Exploring epigenetic regulation of T cell adaptive immunity
Immune cell-based therapies have emerged as a promising new tool in the fight against cancer and chronic infections. Prolonged stimulation of T cells leads to “exhaustion” and limits their ability to function. We use a combination of epigenetic and computational techniques to study this T cell exhaustion. Our laboratory wants to understand the mechanisms that regulate the development of T cells during infection, cancer, and autoimmunity with the goal of improving treatments for these diseases.
Following chronic stimulation, T cells undergo a developmental process known as “exhaustion,” a dysfunctional state reinforced by epigenetic changes that limits their capacity to mount an effector response. The commitment of T cells to this exhausted fate is currently a major barrier in the advancement of T cell immunotherapy efforts. Our lab discovered that T cells can resist exhaustion when a particular enzyme is knocked out – even if the source of antigen persists. We are now applying this perturbation approach to CAR T cells, creating persistent populations of functional cells that we can now evaluate in clinical trials at St. Jude.
Our laboratory employs cutting-edge epigenetic and transcriptional profiling techniques, gene engineering approaches in human and murine models of T cell exhaustion, and computational analyses to identify molecular mechanisms of T cell exhaustion. We then work to develop innovative strategies to block exhaustion and prolong T cell responses during immunotherapy. This work not only provides insight into the process of T cell exhaustion, but also reveals clues to improve T cell-based immunotherapies.
We are actively extending our research toward immuno-oncology, specifically the tumor microenvironment’s role in T cell differentiation and how we can leverage our previous discoveries to better understand tumor immunology.
Dr. Benjamin A. Youngblood is currently an associate member in the Department of Immunology at St. Jude. After his graduate training in biochemistry at UCSB, he joined Dr. Rafi Ahmed’s lab in 2007 as a postdoc studying epigenetic regulation of memory CD8 T cell differentiation. Since 2014, Dr. Youngblood has been vital part of the St. Jude community, developing a robust research program to inform our understanding of viral infection, cancer and autoimmunity. Based on his accomplishments and expertise, he was invited to serve on the prestigious Stand Up to Cancer Epigenetics Dream Team.
Team of biological and clinical scientists focused on translating fundamental immunological discoveries into therapies.