Trainee Spotlight: Sanjeevani Arora, PhD
Drs. Erica Golemis’, PhD, and Greg H. Enders’, MD, PhD, Labs
Fox Chase Cancer Center
I was drawn to biology and chemistry from very early on in life. My father is a physician-scientist who would always discuss his experiences from the clinic and his research. By the time I started high school, I knew I wanted a career in biology, but I never planned on becoming a researcher until later experiences put me squarely on this path. During my undergrad at Bangalore University, Bangalore, India, I worked with Dr. Geetha Viswananthan and her team of undergraduate research assistants. I was involved in data collection and analysis, as well as writing a manuscript. This was a life changing experience for me; I fell in love with the process of research and team science. After completing a graduate degree in Biotechnology, I started as a Clinical Laboratory Fellow at the highly reputed Gujarat Cancer Research Institute, Gujarat, India. During this time, I worked closely with cancer patients processing blood samples, running diagnostic tests, preparing and delivering their reports. Through this process, I realized that there was a lack of effective biomarkers in the clinic for cancer detection and assessing treatment efficacy. At this point I was really interested in broadening my knowledge of cancer biology and cancer genetics. With this goal, I decided to pursue a PhD in Biomedical Sciences. I joined the University of Toledo’s (Health Science Campus) doctoral program and got my PhD with Dr. Steve Patrick from the Department of Biochemistry and Cancer Biology. As a doctoral student, I gained expertise in understanding the role of DNA repair mechanisms in chemotherapeutic resistance in cancer. As I was finishing up doctoral work, I was interested in continuing in the area of cancer diagnostics and therapeutics. Hence, in the fall of 2012, I joined Greg Enders’ lab at Fox Chase Cancer Center (FCCC) for postdoctoral work. In late 2014, Greg Enders left FCCC to pursue a full-time clinical practice and I continued my postdoctoral work with Erica Golemis. My current project focuses on genetically defining undiagnosed familial colorectal and prostate cancers. My future plans are to understand how defects in low to moderate penetrance DNA damage response genes could link predisposition to familial cancers and thus provide the basis for effective cancer risk assessment.
Approximately 20-30% of Familial Colorectal Cancers (FCRCs) remain genetically undefined leading to ineffective screening for individuals at risk and overscreening of individuals not at risk. Thus the aim of this project was to genetically characterize undefined FCRC (uFCRC) cases from the Family Risk Assessment Program (FRAP) at FCCC. The main findings of this study were: 1) Germline variants in low- to- moderate- risk genes that maintain the integrity of DNA double strand breaks (DSBs) repair pathways are commonly present in uFCRC patients; 2) There is a 7-fold higher frequency of these germline variants in uFCRC patients as compared to cancer-free control population. 3) Importantly, we showed that primary T-cells from patients show increased markers of DNA DSBs when treated with low-doses of DNA damaging agents, which helped segregate these individuals from cancer-free controls and sporadic CRC cases (P<0.001). These data suggest that germline variants in the DSB repair pathway lead to the accumulation of genomic instability and predispose expressers to uFCRC and potentially other cancers. Our work provides the evidence for the existence of a constitutional genomic instability in a subset of uFCRC due to a defect in suppression of DNA DSBs. This study provides the basis for the development of a potential screening tool to improve screening and diagnosis as well as provide genetic counseling to predict risk within families. A patent on this new method of detection has been filled and is currently under review.
Genetic Variants That Predispose to DNA Double-strand Breaks in Lymphocytes from a Subset of Patients With Familial Colorectal Carcinomas.
Arora S, Yan H, Cho I, Fan HY, Luo B, Gai X, Bodian DL, Vockley JG, Zhou Y, Handorf E, Egleston BL, Andrake M, Nicolas E, Serebriiskii I, Yen TJ, Hall MJ, Golemis EA, and Enders GH. Gastroenterology. 2015 Sep 4. pii: S0016-5085(15)01259-7.
Ed. Note: In July, 2017, Dr. Arora was appointed an Assistant Research Professor at Fox Chase Cancer Center.