Aram F. Hezel

Aram Hezel is a physician-scientist and translational oncologist with foundational contributions to understanding the molecular biology of pancreatic ductal adenocarcinoma (PDAC), with a particular focus on KRAS effector signaling, the tumor suppressor LKB1/STK11, and DNA damage response pathways in pancreatic cancer. He serves as Chief of the Division of Hematology/Oncology at the University of Rochester Medical Center and Wilmot Cancer Institute. Hezel's early research, conducted during his training at the laboratory of Ronald DePinho, made critical contributions to defining the functional landscape of tumor suppressor inactivation in pancreatic cancer. He generated and characterized genetically engineered mouse models in which Lkb1 (also known as Stk11) — encoding the serine-threonine kinase LKB1 that regulates cellular energy sensing through AMPK pathway activation — was conditionally deleted in the pancreatic epithelium in combination with oncogenic Kras. These studies demonstrated that LKB1 loss dramatically accelerates pancreatic tumor formation, promotes PDAC progression with altered metabolic dependencies, and confers distinct therapeutic vulnerabilities. LKB1 loss in pancreatic cancer is now understood to reprogram cancer cell metabolism, suppress antitumor immune responses, and alter sensitivity to mTOR pathway inhibitors. In parallel, Hezel's work has addressed the role of DNA damage response (DDR) pathway alterations in PDAC. He contributed to characterizing how loss of BRCA1/2, ATM, and other DDR genes sensitizes pancreatic cancer cells to DNA-damaging agents and PARP inhibitors, providing the molecular rationale for olaparib maintenance therapy in germline BRCA-mutant PDAC — which received FDA approval based on the POLO trial. Hezel's laboratory has also investigated crosstalk between KRAS effector pathways and tumor-stroma interactions, and has developed models to study how the physical and signaling microenvironment of PDAC influences therapeutic response. As an institutional leader at URMC/Wilmot Cancer Institute, he has expanded the GI oncology and translational research programs and developed collaborative networks with academic cancer centers.

Aram Hezel 是一位医师-科学家和转化肿瘤学家，在胰腺导管腺癌的分子生物学方面做出了基础性贡献，尤其关注KRAS效应信号传导、肿瘤抑制因子LKB1/STK11和DNA损伤应答通路。他担任罗切斯特大学医学中心血液学/肿瘤学部门主任。 Hezel 在Ronald DePinho实验室进行的早期研究通过建立Lkb1条件缺失联合KrasG12D胰腺癌小鼠模型，证明LKB1缺失显著加速胰腺肿瘤形成，重编程癌细胞代谢，并影响对mTOR通路抑制剂的敏感性。他还通过研究BRCA1/2、ATM等DDR基因缺失如何致敏胰腺癌细胞，为奥拉帕尼维持治疗胚系BRCA突变PDAC提供了分子基础。