Beatriz Sosa-Pineda, PhD
Professor, Nephrology; Feinberg School of Medicine
Research Program
Cancer-Focused Research
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer, with a 5-year survival rate of less than 5%. In my lab we use mouse models of the disease and primary cultures from their resected pancreatic tumors to study various aspects of pancreas tumorigenesis. We are very interested in revealing how pancreatic acinar cells acquire a âplastic phenotypeâ under the influence of oncogenic Kras and give rise to precancerous lesions. We also want to understand how the function of ATM (a kinase involved in DNA damage responses) poses a barrier to pancreatic cancer progression. ATM activity is necessary to prevent widespread DNA damage and we determined that ATM deficiency synergizes with oncogenic Kras to promote the formation of highly metastatic PDAC in mice. In agreement with these results, GWAS studies identified ATM deleterious mutations in human pancreatic tumors classified as âgenetically unstableâ and in close to 5% of patients with hereditary pancreatic cancer. Thus, our mouse models of ATM deficiency have clinical relevance and will be used to identify potential novel therapies. Our ATM-deficient and ATM-proficient tumor cell lines are also an invaluable complement for our studies in vivo.