After an immunology postdoctoral fellowship at Scripps Research, Saphire joined the faculty in the department of immunology as an assistant professor in 2003. She was promoted to associate professor in 2008 and full professor in 2012.[2] In 2019, joined the faculty at the La Jolla Institute for Immunology.[5]
Saphire solved the first structure of the entire human IgG.[6] The hexameric array predicted the assembly by which IgG could recruit C1q and launch the complement cascade,[7] which Saphire confirmed by obtaining the cryoEM structure of the C1q-IgG complex and hexameric IgG preparations.
Saphire is best known for her research on Ebola virus and other causes of viral hemorrhagic fever.[5] She was the first to discover the structure of the Ebola virus surface glycoprotein[8] and predicted that the Ebola virus receptor was located in the endosome rather than on the cell surface. Later, she showed that the Ebola virus VP40matrix protein can fold into multiple distinct structures.[3] In 2024, Saphire used in situ cryo-electron tomography to illuminate Ebola virus replication factories inside living cells revealing a hitherto unresolved third and outer layer of the nucleoprotein.[9] Her laboratory has also discovered the structure of the glycoproteins of Sudan virus, Marburg virus, Bundibugyo virus, Lassa virus and LCMV.[10] On field work in West Africa, she followed rodents to study how they spread viruses such as Ebola and Lassa.[5] Saphire attracted national media attention in 2014 when she launched a crowdfunding appeal to raise funds for equipment to assist in research to fight Ebola virus.[5][11]
In recent work, Saphire determined the cryo-electron microscopy structure of the measles virus fusion protein in complex with an antibody and determined that the antibody can trap the fusion protein in an intermediate state, thus halting fusion.[12]
Saphire directs the Viral Hemorrhagic Fever Immunotherapeutic Consortium (VIC)[10] and is a strong advocate for strategic collaborations to rapidly develop treatments for Ebola and other severe threats.[13] In 2020, Saphire was named director of the Coronavirus Immunotherapy Consortium (CoVIC), an international effort to evaluate human antibodies against the novel coronavirus, SARS-CoV-2.[14][15] Her lab also co-led research into COVID-19 mutations with scientists at the Los Alamos National Laboratory.[16] Saphire is also spearheading "America's SHIELD:Strategic Herpesvirus Immune Evasion and Latency Defense"[17] as part of ARPA-H's Antigens Predicted for Broad Viral Efficacy through Computational Experimentation (APECx) program.
In 2021, Saphire was appointed president and CEO of La Jolla Institute for Immunology. She succeeded Dr. Mitchell Kronenberg, who had served as institute president since 2003. Saphire is the institute's fifth president and is the first woman to serve in that role.[1]
