Randy R. Brutkiewicz, PhD

The Brutkiewicz laboratory studies immune evasion by viruses and tumors, the regulation of antigen presentation by various signal transduction pathways, and the role of innate and adaptive immune responses in CNS injuries and disorders.

In our laboratory, we study the CD1d and MR1 molecules, cell surface glycoproteins that are structurally related to major histocompatibility complex (MHC) class I molecules.  These molecules present lipid antigens or microbially-derived vitamin B metabolites to subpopulations of innate T cells called NKT and MAIT cells, respectively.  Efforts have focused on how signal transduction pathways can regulate antigen presentation in both innate (i.e., CD1d and MR1) and adaptive (e.g., MHC class I & II) immune responses.  We have found that CD1d-mediated antigen presentation is reciprocally-regulated by the mitogen-activated protein kinases (MAPK), p38 and ERK1/2.  This MAPK dichotomy is very evident following a virus infection of antigen presenting cells.  Further, we have recently reported that the protein kinase C δ pathway is very critical in the control of antigen presentation by both CD1d and MHC class II (but not MHC class I) molecules.  Increasing our understanding of signal transduction pathway control of antigen presentation will be of great help in the development of more effective vaccines against viruses and very useful in the treatment of various hematopoietic tumors, in which the reciprocal regulation of antigen presentation by MAPK is also observed.  Ongoing studies are analyzing additional mechanisms by which some tumors can evade this arm of the host's innate antitumor defenses, including those signal transduction pathways that play an important role in such activity.

Most recently, we have added studies of CNS injuries (e.g., spinal cord injury and TBI) and neurodegenerative diseases (e.g., Alzheimer's disease) and the contribution of the immune system in helping or harming the host's healing process.