We are proud to announce that Mike Kuhns, PhD, Assistant Professor, was recently awarded a $1.5 million 4-year R01 grant by the National Institute of Allergy and Infectious Diseases. Over the life of the grant, Dr. Kuhns and his lab personnel will be studying “Probing the mechanistic basis for T cell fate decisions.” The TCR-CD3 complex, CD4, and CD28 are vital checkpoint molecules that allow T cells to survey for antigens and activation induced molecules on the surfaces of antigen presenting cells (APCs). They then transfer this antigen- and APC-specific information to the T cell’s intracellular signaling apparatus. Ultimately, this information directs the T cell fate decisions that drive development, activation, differentiation, and the execution of effector functions. The fundamental importance of these molecules to immune surveillance and human health has resulted in several studies regarding their structure and function over the past 25+ years. As a result, much is now known about their individual structures, their interactions with their respective ligands in isolation, and the signaling cascades that result from these interactions. But, we have yet to determine how they fit and work together as components of the molecular machinery that drives T cell fate decisions and this has prevented us from understanding how this molecular machinery, as a whole, executes its functions. Further, this lack of knowledge has handicapped our ability to strategically target this molecular machinery with reagents designed to either enhance responses to vaccines, tumor, or pathogens, or to attenuate responses to transplants or auto-antigens. Our goal during this granting period is to deconstruct, understand, and ultimately manipulate the form and function of this complex macromolecular machine.
