Hubert M. Tse, Ph.D.

Tse-2Assistant Professor of Microbiology



Address: 1825 University Blvd
Shelby Building, 1202
UAB
Birmingham, AL 35294
Telephone: 205-934-7037
FAX: 205-996-5220
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.



Members of the Laboratory
Publications

 

__________________________________________________________


Education


B.S.
(Biochemistry), Virginia Polytechnic Institute and State University, Blacksburg, VA
Ph.D. (Microbiology and Immunology), University of Colorado Health Sciences Center, Denver, CO


Research Interests


Type 1 diabetes (T1D) is an autoimmune-mediated disease resulting in the destruction of insulin-secreting pancreatic beta cells.  Adaptive immune maturation and the induction of an efficient T cell effector response requires three signals mediated by antigen-presenting cell and naïve T cell interactions: signal 1 (T cell receptor – MHC), signal 2 (co-stimulatory molecules), and signal 3 (reactive oxygen species and pro-inflammatory cytokines).  T cell activation in the absence of a pro-inflammatory third signal prevents the maturation of CD8+ T cells to gain cytolytic effector function and CD4+ T cells are unable to clonally expand or provide help for B cells to undergo isotype class switching.  The focus of my research involves signal 3 inhibition by targeting the innate immune response and signaling pathways that are responsible for reactive oxygen species (ROS) and pro-inflammatory cytokine synthesis by macrophages and dendritic cells with a metalloporphyrin-based catalytic antioxidant.  Prophylactic use of catalytic antioxidants are very efficient in generating antigen-specific hyporesponsiveness in vitro and in vivo by specifically targeting pro-inflammatory third signal generation and preventing the maturation and effector response of antigen-specific CD4+ and CD8+ T cells such as IFN-g synthesis and CTL effector molecules (perforin, granzyme B, and LAMP-1), respectively.  A detailed understanding of how redox modulation of innate immune-derived pro-inflammatory signal 3 generation and synergism with adaptive immune maturation will help in the design of more efficient immunotherapeutics for the treatment and prevention of T1D.


In an effort to corroborate the importance of ROS-dependent signaling in T1D, we have generated a murine model to further dissect the importance of pro-inflammatory third signal synthesis in autoreactive T cell activation.  While T lymphocytes (both CD4+ and CD8+ T cells) in insulitic infiltrates are likely the final effectors, activated macrophages in the preclinical infiltrates release high concentrations of ROS that are efficient in destroying co-cultured islets in vitro, yet the role of ROS as initiators and effectors in T1D is not clear.  A dominant negative p47phox (Ncf1m1J) mutation was introduced into the non-obese diabetic (NOD) mouse, a murine model for studying Type 1 diabetes.  The Ncf1m1J mutation prevented NADPH oxidase complex assembly, activity, and the inhibition of superoxide synthesis.  Homozygous NOD.Ncf1m1J mice do not develop spontaneous diabetes and are also resistant to adoptive transfer of diabetes with the diabetogenic BDC-2.5 T cell clone.  The resistance in spontaneous and adoptive transfer of diabetes was due to the absence of a sufficient innate immune-derived pro-inflammatory third signal that prevented the maturation and effector response of antigen-specific T cells.  Currently, I seek to understand how this mutation prevents the onset of spontaneous diabetes as well as the importance of superoxide in autoreactive T cell activation in Type 1 diabetes.