BLRD Research Career Scientist Award Application

Although CRC endangers males and females of all the population, the US (the United States of America) Veterans show a higher incidence rate of colon cancer than the general population. It is estimated that each year the Veterans affairs manages and treats ~175,000 CRC patients. It is therefore an urgent necessity to find novel therapeutic strategies to curb CRC-malignancy to

increase the overall survival for the U.S. Veterans diagnosed with CRC as well as improve their quality of life. Characterization of the key molecules involved in the processes critical for CRC progression to develop novel and promising therapeutic approaches not only holds the promise of decreasing the patient mortality amongst VA-CRC patients but also reduce the associated

financial burden for the Veterans Administration. The applicant’s lab program is focused on understanding the molecular mechanism/s involving dysregulation of specific tight junction and cell cycle proteins in Colon cancer progression and metastasis and developing targeted therapeutics. Her laboratory is internationally known for its contributions in this area, especially in

understanding the role of Claudins in regulating CRC progression to metastasis and resistance to conventional therapy. In this regard, extensive preclinical and clinical studies from her laboratory, have validated a casual role for upregulated claudin-1 expression in promoting CRC metastasis. Her laboratory is also the 1st lab which has developed a novel inhibitor for inhibiting

claudin-1 for inhibiting CRC. Her laboratory further demonstrated that claudin-7, yet another claudin family protein, is a tumor suppressor in colon cancer. Her laboratory is also developing patient-derived organoids, tumor xenografts from known disease stages and variable therapeutic response, or have access to such reagents through her collaborations. The applicant has a broad

background in cancer biology, with published expertise in the regulation of colon carcinogenesis and metastasis using in vivo and in vitro mouse, organoid and cell culture models. As a Research Career Scientist, she will oversee this research program by coordinating the work done; designing the experiments, delegating the work and monitoring the work to ensure that it progresses in a

timely fashion. She will also be involved in preparing manuscripts of the work performed and presenting the results at conferences in this area of cancer biology, therapeutics in CRC patients. Applicant’s research program has been continuously funded by VA Merit Award and multiple NIH- grant awards for ~17-years. She has extensively published her laboratory work in over 75 original

peer reviewed research articles in prestigious journals in the field including Gastroenterology (impact factor 33), GUT (Impact Factor 31) and J Clin Invest (19.4). In addition, one of the key hallmarks of her program has been a multidisciplinary and collaborative nature of the research enterprise with a deep focus on mentoring new generation of VA and affiliated university

investigators to enable them to establish their own independent research programs. She has been successful at both the fronts: making new discoveries in the field and mentoring new generation of young scientists and establishing a solid research environment at our local VA as well as at affiliated university. This current application is intended to highlight the success of our program

and requesting RCS program to help us progress towards the new heights of success by nurturing and mentoring a new generation of investigators.