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In This Section
Michael Silverman, MD, PhD
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.
Bio
Dr. Silverman joined the faculty at CHOP in 2016 where his research program studies the long-term impacts of early-life interactions between commensal microbes and the developing immune system. His research accomplishments leverage knowledge of how these interactions with the immune system could prevent autoimmunity.
Genetic and Microbiota Impacts on T1D:
Demonstrated that major histocompatibility complex class II (MHCII) molecules prevent autoimmune diabetes by shaping the intestinal microbiota early in ontogeny, which, in turn, impacts the development of the immune system.
Signal Transduction in Mast Cells:
Demonstrated that the adaptor protein SLP-76 was essential for FceRI mediated allergic and anaphylactic responses through its interaction with the adaptor protein Gads leading to the formation of highly coordinated signaling complex at the cell membrane.
Pediatric Eastern Equine Encephalitis:
Investigated the natural history of eastern equine encephalitis and described the important association between the clinical prodrome and eventual outcome. This work describes the largest collection of pediatric EEE cases in the literature.
Dr. Silverman also works in collaboration with several CHOP researchers:
- Microbiome and selective IgA deficiency (collaboration with Sarah Henrickson)
- Early-life microbiome and Clostridium difficile infection (collaboration with Joe Zackular)
- Neonatal sepsis in Botswana (collaboration with Susan Coffin)
- MHCII antigen presentation and T1D (collaboration with Ike Eisenlohr)
- Human early-life microbiome and anti-commensal immune response (collaboration with Jeff Gerber)
Education and Training
BA, Cornell University, 1998
MD/PhD, University of Pennsylvania, Perelman School of Medicine (Immunology PhD), 2007
Pediatric Residency, Boston Children's Hospital, 2010
Pediatric Infectious Disease Fellowship, Boston Children's Hospital, 2013
Post-doctoral Fellowship, Harvard Medical School, 2016
Titles and Academic Titles
Assistant Professor of Pediatrics, Perelman School of Medicine, University of Pennsylvania
Attending Physician, Pediatric Infectious Disease, Children's Hospital of Philadelphia
Professional Memberships
American Academy of Pediatrics, 2007-
Pediatric Infectious Disease Society, 2010-
Infectious Disease Society of America, 2011-
Society of Mucosal Immunology, 2016-
American Association of Immunologists, 2018-
Professional Awards
Adolf J. Creskoff Prize for Research, University of Pennsylvania School of Medicine, 2006
The Fred Lovejoy Residency Research and Education Award, Boston Children's Hospital, 2009
Senior Resident Teaching Award, Boston Combined Residency Program, 2010
Graduation Speaker, Boston Children's Hospital, 2010
Fellow Teaching Award, Boston Combined Residency Program, 2011
Pediatric Infectious Disease Fellowship Award, Pediatric Infectious Disease Society, 2011
JDRF Advanced Post-doctoral Fellowship Award, 2013
K08 NIAID, Clinical Science Mentored Career Development Award, 2015
JDRF Career Development Award, 2020
Publication Highlights
PubMed:
Denu L, Lubin JB, Douglas B, Tuluc F, Silverman MA. Diet-induced microbial autofluorescence confounds flow cytometry of ex vivo isolated fecal microbes. Eur J Immunol. 2019 Aug; PubMed PMID: 31429932
Tanca A, Palomba A, Fraumene C, Manghina V, Silverman MA, Uzzau S. Clostridial butyrate biosynthesis enzymes are significantly depleted in the gut microbiota of nonobese diabetic mice. mSphere. 2018 Oct; 3(5). 3:e00492-18. PubMed PMID 30355671
Silverman M, Kua L, Tanca A, Pala M, Palomba A, Tanes C, Bittinger K, Uzzau S, Benoist C, Mathis D. Protective major histocompatibility complex allele prevents type 1 diabetes by shaping the intestinal microbiota early in ontogeny. Proc Natl Acad Sci USA. 2017 Sep; 114(36):9671-9676. PubMed PMID: 28831005; PubMed Central PMCID: PMC5594701
Silverman MA, Shoag J, Wu J, Koretzky GA. Disruption of SLP-76 interaction with Gads inhibits dynamic clustering of SLP-76 and FcepsilonRI signaling in mast cells. Mol Cell Biol. 2006 Mar; 26(5):1826-38. PubMed PMID: 16479002; PubMed Central PMCID: PMC1430252
Koretzky GA, Abtahian F, Silverman MA. SLP76 and SLP65: complex regulation of signaling in lymphocytes and beyond. Nat Rev Immunol. 2006 Jan; 6(1):67-78. PubMed PMID: 16493428
Active Grants/Contracts
Dissecting the interplay of MHC/HLA loci, the microbiota and autoimmune diabetes
- NIH K08 AI114970-01
- 01/06/15-12/31/20
- The goal of this study is to explore interactions between diabetes-protective MHC/HLA molecules and intestinal microbiota.
- Silverman, Michael A (PI)
A pediatric microbial community to dissect host-commensal interaction in type 1 diabetes
- NIH R21
- 2020-2022
- The goal of this study is to use novel a gnotobiotic mouse colonized with a novel early life community of microbes to identify commensal microbes that prevent T1D.
- Silverman, Michael A (PI)
Leveraging humoral immunity to promote commensal microbial protection from T1D
- Juvenile Diabetes Research Foundation International (JDRF)
- 2020-2025
- The goal of this study is to use novel antibody based approaches to identify commensal microbes that prevent T1D.
- Silverman, Michael A (PI)
Discovery of small molecules that selectively suppress activation of diabetogenic CD4+ T cells
- Foerderer Award, CHOP
- Silverman, Michael A (collaborator)
Leveraging gnotobiotic mouse models of the early-life microbiome to dissect Salmonella pathogenesis in children
- CHOP Junior Faculty Pilot Award
- 2019-2020
- The goal of this project is to use a novel gnotobiotic mouse model system to determine the contribution of early life microbiota and immune system components for pediatric enteric infections.
- Silverman, Michael A (PI)