Aaron Whiteley 2022
Assistant Professor

Office: JSCBB B221
Lab: JSCBB B255

Education

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

  • 2023ÌýASM Award for Early Career Basic Research – American Society for Microbiology
  • 2023ÌýPew Scholars Program in the Biomedical SciencesÌýAwardÌý–ÌýPew Charitable Trusts
  • 2023ÌýMentor Award HonorableÌýMentionÌý–ÌýUndergraduate Research Opportunities Program, CU Boulder
  • 2022 NIH Director’s New InnovatorÌýAwardÌý(DP2)Ìý–ÌýNational Institutes of Health (DP2AT012346)
  • 2022ÌýBoettcher Investigator and Webb-Waring Biomedical Research AwardeeÌý–ÌýBoettcher Foundation
  • 2018 Outstanding Postdoctoral FellowÌýAwardÌý–ÌýMicrobiology & Immunobiology, Harvard Medical School
  • 2017 Postdoctoral FellowshipÌý–ÌýJane Coffin Childs Memorial Fund for Medical Research
  • 2015ÌýRichard and Mary Finkelstein Travel Grant and Young Investigator Oral Presentation –ÌýAmerican Society for Microbiology, ASM General Meeting 2015
  • 2012ÌýGraduate Research Fellowship AwardÌý–ÌýNational Science Foundation

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.ÌýAn infection can be viewed like a race. The host immune system has to detect an invading pathogen and respond, whileÌýpathogens 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). InÌýmammals, 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 ofÌýligands (chemical signals) that activate the innate immune system has led to a better understanding of vaccines and the design ofÌýnovel 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 bacterialÌýpathogenesis. We are particularly focused on immune pathways that use nucleotide second messengers to amplify signaling.ÌýOne of the most exciting characteristics of these pathways is that they are found in both animal and bacterial cells. The sameÌýmolecular machinery that allows eukaryotes to respond to DNA viruses (called the cGAS-STING pathway), is also found inÌýbacteria. cGAS-like enzymes in bacteria are important for defense against to phages. These findings provide a highly tractableÌýand 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 unexpectedÌýhypothesis that early eukaryotes must have assimilated and repurposed bacterial phage defense genes. This new paradigm inÌýevolution of the immune system establishes bacterium-phage interactions as a relevant model system. Further, our lab isÌýinterested in identifying other elements of the human immune system that can be found in bacteria, understanding molecularÌýmechanisms of phage detection, and distilling these findings identify generalizable aspects of immune systems.Ìý

The ultimate goal of our work is to better understand human immune signaling and inform the development of therapeutics,Ìýcontributing to the worldwide goal of defeating human pathogens and cancers.

³§±ð±ðÌýÌýfor 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.ÌýNature. 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.

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