JT Poirier, PhD

My research program is dedicated to uncovering the fundamental biological principles of lung cancer progression and treatment response. By integrating advanced functional genomics with high-fidelity patient-derived models, we bridge the gap between clinical observation and mechanistic discovery. As Director of Functional Genomics, my goal is to identify the genetic and epigenetic drivers that dictate a tumor’s biological trajectory, focusing on why specific evolutionary paths lead to therapeutic failure.

Uncovering the Biological Determinants of Drug Sensitivity

We seek to understand the mechanistic basis of drug sensitivity. We use forward-genetic screens to map the complex regulatory networks such as those governing replication stress and DNA damage repair that dictate a cell's biological fitness under therapeutic stress. By following the biology revealed by these screens, we characterize the intrinsic vulnerabilities that define the baseline landscape of treatment response in lung cancer.

Modeling the Evolution of Resistance

A central pillar of our lab is the study of acquired resistance as a dynamic biological process. We develop genome engineering technologies that allow us to orchestrate and study large numbers of genetic variants in parallel, effectively accelerating cancer evolution in the lab. This approach enables us to uncover the molecular logic behind resistance, identifying how specific genetic variants allow cancer cells to bypass treatment and adopt new, treatment-resistant phenotypes.

Integrated Target Discovery and Preclinical Validation

To translate these insights into the clinic, we maintain a robust pipeline for discovering novel or underdeveloped therapeutic targets. By leveraging patient-derived xenografts (PDX) and viable human tumor cells, we validate our genomic findings in high-fidelity models that mirror clinical complexity. Our goal is to transform the discovery of lineage-specific vulnerabilities into actionable diagnostic and therapeutic targets, ultimately establishing more durable treatment paradigms for patients with lung cancer.