Mihai Luchian Azoitei

Proteins are the building blocks of life and manipulating their function holds immense promise to uncover fundamental biological processes and develop novel therapeutics. Research in our group is focused on two synergistic areas that are critical for the development of broadly protective therapies against highly infectious pathogens. First, we aim to understand the intracellular signaling pathways that control B cell activation upon antigen encounter. We then combine these findings with insights from immunology, virology, and structural biology, to develop next-generation vaccines. Central to all our work is the ability to engineer proteins with novel functions using computational modeling, including recently developed Machine Learning approaches, and high throughput library screening.

To study B cell intracellular signaling, we engineer and utilize molecular tools (fluorescent biosensors and optogenetic probes) to visualize and control the activity of key signaling molecules in live cell microscopy experiments. Upon engagement of B cell receptors by antigens, multiple signaling pathways are triggered, and their activation levels and coordination in space and time are critical for B cell function. Our current focus is on mapping the activity of Rho GTPases and their main activators, the Dbl family of Guanine Exchange Factors (GEFs). These molecules control B cell morphodynamics and are critical for the formation of the immunological synapse. Because of their transient and dynamic nature, we aim to study GEF/GTPase signaling networks in living cells and to map their activity at the subcellular level and with sub-second kinetics.

For vaccine design, we employ a rational, structure-based approach that utilizes state-of-the-art computational protein design algorithms and high-throughput library screening. These techniques allow us to model the atomic details of protein structures and protein-protein interactions with high confidence and provide us with an experimental platform to rapidly screen millions of immunogen candidates. We are currently developing immunogens against HIV, coronaviruses, and influenza. The immunogens we engineer are characterized through collaborations with structural biologists, immunologists, and virologists.

Dr. Azoitei obtained a BA in Biochemistry and Computer Science from Middlebury College (Middlebury, Vermont) and a PhD in Biochemistry from the University of Washington (Seattle, WA), where he worked in the group of Dr. William Schief. He then completed postdoctoral studies in the lab of Dr. Klaus Hahn in the Department of Pharmacology at the University of North Carolina at Chapel Hill