“Choosing the T-cell profession: the mechanisms within” Keynote Talk

About

"Choosing the T-cell profession: the mechanisms within" Dr. Ellen Rothenberg (Distinguished Professor of Biology, California Institute of Technology; A.D. White Professor-at-Large at Cornell) Thursday, November 19, 2026 4:00pm ⋅ Lecture Hall 5, College of Veterinary Medicine Open to all ⋅ Reception to follow in CVM Atrium.

An A.D. White Professors-at-Large Program keynote public talk. Cosponsored by the Dept. of Microbiology and Immunology and the Dept. of Molecular Biology and Genetics.

Abstract: This talk focuses on the way the T-cell program emerges from primitive blood cell precursors with both myeloid and lymphoid cell developmental potentials. The migration of the multipotent precursors from bone marrow to the thymus makes T-cell development possible, as the thymic environment delivers strong Notch pathway signals to the precursor cells until they relinquish alternative potentials and undergo commitment to the T-cell lineage. The availability of powerful in vitro culture systems to mimic the thymus have enabled studies leading to a deep molecular analysis of the underlying mechanisms. The cells start with a multipotent precursor chromatin epigenomic state that persists with minimal change as the T cell transcriptional program begins, even though inherited closed chromatin measurably holds back the onset of expression of critical T-cell genes. However, as commitment is triggered, thousands of changes occur coordinately across the genome, involving both opening and closing of chromatin sites, activation of new T-cell regulatory genes, and silencing of progenitor-state regulatory genes. The basis for these epigenome and transcriptional changes is the dynamic regulation of the T-cell and progenitor-cell transcription factors. The activity of the transcription factors can modify chromatin states, but is sharply dependent on dose-dependent, combinatorial binding with partner factors. The ensemble of factors that guide T cell development is activated under the aegis of continued activity of a different, multipotent progenitor gene regulatory network circuit, which involves the same regulatory genes that can act as oncogenes if not completely and accurately silenced. Their activity means that T cell development begins with a competition between two partially opposing gene network circuits within individual cell nuclei that is resolved only when the cells undergo commitment. Recent work sheds light on previously inaccessible events at the very onset of T cell lineage specification.

Dr. Ellen Rothenberg is a Distinguished Professor of Biology at the California Institute of Technology and an internationally recognized molecular immunologist whose research explains how blood stem cells develop into T-cells of the immune system. Her work reveals how networks of genes, regulatory proteins, and cellular signals work together—often at the level of individual cells—to guide critical developmental decisions that shape immune function.