Assistant Professor of Biological Engineering
“Our research combines protein engineering, structural biology, and bioinformatics to understand and manipulate immune-cell recognition and signaling. We are working to better understand the natural immune response, create novel immune tools and treatments, and develop methods to better study and engineer diverse repertoires of molecules.”
Michael Birnbaum is an assistant professor of biological engineering at MIT. He received his bachelor's degree in chemical and physical biology from Harvard University and his PhD from Stanford University in 2014. There, he worked under K. Christopher Garcia, and studied the molecular mechanisms of T cell receptor recognition, cross-reactivity, and activation. After postdoctoral work in Carla Shatz’s group at Stanford supported by a Helen Hay Whitney Postdoctoral Fellowship, Professor Birnbaum joined MIT and the Koch Institute in 2016. During his tenure at the Koch Institute, Birnbaum has received the AACR-TESARO Career Development Award for Immuno-oncology Research, a Packard Fellowship in Science and Engineering, a Pew-Stewart Scholarschip for Cancer Research, a V Scholar Grant from the Jimmy V Foundation, and the Michelson Prize for Human Immunology and Vaccine Research. In October 2020, he received the National Institutes of Health (NIH) New Innovators Award. He serves as an advisor for Cogen Therapeutics.
The immune system leverages immense molecular diversity in the T, B, and NK cell receptor repertoires to distinguish between normal cells and cells altered by infection or cancer. This molecular diversity often makes understanding exactly what is recognized during the course of an immune response extremely challenging. As a result, efforts to study antigen recognition have often been limited to working with model antigens.
The Birnbaum group focuses on understanding and manipulating immune responses in the context of cancer and infection. They use a variety of strategies and techniques including protein biochemistry, protein engineering, sequencing, and bioinformatics to 1) identify and sequence immune receptors of interest, 2) decode what the immune response is ‘seeing’ in response to cancer or infection, 3) answer questions about how the immune system composition and dynamics affect the success or failure of an immune response, and 4) develop ways to rewire the signaling and recognition of immune responses. This type of systematic, unbiased examination of T cell recognition has, until recently, been extremely difficult. With this information, Professor Birnbaum and his team will be able to rationally engineer new methods to more specifically mount a potent immune response.
For more information about Professor Birnbaum’s research, please visit the Birnbaum lab webpage.
D'Souza MP, Adams E, Altman JD, Birnbaum ME, Boggiano C, Casorati G, Chien YH, Conley A, Eckle SBG, Früh K, Gondré-Lewis T, Hassan N, Huang H, Jayashankar L, Kasmar AG, Kunwar N, Lavelle J, Lewinsohn DM, Moody B, Picker L, Ramachandra L, Shastri N, Parham P, McMichael AJ, Yewdell JW. 2019. Casting a wider net: Immunosurveillance by nonclassical MHC molecules. PLoS Pathog. 15(2):e1007567. doi: 10.1371/journal.ppat.1007567.
Clancy-Thompson E, Devlin CA, Tyler PM, Servos MM, Ali LR, Ventre KS, Bhuiyan MA, Bruck PT, Birnbaum ME, Dougan SK. 2018. Altered Binding of Tumor Antigenic Peptides to MHC Class I Affects CD8+ T Cell-Effector Responses. Cancer Immunol Res. 6(12):1524-1536. doi: 10.1158/2326-6066.CIR-18-0348.
Holec PV, Berleant J, Bathe M, Birnbaum ME. 2018. A Bayesian framework for high-throughput T cell receptor pairing. Bioinformatics. doi: 10.1093/bioinformatics/bty801.
Rappazzo CG, Birnbaum ME. 2017. Tuning up T-cell receptors. Nat Biotechnol 35: 1145–1146.
Adams JJ, Narayanan S, Birnbaum ME, Sidhu SS, Blevins SJ, Gee MH, Sibener LV, Baker BM, Kranz DM, Garcia KC. 2016. Structural interplay between germline interactions and adaptive recognition determines the bandwidth of TCR-peptide-MHC cross-reactivity. Nat Immunol 17: 87–94.
ME, Mendoza JL, Sethi DK, Dong S, Glanville J, Dobbins J, Ozkan E, Davis MM, Wucherpfennig KW, Garcia KC. 2014. Deconstructing the peptide-MHC specificity of T cell recognition. Cell 157: 1073–1087.
Birnbaum ME, Berry R, Hsiao Y-S, Chen Z, Shingu-Vazquez MA, Yu X, Waghray D, Fischer S, McCluskey J, Rossjohn J, et al. 2014. Molecular architecture of the αβ T cell receptor-CD3 complex. Proc Natl Acad Sci USA 111: 17576–17581.
Birnbaum ME, Dong S, Garcia KC. 2012. Diversity-oriented approaches for interrogating T-cell receptor repertoire, ligand recognition, and function. Immunol Rev 250: 82–101.
Lupardus PJ, Birnbaum ME, Garcia KC. 2010. Molecular basis for shared cytokine recognition revealed in the structure of an unusually high affinity complex between IL-13 and IL-13Ralpha2. Structure 18: 332–342.