School of Medicine
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C. Garrison Fathman
Professor of Medicine (Immunology and Rheumatology), Emeritus
Current Research and Scholarly InterestsMy lab of molecular and cellular immunology is interested in research in the general field of T cell activation and autoimmunity. We have identified and characterized a gene (GRAIL) that seems to control regulatory T cell (Treg) responsiveness by inhibiting the Treg IL-2 receptor desensitization. We have characterized a gene (Deaf1) that plays a major role in peripheral tolerance in T1D. Using PBC gene expression, we have provisionally identified a signature of risk and progression in T1D.
George D. Smith Professor of Molecular and Genetic Medicine and Professor of Pathology and of Genetics
Current Research and Scholarly InterestsWe study natural cellular mechanisms for adapting to genetic change. These include systems activated during normal development and those for detecting and responding to foreign or unwanted genetic activity. Underlying these studies are questions of how a cells can distinguish information as "self" versus "nonself" or "wanted" versus "unwanted".
Liu (Liao) Family Professor
Current Research and Scholarly InterestsThe microbiome carries out extraordinary feats of biology: it produces hundreds of molecules, many of which impact host physiology; modulates immune function potently and specifically; self-organizes biogeographically; and exhibits profound stability in the face of perturbations. Our lab studies the mechanisms of microbiome-host interactions. Our approach is based on two technologies we recently developed: a complex (119-member) defined gut community that serves as an analytically manageable but biologically relevant system for experimentation, and new genetic systems for common species from the microbiome. Using these systems, we investigate mechanisms at the community level and the strain level.
1) Community-level mechanisms. A typical gut microbiome consists of 200-250 bacterial species that span >6 orders of magnitude in relative abundance. As a system, these bacteria carry out extraordinary feats of metabolite consumption and production, elicit a variety of specific immune cell populations, self-organize geographically and metabolically, and exhibit profound resilience against a wide range of perturbations. Yet remarkably little is known about how the community functions as a system. We are exploring this by asking two broad questions: How do groups of organisms work together to influence immune function? What are the mechanisms that govern metabolism and ecology at the 100+ strain scale? Our goal is to learn rules that will enable us to design communities that solve specific therapeutic problems.
2) Strain-level mechanisms. Even though gut and skin colonists live in communities, individual strains can have an extraordinary impact on host biology. We focus on two broad (and partially overlapping) categories:
Immune modulation: Can we redirect colonist-specific T cells against an antigen of interest by expressing it on the surface of a bacterium? How do skin colonists induce high levels of Staphylococcus-specific antibodies in mice and humans?
Abundant microbiome-derived molecules: By constructing single-strain/single-gene knockouts in a complex defined community, we will ask: What are the effects of bacterially produced molecules on host metabolism and immunology? Can the molecular output of low-abundance organisms impact host physiology?
3) Cell and gene therapy. We have begun two new efforts in mammalian cell and gene therapies. First, we are developing methods that enable cell-type specific delivery of genome editing payloads in vivo. We are especially interested in delivery vehicles that are customizable and easy to manufacture. Second, we have begun a comprehensive genome mining effort with an emphasis on understudied or entirely novel enzyme systems with utility in mammalian genome editing.
Assistant Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)
BioDr. Matthew Frank, MD, PhD, is an Assistant Professor of Medicine in the Division of Blood and Marrow Transplantation and Cellular Therapy at Stanford University. Dr. Frank predominantly cares for patients with high-risk lymphoma and other blood cancers. He is a lead investigator of clinical trials evaluating the safety and effectiveness of cancer treatments called chimeric antigen receptor (CAR ) T therapy for patients with lymphomas and leukemias. Dr. Frank’s research focuses on developing methods to identify patients who are at high risk for relapse or developing side-effects after receiving CAR T therapy and to understand why these relapses and side-effects occur.