Jad Belle

MSTP in PhD Training

Program: Molecular Genetics and Genomics

Current advisor: David G. DeNardo, PhD

Undergraduate university: McGill University, 2011

Enrollment year: 2016

Research summary
Stromal senescence in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal solid malignancy with a 5 year survival rate of 8%. Most patients are diagnosed at metastatic stages and treatments are largely ineffective. The refractory nature of PDAC has been attributed to its characteristic tumor microenvironment (TME) which comprises 70-80% of tumor mass. The TME is composed of an abundance of immunosuppressive myeloid cells and cancer-associated fibroblasts (CAFs) in a dense fibrotic matrix. Recent single cell transcriptomic studies have identified phenotypically heterogeneous CAF subsets but their specific functions remain unexplored. My project is focused on determining the role of a senescent CAF subset in PDAC biology and therapeutic resistance.

Graduate publications
Lander VE, Belle JI, Kingston NL, Herndon JM, Hogg GD, Liu X, Kang LI, Knolhoff BL, Bogner SJ, Baer JM, Zuo C, Borcherding NC, Lander DP, Mpoy C, Scott J, Zahner M, Rogers BE, Schwarz JK, Kim H, DeNardo DG. 2022 Stromal reprogramming by FAK inhibition overcomes radiation resistance to allow for immune priming and response to checkpoint blockade. Cancer Discov, 12(12):2774-99.

Su X, Xu Y, Fox GC, Xiang J, Kwakwa KA, Davis JL, Belle JI, Lee WC, Wong WH, Fontana F, Hernandez-Aya LF, Kobayashi T, Tomasson HM, Su J, Bakewell SJ, Stewart SA, Egbulefu C, Karmakar P, Meyer MA, Veis DJ, DeNardo DG, Lanza GM, Achilefu S, Weilbaecher KN. 2021 Breast cancer-derived GM-CSF regulates arginase 1 in myeloid cells to promote an immunosuppressive microenvironment. J Clin Invest, 131(20):e145296.