Assistant Professor Biochemistry
Protein evolution in viruses and immunity, SARS-CoV-2, HIV, Zoonosis, Molecular evolution
We study molecular evolution at the host-virus interface, where specific protein-protein interactions drive rapid evolution of viral surface proteins, the host receptors that they bind, and the antibodies that inhibit these interactions. We leverage a combination of evolutionary, biochemical, and virological approaches to connect the functional effects of amino acid mutations to their biophysical origins and evolutionary consequences. Our basic studies of protein evolution shed light on important phenotypes in virology and immunity, from viral zoonosis to the development of broadly protective antibodies. We are building off current projects on SARS-CoV-2 and HIV to develop a broad research program studying diverse emerging viruses of public health interest.
References (Selected Publications)
- Starr, TN*,†, SK Zepeda*, AC Walls, AJ Greaney, D Veesler†, JD Bloom†. ACE2 binding is an ancestral and evolvable trait of sarbecoviruses. Nature 603:913-918 (2022). Link.
- Starr, TN*,†, AJ Greaney*, WW Hannon, AN Loes, K Hauser, JR Dillen, E Ferri, A Ghez Farrell, B Dadonaite, M McCallum, KA Matreyek, D Corti, D Veesler, G Snell, JD Bloom. Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution. Science early access (2022) doi: 10.1126/science.abo7896. Link.
- Starr, TN*, N Czudnochowski*, Z Liu* … D Corti, JD Bloom, G Snell. SARS-CoV-2 RBD antibodies that maximize breadth and resistance to viral escape. Nature 597:97-102 (2021). Link.
- Starr, TN*, AJ Greaney*, A Addetia, WW Hannon, MC Choudhary, AS Dingens, JZ Li, JD Bloom. Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. Science 371(6531):850-854 (2021). Link.
- Greaney, AJ*, TN Starr*, P Gilchuk*, SJ Zost*, … JE Crowe Jr, JD Bloom. Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition. Cell Host & Microbe29(1):44-57 (2021). Link.
- Starr, TN*, AJ Greaney*, … NP King, D Veesler, JD Bloom. Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding. Cell182(5):1295-1310 (2020). Link.
- Starr, TN*, JM Flynn*, P Mishra*, DNA Bolon, JW Thornton. Pervasive contingency and irreversibility in a billion years of Hsp90 evolution. PNAS, 115(17):4453-4458 (2018). Link.
- Starr, TN, LK Picton, JW Thornton. Alternative evolutionary histories in the sequence space of an ancient protein. Nature, 549:409-413 (2017). Link.
- Starr, TN, JW Thornton. Epistasis in protein evolution. Protein Science, 25(7):1204-1218 (2016). Link.