The Students

The Big Picture

I study the molecular circuits that allow T cells to become competent to respond to infection while maintaining tolerance to self.

In an ever-changing world of pathogens, our immune systems must be able to reliably stave off a diverse barrage of possible infections. T cells — a central component of the adaptive immune system — rapidly respond to specific pathogens upon stimulation of their T cell receptor and provide long-lasting protection. This specificity emerges from random rearrangement of the genes that encode this receptor, giving rise to a space of over 10^15 possible receptor sequences and allowing us to react to practically any would-be invader. However, this stochastic process has the potential to generate specificity for self, which can result in autoimmunity if left unchecked. The immune system therefore faces a trade-off in selecting a T cell repertoire; it must maximize the range of pathogens that it can recognize while simultaneously minimizing the possibility of self-reactivity.

 

Originating in the bone marrow, T cells migrate to the thymus to mature. In this critical window, T cells develop into capable effectors, while those with specificity for self are inactivated. Employing a range of biochemical approaches combined with single-cell transcriptional and epigenetic profiling, I study the molecular circuits that allow T cells to become competent to respond to infection while maintaining tolerance to self, and I develop statistical tools that leverage the variation inherent in heterogeneous populations of cells to model these regulatory networks.