Ashu Shah, PhD, is an Assistant Professor for the Department of Biochemistry and Molecular Biology at the UNMC College of Medicine. Her current research focuses on understanding the intricacies of pancreatic cancer, identifying novel targets and developing antibody-based therapies. The lab's research interests focus on developing a future generation of monoclonal antibody (mAb)-based strategies with novel, enhanced functions that offer new options for cancer patients. We are developing various antibody formats, including scFv, Fabs, humanized antibodies, antibody-drug conjugates, Fc-engineered antibodies and CAR-T constructs, for targeting MUC16 in pancreatic cancer. Dr. Shah utilizes phage display, structure modeling and next-gen antibody engineering tools to develop these antibody drugs. These antibody candidates are tested for their biophysical (integrity and stability) and biochemical (specificity, affinity and binding) properties, as well as therapeutic efficacy in both in vitro and in vivo mouse models. The team plans to evaluate the efficacy of these antibody candidates in various animal models, including orthotopic xenografts and syngeneic, transgenic and FcR-humanized mouse models. As a translational cancer researcher, Dr. Shah aims to engineer mAbs to modulate the immune milieu of pancreatic cancer by endowing the Fc domain with immune-engaging functions or delivering immunomodulatory or toxic agents to the TME.

Another significant aspect of Dr. Shah’s research involves understanding the involvement of perineural invasion (PNI) in the pathobiology of pancreatic cancer. The phenomenon of PNI involves the invasion of tumor cells into surrounding nerve bundles and is associated with poor prognosis, metastasis, and pain in cancer patients. The team is currently delineating the role of neuropilin-2 (NRP2) in PNI and cancer-associated pain in pancreatic cancer patients. Dr. Shah’s research focuses on investigating the complex, bidirectional crosstalk between cancer cells, peripheral nerves and tumor microenvironment (TME) to understand their contributions to cancer, PNI and neuropathic pain. These studies will reveal new opportunities and strategies to interrupt these co-morbidities and improve the overall quality of life of PDAC patients. In parallel, the research team is delineating the molecular implications of NRP2 in PDAC pathobiology by developing a conditional NRP2 knockout mouse model of pancreatic cancer.