My research career began at the Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai, India, as a graduate student working on understanding the genetic basis of congenital heart diseases using epidemiological and cytogenetic approaches. Following my graduate school training, I joined University of Vermont, Burlington, VT as a postdoctoral research associate where I isolated and characterized human smooth muscle myosin heavy chain isoforms and studied their role as molecular markers in vascular development and atherosclerosis. After a brief period, I returned to India to establish a diagnostic genetics laboratory in a leading specialty Hospital that provided diagnostic services based on constitutional karyotype analysis. I continued my postdoctoral training at the Miami Children’s Hospital, Miami, FL in 1993 where I was involved in the characterization and estimation of population frequency of mutations in human aspartoacylase gene associated with Canavan disease. My training at University of Vermont and Miami Children’s Hospital allowed me to gain skills in molecular biology techniques and their application in basic research. In 1996 I had the opportunity to join the laboratory of Prof. Raju Chaganti at the Memorial Sloan Kettering Cancer Center, New York USA as a postdoctoral research associate. This appointment provided me an excellent opportunity to engage in cancer research where I could apply my cytogenetic and molecular biology skills to understand the genetic basis of lymphoma, the primary focus of Dr. Chaganti’s laboratory. I was involved in the cloning and characterization of several immunoglobulin heavy chain genes (IGH) associated with chromosomal translocations and cognate gene fusions (IGH-MUC1; IGH-FGFR2; IGH IRTA1-2; IGH-CHST11; IGH-PAX5) that resulted in publications in top tier journals including Blood, Cancer Research and Immunity.  With a background and skills in cancer genetics, molecular biology and an understanding of the growing importance of chromosomal rearrangements and associated gene fusions in cancer, I became interested in translating the laboratory discoveries into diagnostic tools to benefit cancer patients. In 1999, I accepted a position as Director of Research and Development at Cancer Genetics, Inc, Boston, MA. There, I developed diagnostic reagents based on fluorescent in situ hybridization technology. My research work at Cancer Genetics Inc. was funded by four consecutive Phase I and one Phase II SBIR grants as Principal Investigator. Two patents have been granted recently (US patents #7585964; 7964345) for the novel approaches I developed for analyzing chromosomal translocations using fluorescence in situ hybridization. I returned to academia as a group leader in Cancer Biology at the Genome institute of Singapore, Singapore, where I independently established the molecular cytogenetics laboratory. My work on the identification of gene fusions in lymphoma led to my hypothesis that similar recurrent gene fusion may occur in epithelial cancers. I selected breast and gastric cancers as models and employed novel approaches based on high density oligonucleotide microarrays and paired end ditag-sequencing approaches to study the complex chromosomal rearrangements and copy number changes. Utilizing newly developed tools, a novel recurrent gene fusion involving CD44-SLC1A2 genes was discovered, the results of which were published in Science Translational Medicine. After a three year stay at the Genome Institute of Singapore, I accepted a position at the Michigan Center for Translational Pathology, University of Michigan. Here, I continued my efforts in identifying new cancer biomarkers in epithelial cancers. Following the discovery of recurrent gene fusions in prostate cancer by Arul Chinnaiyan’s group in a subset of prostate cancer, I was interested in understanding the genetic basis of the gene fusion-negative subset of prostate cancer. Using the emerging and powerful next generation sequencing technology, I discovered recurrent gene fusions involving the RAF kinase family genes that can be targeted with existing FDA approved drugs that could benefit a subset of prostate cancer patients. By extending the screening for the presence of RAF gene fusions in other epithelial cancers, a small subset of melanoma and gastric cancers were also found to harbor RAF kinase rearrangements. The discovery of RAF gene fusions in three different epithelial cancer lead to a new paradigm in classifying cancers based on molecular aberrations rather than morphological and tissue-based classification. Over the course of my research career I have adopted newly developed molecular and cytogenetic tools and applied them successfully for the discovery of important cancer-specific biomarkers and have developed diagnostic tools for routine diagnosis and follow-up treatment in the clinics. My work has made a great impact in cancer research and I was able to accomplish this by maintaining an independent research program while playing key roles in large team projects at various institutions to make important high-impact contributions to advance cancer research.

 My current research interests are centered on the discovery and characterization of gene fusions in solid cancer and their role in carcinogenesis from a translational research perspective. I have been using genomic technologies such as aCGH, FISH, SKY, gene expression microarrays, and next-generation sequencing (NGS) to interrogate the transcriptional and genomic architecture of solid cancer genome. At the DNA level, in-depth analyses using high resolution technologies to study copy number changes, particularly genomic amplifications and deletions, have identified rare gene fusions formed at the boundaries of copy number changes. At Michigan Center for Translational Pathology (MCTP), we pioneered the application of next generation sequencing technology for transcriptome sequencing and discovered new recurrent gene fusions in cancer. The primary goal of this approach is to identify novel gene fusions specific for each cancer type. The discovery of recurrent gene RAF gene fusions in non ETS prostate cancer and identification of cancer specific expression of pseudogenes was made possible by these novel computational approaches.