Joseph Larkin III

Assistant ProfessorLarkin

Department of Microbiology and Cell Science University of Florida

Ph.D. (2000) University of Florida,Department of Microbiology and Cell Science
Postdoctoral: The Wistar Institure/The University of Pennsylvania, Philadelphia, PA

Contact Information

352-392-6884
jlarkin3@ufl.edu

Teaching Interests

PCB 5235

PCB 4233

MCB6355

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.

Honors and Awards

  • 2013 New Treatments Award from Lupus Research Institute. Read more …
  • Richard L. Jones Outstanding New Faculty Research Award for 2012
  • 2009 BD Biosciences Research Grant Award Recipient 2009
  • The Association of Medical Laboratory Immunologists Travel Award Recipient 2006
  • Keystone Symposia Travel Award Recipient 2005.

Activities and Services

Professional Memberships

Member, Network of Minority Research Investigators 2007-present

  • NMRI Conference Planning Committee 2010

Member, The American Association of Immunologists 2008- present

  • AAI Minority Affairs Committee 2009-present

Member, University of Florida Alumni Association 2005-present

Service

Journal of Clinical and Cellular Immunology Editorial Board 2010- present

Selected Publications

SELECTED PEER REVIEWED PUBLICATIONS

Collins EC, Jager LD., Dabelic R., Benitez PA., Holdstein K., Lau KK., Haider MI., Johnson HM., and Larkin J 3rd (2011)Inhibition of SOCS-1-/- Lethal Autoinflammatory Disease Correlated to Enhanced Peripheral Foxp3+ Regulatory T cell Homeostasis. J. Immunol. 187(5): 2666-76.

Lau K., Benitez P., Ardissone A., Wilson T., Collins EL., Lorca G., Li N., Sankar D., Wasserfall C., Neu J., Atkinson MA., Shatz DA., Triplett EW., and Larkin J 3rd (2011) Inhibition of Type 1 Diabetes Correlated to a Lactobacillus johnsonii N6.2 Mediated Th17 Bias. J. Immunol. doi: 10.4049/jimmunol.1001864.

Jager LD., Dabelic R., Waiboci LW., Lau K., Haider SM., Ahmed CMI., Larkin J 3rd., David D., and Johnson HM. (2010) The Kinase Inhibitory Region of SOCS-1 is Sufficient to Inhibit T helper-17 Function in Experimental Allergic Encephalomyelitis. J. Neuroimmunolgy. doi: 10.1016/j.jneuroim.2010.018.

Valladares R., Sankar D., Li N., Williams E., Lai KK., Abdelgeliel AS., Gonzalez CF., Wasserfall CH., Larkin J 3rd., Schatz D., Atkinson MA., Triplett EW., Neu J., and Lorca GL (2010) Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats. PLoS One. 5(5):e10507.

BD, Fields ML., Nish SA., Larkin J 3rd, Caton AJ., and Erikson J (2008) Autoantibody production in lpr/lpr gld/gld mice reflects accumulation of CD4+ effector cells that are resistant to regulatory T cell activity. J Autoimmun. doi:10.1016/j.jaut2008.04.022.

Larkin J 3rd, Rankin AL., Picca CC., Riley MP., Jenks SA., Sant AJ., and Caton AJ. (2008) CD4+CD25+ regulatory T cell repertoire formation shaped by differential presentation of peptides from a self-antigen. J Immunol. 180(4):2149-57.

Rankin AL., Reed AJ., Oh S., Picca CC., Guay HM., Larkin J 3rd., Aitken MK., Panarey L., Koeberlein B., Lipsky P., Tomaszewski JE., Naji A., and Caton AJ. (2008) CD4+ T cells recognizing a single self-peptide expressed by APC’s induce spontaneous autoimmune arthritis.  J Immunol. 180(2): 833-41.

Guay HM., Larkin J 3rd, Picca CC., and Caton AJ. (2007) Spontaneous auto-reactive memory B cell formation driven by a high frequency of auto-reactive CD4+ T cells. J Immunol. 178(8):4793-802.

Larkin J 3rd, Picca CC., and Caton AJ. (2007) Activation of CD4+CD25+ regulatory T cell suppressor function by analogs of the selecting peptide.  Eur J Immunol. 37(1): 139-46.

Villarino AV., Larkin J 3rd, Saris CJM., Caton AJ., Lucas S., Wong T., deSauvage FJ., and Hunter CA. (2005) Positive and Negative Regulation of the IL-27 Receptor during Lymphoid Cell Activation.  J Immunol. 174(12): 7684-91.

Lerman MA., Larkin J 3rd, Cozzo C., Jordan MS., and Caton AJ. (2004) CD4+CD25+ regulatory T cell repertoire formation in response to varying expression of a neo-self antigen. J Immunol. 173(1): 236-44.

Cozzo C., Larkin J 3rd and Caton AJ. (2003) Cutting edge: self peptides drive the peripheral expansion of CD4+CD25+ regulatory T cells. J Immunol.  171(11):5678-82.

Larkin J 3rd., Subramaniam PS., Torres BA., and Johnson HM. (2001) Differential properties of two putative nuclear localization sequences found in the carboxyl-terminus of human IFN-gamma. Journal of Interferon & Cytokine Research. 21(6):341-8.

Subramaniam PS., Larkin J 3rd., Mujtaba MG., Walter MR., and Johnson HM. (2000) The COOH-terminal nuclear localization sequence of interferon gamma regulates STAT1 alpha nuclear translocation at an intracellular site. Journal of Cell Science. 113 ( Pt 15):2771-81.

Larkin J 3rd., Johnson HM., and Subramaniam PS. (2000) Differential nuclear localization of the IFNGR-1 and IFNGR-2 subunits of the IFN-gamma receptor complex following activation by IFN-gamma. Journal of Interferon & Cytokine Research. 20(6):565-76.

BOOK CHAPTERS AND REVIEWS

Cozzo C., Larkin J. 3rd., Boesteanu A., Lerman MA., Rankin AL., and Caton AJ. (2006) Role of TCR specificity in CD4+CD25+ regulatory T cell selection. Immunol Rev. 212:74-85.

Caton AJ., Cozzo C., Larkin J 3rd., Lerman MA., Boesteanu A., and Jordan MS. (2004) CD4+CD25+ Regulatory T cells Selection. Ann NY Acad Sci. 1029:101-14.

Johnson HM., Torres BA., Green MM., Szente BE., Siler KI., Larkin J 3rd., and Subramaniam PS. (1998) Hypothesis: ligand/receptor-assisted nuclear translocation of STATs. Proceedings of the Society for Experimental Biology & Medicine. 218(3):149-55

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