The immune system is essential to our health, and yet its understanding is in its infancy. In particular, immune sensing and response, often the first steps in widely divergent systemic decisions, present key targets for manipulation and modeling. Indeed, in recent years study of these processes has yielded increasing abundance of quantitative data, along with the development of powerful theoretical and simulation methods.

Some of the aspects of the immune system I am interested in:

• T-cells have specialized receptors which when triggered, initiate a signaling cascade that results in a systemic decision whether to mount a full scale immune response or not. As such, the T-cell signaling cascade controls life and death decisions. Understanding and manipulating it is one of the major challenges of immunology. The reductionist approach to the T-cell receptor signaling cascade has mapped out the immensely complicated set of biochemical reactions, and several small-molecule inhibitory drugs have been developed to target different biochemical aspects of this signaling cascade. As physicists, it is tempting to classify these inhibitors into two families: those inhibiting the signal before its initial feedback amplification, and those inhibiting the signal after feedback. But does the biological reality agree with this view? Can a simple dynamical model explain the dichotomy, ignoring the complex biochemical details? The answer is yes to both questions. There is much yet to understand about T-cell response to immune stimulus and its systemic effects.
• Our bone marrow produces billions of blood cells every day, maintaining steady state with respect to natural cell death, while affording quick response in case certain cell types need to be replenished due to disease or trauma. This fascinating and tightly regulated system begins with stem cells that divide and undergo a series of differentiation steps to more and more specialized cell types. What is the structure of this differentiation graph? What are the cellular fluxes and bottlenecks? Surprisingly little is known, and much of this knowledge was obtained in inflammatory conditions or using elaborate genetic manipulations.

Related work:

• Dichotomy of cellular inhibition by small-molecule inhibitors revealed by single-cell analysis
• Universality of biochemical feedback and its application to immune cells
• Critical slowing down in biochemical networks with feedback
• Cell-to-cell information at a feedback-induced bifurcation point
• Multicellular sensing at a feedback-induced critical point
• Quantifying the Dynamics of Hematopoiesis by In Vivo IdU Pulse‐Chase, Mass Cytometry, and Mathematical Modeling
• Lymphocytic division clocked up by Myc
• Modeling of cytometry data in logarithmic space: when is a bimodal distribution not bimodal?