BLRD Research Career Scientist Award Application

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Dr. Pran K. Datta is currently a Research Microbiologist at the Birmingham VA Medical Center (BVAMC), AL, and a Professor at the VA-affiliated University of Alabama at Birmingham (UAB). He has a long-standing track record in the mechanistic studies of colorectal (CRC) and lung cancer. Since 2010, he has been contributing significantly to VA research and services through training, mentoring, and collaboration with VA investigators. His established expertise in basic and translational cancer research has also attracted investigators from diverse disciplines at the VA Medical Centers in the US, Vanderbilt University, and UAB, which has led to collaborative grants and high-impact publications. A seminal discovery from Dr. Datta's lab is the identification and cloning of a TGF-ß-receptor binding protein STRAP (Serine Threonine Kinase Receptor Associated Protein) that inhibits TGF-ß signaling and activates Wnt/ß-catenin and Notch signaling. The second seminal contribution of his study is to establish the role of STRAP in activating the stemness of cancer stem-like cells. His third seminal contribution is to identify a smoking-regulated miRNA signature that promotes NSCLC progression and chemoresistance. His high impact research resulted in more than 70 papers and reviews in reputable top-tier scientific journals (some of them with impact factor range 8.7-22.7). The fundamentals of the following projects are based on these high impact and highly cited papers. Around 20 of his papers are cited more than 100 times each. Project I: Translational research on colorectal cancer (CRC) pathogenesis and targeting by nanotherapy. During the last 40 years, the proportion of CRC has increased by about 15% in the veteran population and thus constitutes a significant risk for all veterans and their family members, including women, especially over 50 years of age. Consistent with this, there were more than 52,000 new cases of colorectal cancer cases in VA during the last 5 years. To combat this problem, the PI's lab will therapeutically target the pro-oncogenic functions of STRAP by siRNA-based nanoformulation in potential treatment of CRC patients as well as by sensitizing 5-FU and/or Oxaliplatin based chemotherapy. Project II: Circulating microRNAs as predictive biomarkers for brain metastasis in non-small cell lung cancer (NSCLC). Consistent with the fact that lung cancer remains the leading cause of cancer death in the US veteran population, there were 41,780 new lung cancer cases and 19,543 lung cancer deaths among the VA population during the last 5 years. The percentage of active-duty military personnel who smoked was highest during the Vietnam and Korean Wars (75%). Similarly, 60% of Afghanistan and Iraq War veterans used tobacco. The death records of 52,000 veterans of Vietnam War showed that these veterans died of lung cancer at a 58% higher rate than veterans who did not serve there. To this end, Dr. Datta's lab is trying to identify a miRNA signature in primary lung tumors that predicts NSCLC metastasis to the brain. Then this miRNA signature will be validated using serum to stratify NSCLC patients at high risk for developing brain metastasis and investigate their function in NSCLC progression and metastasis. In addition to conducting these highly innovative and high impact research programs, Dr. Datta has been recognized for his exceptional contributions to training, mentoring, and services at the local and national VA. As the Director of Research in the Hematology and Oncology Division and of the T32 Training Grant, Dr. Datta oversaw the research development and mentored junior faculty and clinical and postdoctoral fellows; a number of those are in academia with high positions. Taken together, the RCS Award is expected to assist him develop high-impact diagnostics and therapies for veterans and other Americans in need.