This Mentored Clinical Scientist Development Award will provide Dr. James M. Roger the support necessary for him to continue his training from that of a recent dental school graduate (DOS, 2008) towards a PhD in Immunology with the long term goal of pursuing an academic career. Dr. Roger's training will be under the guidance of co-mentors, Dr. Ignacio Sanz and Dr. James E. Melvin. Having begun the didactic and preliminary experiments of his graduate thesis project, he will focus his efforts on studying cytokine production by B cells in Sjogren's Syndrome (SS). The hallmark symptoms of glandular destruction leading to dry mouth and dry eye are associated with inflammation and infiltrating lymphocytes. Recent studies in B cell depletion therapy have suggested a central pathogenic role for B cells in autoimmunity as well as further observations that B cells contribute to disease progression by """"""""antibody independent"""""""" means such as cytokine production. B cells in human SS as well as mouse models have been observed to produce a diverse array of cytokines such as, IL-10, IL-6, TNF- Ipha, and IFN- amma. While the observation that B cells are capable of producing a variety of cytokines both locally in the gland and systemically in the blood in SS is intriguing, a systematic approach to dissect the function of these cytokine producing B cells is proposed to further define their effector function. Dr. Roger will test the hypothesis that cytokine-producing B cells contribute to SS through systemic inflammatory modulation and target-tissue influences in three specific aims.
Aim 1 : Characterization of the cytokines and cytokine-producing B cell populations in a local cohort of healthy subjects.
Aim 2 : Characterize the cytokines and cytokine-producing B cell populations in a local cohort of SS patients.
Aim 3 : Examine the involvement that infiltrating B cells play in the disease process in SS salivary glands. Public Health Relevance: Sjogren's Syndrome is one of the most common autoimmune diseases afflicting an estimated 1-4% of the US population and women to men in a ratio of 9:1. By characterizing the role of B cells in the SS versus the healthy patient, it may be possible to develop new and specific screening tools and treatments for SS in the future. Finally, this award will provide Dr. Roger the tools necessary to prepare more advanced grant submissions leading to a career in academic research.
|Newell, Kenneth A; Asare, Adam; Kirk, Allan D et al. (2010) Identification of a B cell signature associated with renal transplant tolerance in humans. J Clin Invest 120:1836-47|