On Friday, November 12th @ 11:00AM ET, we welcome Prof. Ashley Laughney from Weill Cornell Medicine as she presents, "Systems analysis of tumor-microenvironment crosstalk induced by chromosomal instability."
ABOUT THE SEMINAR
Systems analysis of tumor-microenvironment crosstalk induced by chromosomal instability
Chromosomal instability (CIN) is associated with cancer metastasis and immune evasion. How CIN shapes the tumor microenvironment (TME) to facilitate metastatic progression is poorly understood. Here, we show that chronic activation of the cytosolic DNA sensing cGAS-STING pathway by CIN promotes a rich granulocytic infiltrate and immune suppressive microenvironment. Using ContactTracing, a newly developed computational method to infer conditionally-dependent cell-cell interactions from single cell RNA sequence data, we identify a tumor cell-derived secretome associated with ER-stress arising from chronic STING signaling. Suppression of CIN or depletion of tumor cell STING reduces ER-stress and restores a proinflammatory TME. Moreover, pharmacologic inhibition of chronically active STING, or genetic knockout of key mediators of its ER stress/unfolded protein response, suppresses metastasis in syngeneic models of melanoma, breast, and colorectal cancers. Thus, inhibition of chronic STING signaling might represent a viable therapeutic strategy in chromosomally unstable metastatic cancers.
ABOUT THE SPEAKER
Ashley Laughney, Ph.D., Assistant Professor of Physiology & Biophysics, Institute for Computational Biomedicine, Meyer Cancer Center, Weill Cornell Medicine
In 2019, Ashley joined the faculty at Weill Cornell Medicine. Her NCI-supported laboratory utilizes high-throughput single cell sequencing and quantitative imaging technologies, synthetic biology tools, as well as mouse models of metastasis, to mechanistically dissect tumor cell heterogeneity through the lens of tissue regeneration and repair. By integrating systems biology methods within a hypothesis driven framework, her goal is to better understand the adaptive abilities of tumor cells and their interplay with anti-tumor immunity. Her lab is affiliated with the Institute for Computational Biomedicine, the Department of Physiology, Biophysics and Systems Biology, the Tri-Institutional PhD Program in Computational Biology and Medicine, and the Meyer Cancer Center at Weill Cornell Medicine.
ABOUT THE 2021-2022 BME SEMINAR SERIES
The Department of Biomedical Engineering at Columbia University is proud to host an annual weekly seminar series on the latest developments and research in Biomedical Engineering. The weekly series takes place on Friday mornings at 11:00AM Eastern and includes a variety of renowned academics from top universities to talk about their specific research and experience. This is a hybrid event.