Hubert M. Tse, PhD

Tse-HubertAssistant Professor

Dept. of Microbiology

Contact Information

Office Address: SHEL 1202
Phone: 934-7037
E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
Websites: UAB SOM Faculty Page


Virginia Tech, Blacksburg, VA
BSc, 1992

University of Colorado Health Sciences Center, Denver, CO
PhD, 1999

Post-Graduate Training:

Colorado State University, Ft. Collins, CO
Postdoctoral Fellow, Mycobacterial Research Laboratories, 1999-2001

University of Pittsburgh, Pittsburgh, PA
Postdoctoral Fellow, Diabetes Institute, 2001-2009

Research Description:

Type 1 diabetes is an autoimmune-mediated disease resulting in the destruction of insulin-secreting pancreatic b 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 ROS and pro-inflammatory cytokine synthesis by macrophages and dendritic cells.

The ability to modulate ROS-dependent signaling cascades necessary for inducing inflammation has provided therapeutic benefits in suppressing aberrant immune response in various pro-inflammatory disease processes such as Type 1 diabetes, endotoxic shock, amyotrophic lateral sclerosis, Rheumatoid Arthritis, Crohn’s disease, and chronic obstructive pulmonary disease.  A key innate immune response signaling pathway that is suppressed by redox modulation is the NF-kB pathway.  The NF-kB pathway is a vital signaling pathway for the activation of pro-inflammatory cytokines, chemokines, cellular proliferation, and mediators of apoptosis.  NF-kB activation is tightly regulated at the transcriptional and post-translational levels, since aberrant and hyper-activation of NF-kB-dependent pro-inflammatory mediators is detrimental.

My research in the past several years has identified a novel regulatory mechanism of NF-kB inhibition mediated by catalytic antioxidant treatment to modulate pro-inflammatory signal 3 synthesis.  Metalloporphyrin-based catalytic antioxidants in addition to scavenging a multitude of noxious reactive oxygen species and inhibiting innate immune-derived pro-inflammatory cytokine synthesis, exhibit a unique ability to inhibit redox-sensitive transcription factors such as NF-kB.  Catalytic antioxidants contain an inherent oxidoreductase activity that can oxidize a redox-sensitive amino acid (C62) in the NF-kB p50 DNA-binding subunit to inhibit DNA-binding.  C62 in the reduced state will enhance DNA-binding, but if oxidized, NF-kB p50 DNA-binding is impaired and NF-kB-dependent pro-inflammatory gene transcription is suppressed.  Interestingly, catalytic antioxidant treatment had no effect on IKKa/b phosphorylation, IkB-a phosphorylation, IkB-a degradation, or NF-kB nuclear translocation suggesting that the mechanism of action of this immunotherapeutic is highly specific and only affecting the ability of redox-sensitive transcription factors to bind DNA. 

Targeting the innate immune response by modulating the redox state as a means of suppressing the adaptive immune response may hold promise as a new avenue of immunotherapy since this strategy can be utilized in conjunction with antigen-specific treatment to efficiently decrease innate immune-derived pro-inflammatory mediators leading to ablation of antigen-responding T cell populations.  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 of inflammatory-mediated diseases.
In an effort to corroborate the importance of ROS-dependent signaling in Type 1 diabetes, we have generated a murine model to further dissect the importance of pro-inflammatory third signal synthesis in autoreactive T cell activation in Type 1 diabetes.  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.  In collaborative studies with Dr. Clayton Mathews at the University of Florida, 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 generates a premature stop codon resulting in a truncated p47phox protein that prevents 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 appears to be due to the absence of a sufficient innate immune-derived pro-inflammatory third signal since LPS-stimulated macrophages exhibited significant decreases in pro-inflammatory cytokines (TNF-a, IL-1b, IL-12 p70) 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.  The NOD.Ncf1m1J model is an ideal system to understand how ROS can modulate the autoimmune response in Type 1 diabetes.  This unique animal model overlaps with my research interest using antioxidant therapies and will synergize to confirm the efficacy of small molecule catalytic antioxidants as viable immunotherapeutics for modulating innate immune-derived signaling pathways during inflammatory-mediated diseases.


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