Richard L. Possemato, Ph.D.

Research

Our laboratory is dedicated to understanding alterations in metabolism in human disease, focusing on nutrient sensing and the response to nutrient deprivation in cancer. Our long-term goal is to understand metabolic pathways altered in disease, processes that these pathways support, and the environmental, genetic, and epigenetic contexts in which these pathways are important. We accomplish this goal using genetic screening in mammalian systems coupled to mechanistic follow-up using metabolomic and cell biology-based approaches in cellular and mouse cancer models. Our laboratory has specifically focused on iron and nucleotide sensing and feedback control mechanisms, oxidative stress signaling, and leading strand replication.

As an Innovation Fund investigator, Richard L. Possemato, Ph.D., is teaming up with Michelle Krogsgaard, Ph.D., to explore how metabolic limitation impairs effector T-cell function and to identify strategies to enhance T-cell function in metabolically hostile environments such as tumors. The team aims to define the nutrient conditions and metabolic genes that support T-cell expansion and cancer cell elimination. They will then characterize T cells from patients with triple-negative breast cancer undergoing immune checkpoint inhibitor therapy to uncover metabolic programs associated with therapeutic response. The project combines the Possemato lab’s expertise in high-throughput genetic screening of cellular metabolism with the Krogsgaard lab’s extensive experience in T-cell receptor signaling and its relevance to cancer immunotherapy. Together, their work will generate a prioritized list of nutrient environments and gene targets that enhance T-cell effector function in metabolically challenging settings. These findings could inform the rational design of metabolic interventions that complement immunotherapy.