Aaron Whiteley

  • Assistant Professor
Address

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

  • 2024 Burroughs Wellcome Fund PATH Award – Burroughs Wellcome Fund
  • 2023 ASM Award for Early Career Basic Research – American Society for Microbiology
  • 2023 Pew Scholars Program in the Biomedical Sciences Award – Pew Charitable Trusts
  • 2023 Mentor Award Honorable Mention – Undergraduate Research Opportunities Program, CU Boulder
  • 2022 NIH Director’s New Innovator Award (DP2) – National Institutes of Health (DP2AT012346)
  • 2022 Boettcher Investigator and Webb-Waring Biomedical Research Awardee – Boettcher Foundation
  • 2018 Outstanding Postdoctoral Fellow Award – Microbiology & Immunobiology, Harvard Medical School
  • 2017 Postdoctoral Fellowship – Jane Coffin Childs Memorial Fund for Medical Research
  • 2015 Richard and Mary Finkelstein Travel Grant and Young Investigator Oral Presentation – American Society for Microbiology, ASM General Meeting 2015
  • 2012 Graduate Research Fellowship Award – National 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. 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.

In mammals, detection of pathogenic bacteria and viruses starts with receptors of the innate immune system that sense microbe-derived chemical signals. 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 viruses that infect bacteria, phages.

The finding that bacterial antiphage genes are homologous to human antiviral genes 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 and highly tractable model system. Our lab is interested in identifying other elements of the human immune system that can be found in bacteria, understanding molecular mechanisms of phage/virus detection, and distilling these findings identify generalizable characteristics 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 goal of defeating human pathogens and cancers.

See my NCBI bibliography for a full and up-to-date list

  • Conte AN, Ridgeway SM, Ruchel ME, Kibby EM, Nagy TA, Whiteley AT. Phage detection by a bacterial NLR-related protein is mediated by DnaJ. bioRxiv. 2024 Jun 4;. doi: 10.1101/2024.06.04.597415. PubMed PMID: 38895412; PubMed Central PMCID: PMC11185742.
  • Ledvina HE, Whiteley AT. Conservation and similarity of bacterial and eukaryotic innate immunity. Nat Rev Microbiol. 2024 Jul;22(7):420-434. doi: 10.1038/s41579-024-01017-1. Epub 2024 Feb 28. Review. PubMed PMID: 38418927; PubMed Central PMCID: PMC11389603.
  • 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. Epub 2023 May 8. PubMed PMID: 37160116; PubMed Central PMCID: PMC10294775.
  • 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. Epub 2023 Feb 8. PubMed PMID: 36755092; PubMed Central PMCID: PMC10292035.