Office: JSCBB B221
Lab: JSCBB B255
PhD: Infectious Diseases and Immunity; Advisor: Dr. Daniel Portnoy. University of California Berkeley, 2010-2016
Postdoctoral Fellow: Microbiology; Advisors: Dr. John Mekalanos and Dr. Philip Kranzusch. Harvard Medical School, 2016-2019
Areas of Expertise
Bacteriology, Bioinformatics & computational biology, Cell signaling, Electron cryo-microscopy (cryo-EM), Genetics & chemical biology, Innate immunity, Nucleic acids, Infectious disease, Proteins & enzymology, Structural biology, Virology
Awards and Honors
How does the immune system detect a pathogen?
Our research group is broadly interested in how bacteria and viruses interact with, and often subvert, their host’s immune system. An infection can be viewed like a race. The host immune system has to detect an invading pathogen and respond, while pathogens like bacteria and viruses must evade detection and replicate. Who wins that race determines the outcome of disease.
Host–pathogen dynamics are shaped by the exchange of chemical signals between invaders and their victims (the host). In mammals, detection of pathogenic bacteria and viruses starts with receptors of the innate immune system that sense microbe-derived chemicals. Innate immune signaling activates the rest of the immune system to sterilize the infection. Identification of ligands (chemical signals) that activate the innate immune system has led to a better understanding of vaccines and the design of novel adjuvants. What’s more, some of these chemicals activate the immune system to fight cancer.
Our lab studies the innate immune system, the microbe-derived ligands important for immune activation, and general bacterial pathogenesis. We are particularly focused on immune pathways that use nucleotide second messengers to amplify signaling. One of the most exciting characteristics of these pathways is that they are found in both animal and bacterial cells. The same molecular machinery that allows eukaryotes to respond to DNA viruses (called the cGAS-STING pathway), is also found in bacteria. cGAS-like enzymes in bacteria are important for defense against to phages. These findings provide a highly tractable and rapid model system for studying the cGAS-STING pathway.
The finding of antiviral genes from bacteria that are homologous to antiviral genes in humans has led to the unexpected hypothesis that early eukaryotes must have assimilated and repurposed bacterial phage defense genes. This new paradigm in evolution of the immune system establishes bacterium-phage interactions as a relevant model system. Further, our lab is interested in identifying other elements of the human immune system that can be found in bacteria, understanding molecular mechanisms of phage detection, and distilling these findings identify generalizable aspects of immune systems.
The ultimate goal of our work is to better understand human immune signaling and inform the development of therapeutics, contributing to the worldwide goal of defeating human pathogens and cancers.
See my NCBI bibliography for a full and up-to-date list
- Kibby EM, Conte AN, Burroughs AM, Nagy TA, Vargas JA, Whalen LA, Aravind L, Whiteley AT. Bacterial NLR-related proteins protect against phage. Cell. 2023 May 25;186(11):2410-2424.e18. doi: 10.1016/j.cell.2023.04.015. PMID: 37160116.
- Ledvina HE*, Ye Q*, Gu Y, Sullivan AE, Quan Y, Lau RK, Zhou H, Corbett KD†, Whiteley AT†. (*equal contribution, †co-cor. author) An E1–E2 fusion protein primes antiviral immune signalling in bacteria. Nature. 2023 Apr;616(7956):319-325. doi: 10.1038/s41586-022-05647-4. PMID: 36755092.
- Whiteley AT, Eaglesham JB, de Oliveira Mann CC, Morehouse BR, Lowey B, Nieminen EA, Danilchanka O, King DS, Lee ASY, Mekalanos JJ*, Kranzusch PJ*. (*co-cor. author) Bacterial cGAS-like enzymes synthesize diverse nucleotide signals. Nature. 2019 Mar;567(7747):194-199. PMC6544370.
- Zhou W*, Whiteley AT*, de Oliveira Mann CC, Morehouse BR, Nowak RP, Fischer ES, Gray NS, Mekalanos JJ, Kranzusch PJ. (*equal contribution) Structure of the Human cGAS-DNA Complex Reveals Enhanced Control of Immune Surveillance. Cell. 2018 Jul 12;174(2):300-311.e11. PMC6084792.