Medved, Jelena (Luckey)
Broadly defined, my research goal is to understand the mechanism behind alloimmunization to red blood cells (RBC). Out of 5 million blood transfusions that occur annually in the US, immune response against transfused RBC develops in 2-4% of patients, which means that 100,000 – 200,000 of patients are in lethal danger. To minimize the risk or fatality, antibody screens are performed on all patients, but finding compatible blood is time consuming and expensive. This is especially the case for patients who suffer from chronic diseases, such as sickle cell anemia, that require repeated transfusions. Identifying factors underlying RBC alloimmunization and understanding the role they play will help us find ways to prevent these life-threatening situations.
Based on the published observation that memory B cells and memory T cells share a portion of the gene expression profile with that of hematopoietic stem cells, our lab has generated both constitutive and conditional knockouts of a transcription factor whose expression is enriched in all three self-renewing populations – Pou6f1. Pou6f1 has also been shown to be enriched in T follicular helper (Tfh) cells, specialized providers of T cell help to B cells, that are essential for development of high-affinity antibodies and memory B cells. Preliminary results from our lab indicate that Pou6f1 deficient mice generate fewer anti-RBC antibodies in response to transfusion. Since transcription factors are critical for directing cell behavior and fate choice, Pou6f1 is an excellent candidate as a regulator of anti-RBC antibody production, differentiation of Tfh cells from naïve CD4 cells, as well as responses of memory cells.