2020 Grantee: Krushna Patra, PhD
University of Cincinnati
Research Project: Delineating Oncogenic Circuitries of GNAS Mutant Pancreatic Neoplasms
Award: 2020 Pancreatic Cancer Action Network Career Development Award, funded by Steven & Cheryl Kole and Harriet & Gerald Berner Family Charitable Fund
Award Period: Sept. 1, 2020 – Aug. 31, 2022
Dr. Patra earned his master’s degree from the Indian Institute of Technology, Kharagpur, India. He received his PhD in biochemistry and molecular genetics from the University of Illinois at Chicago, where he investigated the regulation of hyperactive glucose metabolism in cancer (the breakdown of sugar for cellular building blocks and energy).
Dr. Patra then joined the laboratory of Dr. Nabeel Bardeesy (recipient of the 2008 PanCAN Randy Pausch, PhD – Pilot Grant) as a postdoctoral fellow at Massachusetts General Hospital Cancer Center/Harvard Medical School. During Dr. Patra’s postdoctoral studies, he generated novel animal models that develop pancreatic cancer from intraductal papillary mucinous neoplasm (IPMN) precursor lesions (precancerous cysts). His research has identified signaling and metabolic pathways that support tumor growth in this distinct subset of cancer.
In 2019, Dr. Patra joined the department of cancer biology at the University of Cincinnati as an assistant professor, where his laboratory investigates how early events in pancreatic cancer define the development and progression of this devastating disease. Research from his laboratory will help to better understand this disease and potentially uncover novel therapeutic strategies for pancreatic cancer.
The poor outcome in the treatment of pancreatic cancer patients is due in part to the lack of early detection and inadequate understanding of the function of tumor-causing genes. Hence there is a tremendous effort to identify high-risk patient populations who are susceptible to developing pancreatic cancer. Individuals with pancreatic cysts can be considered part of a high-risk group; they can develop pancreatic cancer if they carry cancer-causing genetic mutations. Pancreatic cysts are very common (up to 8%) in asymptomatic older individuals over the age of 70 and frequently detected in CT scans. Because of the high frequency and poor understanding of the disease, the patients are either over- or undertreated, which creates an economic burden on the healthcare system.
Intraductal papillary mucinous neoplasms (IPMN) are one of the cystic lesions of the pancreas. About 50-60% of IPMNs have cancer-associated activating mutations in the GNAS gene, and a significant fraction of IPMNs progress to pancreatic cancer. The focus of Dr. Patra’s proposal is to gain insights into a subset of pancreatic tumors that arises through IPMNs with mutations in the GNAS gene.
Recently, Dr. Patra and his team used mouse models and human tumor cells to discover that pancreatic cancers with GNAS mutations have several important differences from other subsets of pancreatic cancers, regarding the biochemical processes required to sustain tumor growth. Most importantly, blocking the function of GNAS or a set of proteins that are regulated by mutant GNAS is very effective in preventing the growth of this subclass of tumors in experimental model systems.
Building on their extensive preliminary findings, the goals of this proposal are to gain a more complete picture of mutant GNAS-regulated proteins involved in gene expression and metabolic processes that support tumor growth. The investigators’ research will help to guide clinical decisions and develop optimized approaches to successfully treat this poorly understood subtype of pancreatic cancer that can be detected in its early phase of development.