K Varma, Structural and Functional Characterization of MERIT40 for its DNA Repair Function J Biomol Struct Dyn. 2013,
5. Vikrant, Rajan Kumar, Lumbini R Yadav, Pallavi Nakhwa, Sanjeev K Waghmare, Ashok K Varma Structural and Functional Implication of RAP80 Δ81Glu Mutation, PLoS ONE 8(9):e72707 (2013)
6. Ajit K. Sharma. Abhilasha Mansukh, Ashok K Varma, Nikhil Gadewal and Sanjay Gupta, Molecular Modeling of Differentially Phosphorylated Serine 10 and Acetylated lysine 9/14 of Histone H3 Regulates their Interactions with 14-3-3ζ, MSK1, and MKP1, , Bioinformatics and Biology Insights, 7 1–18 (2013)
7. Gadewal, N, Varma A.K.: Targeting Pim-1 Kinase for Potential Drug-Development Int. J. Computational Biology and Drug Design, Vol. 5(2), 137, (2012).
8. Dilip C Badgujar, Ulka Sawant, Hafiza Mahadik, Nikhil Gadewal and Ashok K Varma, Pathogenicity of Mutations Discovered in BRCA1 BRCT Domains is Characterized by Destabilizing the Hydrophobic Interactions, J Cancer Sci Ther, Volume 4(11) 386-393 (2012).
9. Patil R, Das S, Stanley A, Yadav L, Sudhakar A, Varma AK: Optimized Hydrophobic Interactions and Hydrogen Bonding at the Target-Ligand Interface Leads the Pathways of Drug-Designing. PLoS ONE, 5(8); e12029, (2010).
10. Khan Z, Khan N, Varma AK, Tiwari RP, Mouhamad S, Prasad GB, Bisen PS: Oxaliplatin-Mediated Inhibition of Survivin Increases Sensitivity of Head and Neck Squamous Cell Carcinoma Cell Lines to Paclitaxel. Curr Cancer Drug Targets. 10(7): 660-669, (2010).
Links: Applications / online sources developed by the Department
Awards / Honors:
Member: Life member - Indian Crystallographic Association, Indian Association for Cancer Research, - Indian Biophysical Society, Society of Biological Chemists
Any other: Webpage: http://www.actrec.gov.in/pi-webpages/AshokVarma/varma-index.htm