Research Seminar Speaker Series-Cecily Anaraki, PhD Candidate, UCI-“Differential Stress Responses Drive Asparagine Exchange in Pancreatic Cancer”

Please join us for our Research Seminar Series Speaker, Cecily Anaraki, PhD Candidate, UCI presentation on:

Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related death in the United States. A principal barrier to treatment is the densely fibrotic tumor microenvironment, paired with high interstitial pressure which acts to collapse blood vessels and impair the delivery of chemotherapy. This lack of functional vasculature limits nutrient availability within the tumor, causing cancer cells to develop numerous metabolic adaptations to allow for proliferation. Exploring this, we found distinct metabolic profiles and sensitivities in a series of clonal cell lines derived from a single pancreatic tumor. These groups demonstrated differential sensitivities to mitochondrial inhibitors, and the growth of these sensitive clones during impaired respiration can be rescued through co-culture with insensitive cells. By profiling metabolites exchanged by the clonal populations, we identified this is mediated via asparagine released by insensitive cells. Mechanistically, the production of asparagine is driven by differential stress response pathway activation between clones. Additionally, we found that the use of asparaginase to degrade asparagine sensitizes PDA tumors to mitochondrial inhibition. Collectively these data demonstrate distinct metabolic classes of cancer cells within single tumors and identify asparagine as a potential target to sensitize tumors to mitochondrial inhibition.

Date: Friday, October 14, 2022

Time:  12:00 – 1:00 p.m.

Location: 121 Bldg. – 1111 Classroom & Via Zoom (See Outlook invite for Zoom Link)