RESEARCH AND TECHNOLOGY PROFILE
Computational biosciences research professional with 12+ years’ experience in academia and industry in the areas of high throughput data analysis and management for Agricultural Biotechnology and Cancer Research. Expertise spans across diverse computational data modeling and reporting to facilitate research analytical platforms. Independently managed customer centric product development using including Agile methodology. Key interests in data management and analytic areas towards business aligned value propositions.
Professional Achievements at DuPont Knowledge Center, Hyderabad, India
Roles and responsibilities held in areas of Computational Biology, HTP-Data framework/Management. Listed below are key projects/accomplishments.
• Designed and developed a novel framework to track types of experiments among diverse informatics resources within the organization and derive data lineage to enable analytics and decision making (Nominated for innovation award).
• Project lead for development of seed inventory Arabidopsis seed (Nominated for productivity award).
• Project lead for novel strategy for discovering regulatory elements based on transcriptomics for agronomic lead optimization (Notice of invention for the method has been filed).
• Designed and developed automated analytical pipeline for microarray data using ontologies with successful outcomes including reduced processing time and systematic representation for queried output.
• Data modeling and data integration of transcriptomic, sequence, phenotype data and gene annotations to perform integrated data analyses.
• Data migration from databases to data warehouse using ETL tools for enabling analytics.
Summary of research at Washington University School of Medicine
Comprehensive genomic analysis of Juvenile Pilocytic Astrocytomas (JPAs):
Pilocytic Astrocytomas (PAs) are grade I (WHO Grade I) tumors of the central nervous system. PAs are most common astrocytic (glial) tumors found in children. Juvenile Pilocytic Astrocytomas (JPAs) are believed to be a relatively homogenous subset of glial tumors; subtypes exist with different biological behaviors. There are severe limitations in the currently available therapies for JPA, necessitating novel approaches in their treatment, based on deeper/greater understanding of the molecular mechanisms at the genomic/genetic/protein level. To identify molecular targets for identification of an effective therapeutic agent for treating JPA, we pursued studies involving comprehensive and complementary high-throughput screening and analyses of DNA, RNA and proteins. We identified copy number gain on 7q34 locus containing the gene HIPK2, a homeobox-interacting protein kinase associated with malignancy. This gain was confirmed in an independent dataset using qPCR. Over expression of wild-type HIPK2, but not a kinase-inactive mutant, in a glioma cell line conferred a growth advantage in vitro suggesting role of HIPK2 in growth regulation. In summary, our study highlights the need to employ comprehensive and complementary technologies to identify subtle copy number changes that underlie the molecular pathogenesis of low grade tumors. Subsequently, I also identified mutations in BRAF and HIPK2 loci that predominate pilocytic astrocytoma and identified transcriptional regulatory networks specific to pilocytic astrocytoma.
Genomics of Acute Myeloid Leukemia (AML):
Acute Myeloid Leukemia, cancer of leucocytes (myeloid line) results in drop in red blood cells counts, platelets and white blood cells invariably leading to fatal outcome. The aim of this project is to comprehensively define the genetic changes using high-throughput sequencing, high-resolution DNA array-based comparative genomic hybridization, Single Nucleotide Polymorphism (SNP) genotyping and gene expression arrays to identify the mutations and the candidate genes that correlate with clinical outcomes and for therapeutic interventions.
o Identification of transcriptional regulatory networks specific to pilocytic astrocytoma. Hrishikesh Deshmukh, Jinsheng Yu, Jahangheer Shaik, Tobey J MacDonald, Arie Perry, Jacqueline E Payton, David H Gutmann, Mark A Watson, Rakesh Nagarajan, BMC Medical Genomics 07/2011; 4:57.
o High resolution array comparative genomic hybridization identifies copy number alterations in diffuse large B-cell lymphoma that predict response to immuno-chemotherapy. F Kreisel, S Kulkarni, R T Kerns, A Hassan, H Deshmukh, R Nagarajan, J L Frater, A Cashen, Cancer Genetics 03/2011; 204(3):129-37.
o Array-based comparative genomic hybridization identifies CDK4 and FOXM1 alterations as independent predictors of survival in malignant peripheral nerve sheath tumor. Jinsheng Yu, Hrishikesh Deshmukh, Jacqueline E Payton, Christopher Dunham, Bernd W Scheithauer, Tarik Tihan, Richard A Prayson, Abhijit Guha, Julia A Bridge, Rosalie E Ferner, Guy M Lindberg, Rebecca J Gutmann, Ryan J Emnett, Lorena Salavaggione, David H Gutmann, Rakesh Nagarajan, Mark A Watson, Arie Perry, Clinical Cancer Research 02/2011; 17(7):1924-34.
o In vitro transformation of primary human CD34+ cells by AML fusion oncogenes: early gene expression profiling reveals possible drug target in AML. Anmaar M Abdul-Nabi, Enas R Yassin, Nobish Varghese, Hrishikesh Deshmukh, Nabeel R Yaseen, PLoS ONE 01/2010; 5(8): e12464.
o Alterations of BRAF and HIPK2 loci predominate in sporadic pilocytic astrocytoma. J Yu, H Deshmukh, R J Gutmann, R J Emnett, F J Rodriguez, M A Watson, R Nagarajan, D H Gutmann, Neurology 09/2009; 73(19):1526-31.
o Acquired copy number alterations in adult acute myeloid leukemia genomes. Matthew J Walter, Jacqueline E Payton, Rhonda E Ries, William D Shannon, Hrishikesh Deshmukh, Yu Zhao, Jack Baty, Sharon Heath, Peter Westervelt, Mark A Watson, [……], Peggy S Eis, Rachel Maupin, Robert S Fulton, Michael McLellan, Richard K Wilson, Elaine R Mardis, Daniel C Link, Timothy A Graubert, John F DiPersio, Timothy J Ley, Proceedings of the National Academy of Sciences 08/2009;106(31):12950-5.
o A white-box approach to microarray probe response characterization: the BaFL pipeline. Kevin J Thompson, Hrishikesh Deshmukh, Jeffrey L Solka, Jennifer W Weller, BMC Bioinformatics 01/2009; 10:449.
o High-resolution, dual-platform aCGH analysis reveals frequent HIPK2 amplification and increased expression in pilocytic astrocytomas. H Deshmukh, T H Yeh, J Yu, M K Sharma, A Perry, J R Leonard, M A Watson, D H Gutmann, R Nagarajan, Oncogene 05/2008; 27(34):4745-51.
1) Ph.D. in Bioinformatics, May 2006, George Mason University, Fairfax, Virginia, USA
Ph.D. Dissertation Title: Modeling the physical parameters affecting measurements from microarrays
2) MS Biotechnology (Major: Biophysics), May 1999, University of Pune, India
MS Thesis Title: Evaluation of protein secondary structure prediction methods for accuracy
3)B.Sc. (Major: Microbiology, Chemistry, Zoology), 1997, Osmania University, Hyderabad, India
Agricultural Biotechnology and Cancer Research
R, S-Plus, SQL, Perl
Past & ongoing projects: