Michael S. Diamond, M.D., Ph.D.

Professor
Internal Medicine
Infectious Diseases
Molecular Microbiology
Pathology and Immunology

Molecular Microbiology and Microbial Pathogenesis Program
Immunology Program

  • 314-362-2842

  • 314-362-2847

  • 314-362-9230

  • 8051

  • 7220 McDonnell Pediatric Research Building

  • diamond@borcim.wustl.edu

  • http://id.wustl.edu/investigators.html?id=55

  • virology, microbial pathogenesis, immunology

  • Innate and Adaptive Host Immunity to Viral Infections

Research Abstract:

The research in the Diamond laboratory focuses on the interface between viral pathogenesis and the host immune response. For several years, we have been primarily focused on two globally important mosquito-borne human pathogens, West Nile virus and Dengue virus. Both are single-stranded positive-sense RNA viruses of the same genus (Flavivirus) that cause human disease worldwide.We also study other emerging viral infections including Zika, Chikungunya, Mayaro, Powassan, and Spondweni viruses as well as new bunyaviruses. We are interested in defining mechanisms of innate immune restriction and viral immune evasion, generating novel mouse models and understanding the epitope specificity of protective antibodies. In addition, studies also now focus on the use of high throughput CRISPR/Cas9 whole genome screens to identify host factors required for these viral infections.

Studies with viruses have focused on investigating their pathogenesis and the immune system response that controls infection. Using in vitro models of infection in primary neurons, macrophages, and dendtitic cells, we are studying the mechanisms by which viruses causes direct injury to specific target cell types, and how the host responds to limit viral replication. Using mouse models we have defined critical roles for interferon, novel interferon stimulated genes, antibody, complement, CD4+, and CD8+ cell in the control and eradication of flavivirus infection and have begun defining how the microbiome modulates these phenotypes. We also study the structural and molecular bases of antibody-mediated protection of flaviviruses and alphaviruses, with a goal of identifying broadly neutralizing antibodies and their respective epitopes.

Selected Publications:

Daffis S, Szretter K, Schriewer J, Li J, Yoon S, Erret J, Lin TY, Schneller S, Zust R, Dong H, Thiel V, Pierson TC, Buller RM, Gale Jr M, Shi PY, and Diamond MS. 2’O methylation of the viral mRNA cap evades host restriction by IFIT family memners. Nature 2010 18:452-456. PMCID: PMC3058805.

Cho H, Proll SC, Szretter KJ, Katze MG, Gale M Jr, Diamond MS. Differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive-stranded RNA viruses. Nature Medicine. 2013 Apr;19(4):458-64. doi: 10.1038/nm.3108. Epub 2013 Mar 3. PMCID: PMC3618596

Hyde JL, Gardner CL, Kimura T, White JP, Liu G, Trobaugh DW, Huang C, Tonelli M, Paessler S, Takeda K, Klimstra WB, Amarasinghe GK, Diamond MS. A viral RNA structural element alters host recognition of nonself RNA. Science. 2014 Feb 14;343(6172):783-7. PMID: 24482115

Miner JJ, Daniels BP, Shrestha B, Proenca-Modena JL, Lew ED, Lazear HM, Gorman MJ, Lemke G, Klein RS, Diamond MS. The TAM receptor Mertk protects against neuroinvasive viral infection by maintaining blood-brain barrier integrity. Nature Medicine. 2015 Dec;21(12):1464-72. PMCID: PMC4674389

Fox JM, Long F, Edeling MA, Lin H, van Duijl-Richter MK, Fong RH, Kahle KM, Smit JM, Jin J, Simmons G, Doranz BJ, Crowe JE Jr, Fremont DH, Rossmann MG, Diamond MS. 2015. Broadly Neutralizing Alphavirus Antibodies Bind an Epitope on E2 and Inhibit Entry and Egress. Cell. 2015 Nov 19;163(5):1095-107. PMCID: PMC4659373.

Miner JJ, Cao B, Govero J, Smith AM, Fernandez E, Cabrera OH, Garber C, Noll M, Klein RS, Noguchi KK, Mysorekar IU, Diamond MS. Zika virus infection during pregnancy in mice causes placental damage and fetal demise. Cell. 2016. 165(5):1081-91. PMCID: PMC4874881.

Zhang R, Miner JJ, Gorman M, Rausch K, Ramage H, White JP, Zhang P, Fernandez E, Zhang Q, Dowd K, Pierson TC, Cherry S, Diamond MS.. A CRISPR screen defines a signal peptide processing pathway required by flaviviruses. Nature. 2016. 535(7610):164-168. PMCID: PMC4945490.

Richner JM, Himansu S, Dowd KA, Butler SL, Salazar V, Fox JM, Julander JG, Tang WW, Shresta S, Pierson TC, Ciaramella G, Diamond MS. Modified mRNA Vaccines Protect against Zika Virus Infection. Cell. 2017. Mar 9;168(6):1114-1125

Richner JM, Jagger BW, Shan C, Fontes CR, Dowd KA, Cao B, Himansu S, Caine EA, Nunes BTD, Medeiros DBA, Muruato AE, Foreman BM, Luo H, Wang T, Barrett AD, Weaver SC, Vasconcelos PFC, Rossi SL, Ciaramella G, Mysorekar IU, Pierson TC, Shi PY, Diamond MS. Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease. Cell. 2017. Jul 13;170(2):273-283

Zhang R, Kim AS, Fox JM, Nair S, Basore K, Klimstra WB, Rimkunas R, Fong RH, Lin H, Poddar S, Crowe JE Jr, Doranz BJ, Fremont DH, Diamond MS. Mxra8 is a receptor for multiple arthritogenic alphaviruses. Nature. 2018 May;557(7706):570-574. PMCID: PMC5970976.

Last Updated: 8/22/2018 10:46:45 AM

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