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Calvin Williams, MD, PhD

Calvin B. Williams, MD, PhD

Professor, Pediatrics and Microbiology & Immunology; Associate Dean of Research; Associate Director, Medical Scientist Training Program; Chief Scientific Officer, Children's Wisconsin Research Institute; Chief, Pediatric Rheumatology; Vice Chair, Research, Pediatrics

Contact Information

General Interests

T cell development, Regulatory T cell biology, Mucosal tolerance


MD and PhD, Biology and Medicine, University of California, Irvine, 1991

Leadership Positions

  • Chief Scientific Officer, Children's Research Institute
  • Professor of Pediatrics, Microbiology and Immunology
  • Section Chief, Pediatric Rheumatology

Research Interests


The broad, long-term objective of research in my laboratory is to establish the mechanisms that promote T cell development in the thymus and maintain T cell tolerance in the periphery. We place special emphasis on role of Foxp3 regulatory T (Treg) cells, and have developed a number of mouse models that are widely used to study Treg cell function. This body of work has contributed to our understanding of T cell receptor antagonism as potent mechanism of peripheral tolerance (1), the mechanisms of Treg cell-mediated suppression in models of inflammatory autoimmune disease (2), the role of Foxp3 in Treg cell development (3), and the identification of “induced” Treg (iTreg) cells as an essential regulatory subset required for mucosal tolerance (4). Current work is focused on discovering the mechanisms that control the inducible components of mucosal tolerance, including the iTreg-Th17 cell axis (Figure 1).


Figure 1. Model of Treg cell development. The nTreg cell population (green) develops as a distinct lineage in the thymus. In the periphery, TGF-b1 induces Tconv cells to become iTreg cells (red) or Th17 cells (purple). The peripheral Treg (pTreg) cell pool is therefore comprised of both iTreg and nTreg cells. IL-6 promotes production of Th17 cells while blocking iTreg cell formation. Smad3 promotes Foxp3 expression and stability. In some circumstances, iTreg cells are unstable and lose Foxp3 expression (ex-Foxp3+ iTreg or “ex-iTreg” cells, pink). These ex-iTreg cells may become Th1 (blue) or Th17 cells, or reacquire Foxp3 and cycle back into the iTreg pool. IL-10 produced by iTreg cells functions in an autocrine feedback loop to promote iTreg cell transcriptional and phenotypic stability. The activation of ex-iTreg cells and their migration from the mesenteric lymph nodes to the intestinal mucosa is also specifically prevented by iTreg cell produced IL-10. In Current work in the lab is divided into three Aims. In Aim 1, we will determine how the iTreg cell niche is created and maintained. In Aim 2 we will examine the fate of ex-iTreg cells, and in Aim 3 we will show that iTreg cell produced IL-10 has both shared and unique roles. in gastrointestinal tolerance.