Hu’s research at UAB will focus on how to induce a primary antibody response like a memory one. “The humoral immune response is one of the two effector arms of the immune system,” explains Hu. “Studies have shown that CD4⁺ T follicular helper (Tfh) cells are essential for long-lived, high affinity antibody responses. Yet the complex regulation that determines the initial development of Tfh cells, their developmental progression in germinal centers (GC), and their fates after an immune response dissolves, is still not fully understood. Recently, my research has shown that transcription factor Foxp1 is a rate-limiting and essential negative regulator of Tfh cell differentiation, drastically affecting GC and antibody responses (Nat. Immunol. 2014).”

 “Usually your initial immune antibody response to an infectious agent takes about a week, and is relatively weak.” Hu says. “Now we have found an important regulatory step that could allow us to induce antibody responses more faster-acting and effective. And in the other way around, we may also be able to significantly dampen the antibody responses that are unwanted in some cases of autoimmune diseases such as lupus.”

Hu’s laboratory is also working to find a way to activate T cells under immunosuppressive circumstance. “Much of our understanding of molecular mechanisms regulating immune responses is centered on pathways and processes that promote cell activation, division and differentiation,” says Hu. “My research has already demonstrated that cell-intrinsic signaling pathways are required to maintain mature T cells in a quiescent state (Nat. Immunol. 2011). If these pathways are disrupted, resting T cells become aberrantly activated even in the absence of antigen challenge. My next step is to identify regulatory genes and pathways that actively restrain T cell activation, and define the roles of such negative regulatory pathways in controlling T cell quiescence, effector responses, memory maintenance, and tumor immunology.”