Michelle Krogsgaard, Ph.D.

Research

At the Krogsgaard laboratory, we investigate the molecular and cellular events that regulate T-cell sensitivity to "self" (cancer) antigens, including those found in cancer cells, as well as neoantigens, with a focus on antigen discovery. Our interdisciplinary approach integrates cutting-edge biophysical techniques—such as surface plasmon resonance (SPR), X-ray crystallography, and nuclear magnetic resonance (NMR) spectroscopy—with advanced imaging methods such as single molecule imaging and FRET, alongside innovative transgenic TCR technologies. A key focus of our work is studying human T cells using multiomics approaches to comprehensively analyze the signaling pathways and protein-protein interactions involved in T-cell activation and function. This enables us to identify therapeutic targets and biomarkers for precise modulation of immune responses and minimizing immune-related adverse events. By integrating these methods, our work not only advances understanding of immune function but also supports the development of novel therapies. We aim to pharmacologically modulate TCR signaling to enhance T-cell sensitivity in cancer and HIV or reduce it in autoimmune disorders such as multiple sclerosis or diabetes. Our research strives to advance immunotherapy by providing novel strategies to precisely control immune responses for improved treatment outcomes, while addressing challenges such as immune-related adverse events.

As an Innovation Fund investigator, Michelle Krogsgaard, Ph.D., is teaming up with Richard L. Possemato, 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.