Lustgarten Foundation-AACR Career Development Awards for Pancreatic Cancer Research
The Lustgarten Foundation-AACR Career Development Award for Pancreatic Cancer Research, in Honor of John Robert Lewis, represents a joint effort to encourage and support early career scientists engaged in pancreatic cancer research who are members of racial or ethnic groups that have been shown to be underrepresented in the cancer-related sciences workforce. The Lustgarten Foundation-AACR Career Development Award for Pancreatic Cancer Research, in Honor of Ruth Bader Ginsburg, represents a joint effort to support the career advancement of a female scientist engaged in pancreatic cancer research.
Pancreatic adenocarcinoma (PDAC) is a poorly immunogenic tumor characterized by low mutational burden and limited responses to immunotherapies. PDAC tumors, similar to other solid tumors, exhibit alterations of cellular glycosylation, including the abundant expression of the truncated O-glycan Tn antigen. Tn antigen is the ligand for the macrophage galactose-type lectin (MGL) expressed by tolerogenic antigen presenting cells and M2-phenotype macrophages. Using single-cell RNA sequencing of tumor immune infiltrate and bone marrow, Dr. Posey seeks to determine how the Tn antigen shapes the PDAC immune microenvironment as well as the systemic immune composition. In addition, he plans to adoptively transfer anti-Tn CAR-T cells to mice bearing heterogeneous Tn+ PDAC tumors to test whether disrupting the MGL-Tn axis will decrease the local immunosuppression within the tumor and improve anti-tumor responses in PDAC tumors.
Dr. Posey has BS degrees in biochemistry and bioinformatics from the University of Maryland, Baltimore County (UMBC), and a PhD in genetics from the University of Chicago. He completed postdoctoral training at the University of Pennsylvania, where he generated glycosylation-specific chimeric antigen receptors to precisely target tumor glycoforms of MUC1. He is currently an assistant professor in the Department of Systems Pharmacology and Translational Therapeutics at the University of Pennsylvania, a member of the Parker Institute for Cancer Immunotherapy, and a research health scientist at the Philadelphia Veterans Administration Medical Center.
Acknowledgment of Support
I am grateful to accept the Lustgarten Foundation-AACR Career Development Award for Pancreatic Cancer Research, in honor of John Robert Lewis. This award will support and expand my laboratory’s scientific enterprise. Importantly, we will investigate an underappreciated immune axis in pancreatic cancer and devise therapeutic strategies to eventually benefit patients.
Dr. Engle has previously shown that aberrant glycan CA19-9 expression accelerated pancreatic tumor progression and increased metastatic dissemination in mice. In this work, she aims to elucidate the cell intrinsic and extrinsic roles of CA19-9 in pancreatic cancer metastasis. Using models of liver metastasis in monobiotic and parabiotic hosts, she and her team are set to identify the CA19-9 modified ligands that contribute to remodeling the local and distal microenvironment. In addition, they plan to characterize the signaling alterations that occur in the liver (the primary site of pancreatic cancer metastasis) in the presence of CA19-9 produced by the pancreas, using organoid co-culture approaches. Thirdly, they plan to assess the impact of abrogating the CA19-9 receptor E-selectin on metastatic dissemination and gene expression programs.
Dr. Engle received her BA in biological sciences and Asian & Middle Eastern studies from Northwestern University. She completed her doctorate in biology at the University of California, San Diego and the Salk Institute for Biological Studies. After completing her postdoctoral fellowship at the Cambridge Research Institute in England and Cold Spring Harbor Laboratory, she was recruited to start her own laboratory at the Salk Institute. Dr. Engle is also the recipient of an NCI Career Transition Award, the Theodore T. Puck Award, and other notable distinctions.
Acknowledgment of Support
Having lost close family members to pancreatic cancer, it has been my dream to start a dedicated pancreatic cancer research lab. The Lustgarten-AACR Career Development Award, in honor of Ruth Bader Ginsburg will enable me to harness my personal and scientific passion to make inroads against this devastating disease.