Joseph Larkin III

Associate Professor 

Description of Research

The basic goals of the immune system are to mediate effective defense against infectious microorganisms, and the elimination of defective/cancerous self tissues.  However immune system activation must be tightly regulated in order to prevent immune responses which could result in autoimmune disease, a process known as tolerance.  Regulatory T cells (Tregs), a subset of T lymphocytes, play a crucial role in tolerance by limiting immune system activation.  Numerous studies have shown that an absence of Tregs, or decrease in Treg function, can result in premature death or autoimmunity.  Conversely, because Tregs possess the capacity to inhibit immune responses, Tregs have also been implicated in the inability of the immune system to clear certain cancers.  Since Tregs can play a critical role in the prevention of autoimmunity and the prevention of cancer treatments, Treg effector function must be critically regulated.  However, to date, the mechanisms by which Tregs are controlled are not well understood.

My laboratory investigates the contribution of T lymphocyte subsets and functions in maintaining tolerance, with a specific emphasis on Tregs.  We have examined the involvement of Tregs in the prevention of a number of animal models of human disease including type 1 diabetes, lupus, and rheumatoid arthritis.  We are currently investigating mechanisms that control Treg function.  One such mechanism could be the suppressors of cytokine signaling family of intracellular proteins (SOCS).   SOCS proteins regulate cellular responsiveness to cytokines, which are proteins involved in cellular communication.  Although it is known that certain cytokines are essential for Treg survival and function, how SOCS proteins contribute to this process are not well understood.  One primary focus of our laboratory is to examine the interplay between Tregs and SOCS proteins. Learn more...

In addition to self tissues, our immune systems are also tolerant to the myriads of bacteria residing in our luminal spaces.  In the absence of appropriate tolerance mechanisms directed toward resident gut flora, immune system mediated diseases of the gut can arise.  As might be expected, tolerance to resident gut flora requires a dynamic interplay between Tregs and other T cell subsets.   However, the notion that resident gut flora can modulate immune system function raises an additional, more far reaching question.  Resident gut flora can be influenced by many environmental factors such as the food we eat, antibiotics that we take, or hygiene.  How changes in gut flora influence the immune system are poorly understood.  Moreover, it is poorly understood whether changes in gut flora can influence the onset of autoimmune disease.  Another focus of the lab is to determine whether changes in gut flora can modulate the onset of the autoimmune disease type 1 diabetes.

Teaching Interests
  • PCB 5235 - Immunology
  • PCB 4233 - Immunology
  • MCB 6355 - Microbial Defense

Joseph Larkin III