Yeast Engineering Technology and Immunobiology Core
John Misasi, M.D.
Associate Research Physician
Staff Clinician
Chief, Yeast Engineering Technology and Immunobiology Core
Contact: For contact information, search the NIH Enterprise Directory.
Specialty(s): Infectious Disease, Pediatrics Provides direct clinical care to patients at NIH Clinical Center
Major Areas of Research
- Immune repertoire analysis
- Antibody discovery
- Antibody and immunogen engineering
- Antibody paratope and epitope mapping
- Antibody therapies
Program Description
The Biodefense Research Section’s Yeast Engineering Technology and Immunobiology Core (YETI) at the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center (VRC), is located on the main National Institutes of Health (NIH) campus in Bethesda, MD. YETI combines the tools of high-throughput next-generation sequencing and yeast display to improve immunogen binding, antibody breadth and to investigate humoral immunity following natural infections and vaccination.
The YETI Core has developed an integrated microfluidics-based single cell sequencing and yeast display pipeline that is used to investigate B cell repertoires, discover high-affinity antibodies against pathogens and to characterize the quality of immune responses following vaccination or natural infection by pathogens such as Ebola, Lassa, HIV, SARS-CoV-2, SARS-CoV-1, hMPV, PIV and RSV. In addition, we create and interrogate mutagenic libraries in order to expand the breadth and potency of antibodies and immunogens.
Biography
Education
M.D., 2002, SUNY Upstate Medical University, Syracuse, NY
B.S., 1996, Boston University, MA
After graduating from Boston University with a degree in Biomedical Engineering, Dr. Misasi received a medical degree from SUNY-Upstate Medical University and completed a Pediatrics residency at New York University. He later completed a fellowship in Pediatric Infectious Diseases and was an instructor at Boston Children’s Hospital. During this time, Dr. Misasi’s research focused on determining the mechanisms of virus entry and was a key member of the research team that discovered NPC1 was the cellular receptor for Ebola, Sudan and Marburg viruses.
In 2015, Dr. Misasi joined the NIH Vaccine Research Center (VRC) as a staff clinician in the Biodefense Research Section. His research has focused on humoral immune responses and antibody discovery following vaccination and infection to pathogens such as Ebola, Sudan, Marburg, RSV, HIV and SARS-CoV-2. In particular, he uses a variety of biophysical, virological assays and yeast display methods to determine the structural and functional mechanisms of antibody action. Dr. Misasi participated in the discovery and advanced development of monoclonal antibody mAb114 (ansuvimab/Ebanga), which was approved by the FDA for the treatment of Ebola virus disease in humans.
In 2020, Dr. Misasi was named Chief of the VRC Yeast Engineering Technology and Immunobiology Core. The core collaborates across the VRC and uses yeast display technologies to investigate immune repertoires, identify high affinity antibodies, map antibody binding and to engineer immunogens and antibodies for increased binding and breadth.
Selected Publications
Zhou T, Wang L, Misasi J, Pegu A, Zhang Y, Harris DR, Olia AS, Talana CA, Yang ES, Chen M, Choe M, Shi W, Teng IT, Creanga A, Jenkins C, Leung K, Liu T, Stancofski ED, Stephens T, Zhang B, Tsybovsky Y, Graham BS, Mascola JR, Sullivan NJ, Kwong PD. Structural basis for potent antibody neutralization of SARS-CoV-2 variants including B.1.1.529. Science. 2022 Apr 22;376(6591):eabn8897.
Wang L, Zhou T, Zhang Y, Yang ES, Schramm CA, Shi W, Pegu A, Oloniniyi OK, Henry AR, Darko S, Narpala SR, Hatcher C, Martinez DR, Tsybovsky Y, Phung E, Abiona OM, Antia A, Cale EM, Chang LA, Choe M, Corbett KS, Davis RL, DiPiazza AT, Gordon IJ, Hait SH, Hermanus T, Kgagudi P, Laboune F, Leung K, Liu T, Mason RD, Nazzari AF, Novik L, O'Connell S, O'Dell S, Olia AS, Schmidt SD, Stephens T, Stringham CD, Talana CA, Teng IT, Wagner DA, Widge AT, Zhang B, Roederer M, Ledgerwood JE, Ruckwardt TJ, Gaudinski MR, Moore PL, Doria-Rose NA, Baric RS, Graham BS, McDermott AB, Douek DC, Kwong PD, Mascola JR, Sullivan NJ, Misasi J. Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants. Science. 2021 Aug 13;373(6556):eabh1766.
Wang B, DeKosky BJ, Timm MR, Lee J, Normandin E, Misasi J, Kong R, McDaniel JR, Delidakis G, Leigh KE, Niezold T, Choi CW, Viox EG, Fahad A, Cagigi A, Ploquin A, Leung K, Yang ES, Kong WP, Voss WN, Schmidt AG, Moody MA, Ambrozak DR, Henry AR, Laboune F, Ledgerwood JE, Graham BS, Connors M, Douek DC, Sullivan NJ, Ellington AD, Mascola JR, Georgiou G. Functional interrogation and mining of natively paired human VH:VL antibody repertoires. Nat Biotechnol. 2018 Feb;36(2):152-155.
Misasi J, Gilman MS, Kanekiyo M, Gui M, Cagigi A, Mulangu S, Corti D, Ledgerwood JE, Lanzavecchia A, Cunningham J, Muyembe-Tamfun JJ, Baxa U, Graham BS, Xiang Y, Sullivan NJ, McLellan JS. Structural and molecular basis for Ebola virus neutralization by protective human antibodies. Science. 2016 Mar 18;351(6279):1343-6.
Corti D, Misasi J, Mulangu S, Stanley DA, Kanekiyo M, Wollen S, Ploquin A, Doria-Rose NA, Staupe RP, Bailey M, Shi W, Choe M, Marcus H, Thompson EA, Cagigi A, Silacci C, Fernandez-Rodriguez B, Perez L, Sallusto F, Vanzetta F, Agatic G, Cameroni E, Kisalu N, Gordon I, Ledgerwood JE, Mascola JR, Graham BS, Muyembe-Tamfun JJ, Trefry JC, Lanzavecchia A, Sullivan NJ. Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody. Science. 2016 Mar 18;351(6279):1339-42.
Côté M, Misasi J, Ren T, Bruchez A, Lee K, Filone CM, Hensley L, Li Q, Ory D, Chandran K, Cunningham J. Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection. Nature. 2011 Aug 24;477(7364):344-8.