Michael S. Diamond, M.D., Ph.D.
Pathology and Immunology
Molecular Microbiology and Microbial Pathogenesis Program
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. Recently, we have begun to study other emerging viral infections including Zika and Chikungunya 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.
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
Lazear HM, Daniels BP, Pinto AK, Huang AC, Vick SC, Doyle SE, Gale Jr M, Klein RS, and Diamond MS. 2015. Interferon-l restricts West Nile virus neuroinvasion by tightening the blood-brain barrier. Science Translational Medicine. 22;7(284):284ra59: PMCID: PMC4435724.
Miner JJ, Daniels BP, Shrestha B, Proenca-Modena JL, Lew ED, Lazear HM, Gorman MJ, Lemke G, Klein RS, Diamond MS. 2015. 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.
Lazear HM, Govero J, Smith AM, Platt DJ, Fernandez E, Miner JJ, Diamond MS. 2016. A Mouse Model of Zika Virus Pathogenesis. Cell Host and Microbe. 19(5):720-30. PMCID: PMC4866885.
Miner JJ, Cao B, Govero J, Smith AM, Fernandez E, Cabrera OH, Garber C, Noll M, Klein RS, Noguchi KK, Mysorekar IU, Diamond MS. 2016. Zika virus infection during pregnancy in mice causes placental damage and fetal demise. Cell. 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. 2016. A CRISPR screen defines a signal peptide processing pathway required by flaviviruses. Nature. 535(7610):164-168. PMCID: PMC4945490.
Zhao H, Fernandez E, Dowd KA, Speer SD, Platt DJ, Gorman MJ, Govero J, Nelson CA, Pierson TC, Diamond MS, Fremont DH. 2016. Structural Basis of Zika Virus-Specific Antibody Protection. Cell. 2016 Jul 26. pii: S0092-8674(16)30927-8. PMCID: PMC4983199.
Last Updated: 8/23/2016 1:31:44 PM