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A postdoctoral position is immediately available at Children’s Hospital of Philadelphia to study host-microbiota interactions at mucosal surfaces, their impact on the early-life immune system and strategies for manipulating the microbiome and immune system to prevent autoimmune diabetes (T1D). This project is NIH funded and includes collaboration with the PennCHOP microbiome program.
Michael A. Silverman MD, PhD
The Silverman Lab aims to understand the mechanisms of immune system variation and to discover novel approaches to predict and prevent immune-mediated diseases, specifically the microbial and developmental factors that lead to T1D. Current research studies in the lab involve the genetic and microbiota impacts on T1D; pediatric gnotobiotic mouse model; and selective IgA deficiency (SIgAD).
Specifically, transgenic expression of the MHCII E molecule in NOD mice (Eα16/NOD)completely prevents T1D, mirroring dominant HLA protection from T1D in humans. Using these Eα16/NOD mice as a model of dominant genetic protection from T1D, the Silverman Lab demonstrated that protection from autoimmunity operates by the immune system shaping the early-life commensal microbiota. The lab’s ongoing project in this area aims to discover the mechanisms by which the host immune system impacts the development of commensal microbiota, and further, how commensal microbes educate the immune system to prevent autoimmunity. Modeling of HLA class II dominant protection from T1D supports the lab’s long-term goal of developing early-life microbiota-based therapies to prevent T1D in humans
The Silverman Lab has collaborated with Paul Planet, MD, PhD, attending physician in the Division of Infectious Diseases at CHOP, to generate the first gnotobiotic mouse model of the pediatric microbiome, which we call Pediatric Community or “PedsCom.” PedsCom is a consortium of 8 bacterial strains isolated from the intestine of pre-weaning diabetes-protected Eα16/NOD mice. These mice are unique and powerful tools to define the “rules of engagement” between the host and their commensal microbes.
Finally, the lab has recently defined the microbiome from pediatric patents lacking IgA. The team’s ongoing research aims to determine the mechanism for the increased incidence of autoimmune disease in patients with SIgAD. The lab developed a technique (mFLOW-SEQ) to tag microbes with a patient’s own serum IgG antibodies followed by metagenomic sequencing to define those microbes which activate, and in some cases, over-activate their immune systems.
Assistant Professor of Pediatrics
Dr. Silverman studies the fundamental aspects of early-life commensal microbes that influence immune system development and function. He discovered that the MHC-II E molecule prevents type 1 diabetes by shaping the intestinal microbiota early in life.