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  1. University of Arkansas for Medical Sciences
  2. College of Medicine
  3. Department of Microbiology and Immunology
  4. Faculty
  5. Primary Faculty
  6. Youssef Aachoui, Ph.D.

Youssef Aachoui, Ph.D.

Youssef Aachoui, Ph.D.

Assistant Professor 

Research Interest: Innate Immunity Defenses Against Intracellular Pathogens
Ph.D.: Indiana State University
Postdoctoral: University of North Carolina at Chapel Hill
Office: 501-686-7428
Lab: 501-320-7706
Fax: 501-686-5359
Email: YAachoui@uams.edu

Currently accepting new students

Research Description

The innate immune system serves as the body’s frontline defense, employing sophisticated mechanisms to detect and respond to microbial threats. Central to this response are inflammasomes—multiprotein complexes that sense pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and cellular stress signals. Assembled from sensor proteins, adaptors, and effector enzymes, inflammasomes activate inflammatory caspases, such as caspase-1 and caspase-11 (in mice) or caspase-4/5 (in humans), to amplify inflammation and trigger pyroptosis. In pyroptosis, these caspases cleave gasdermin D, a pore-forming protein that ruptures the cell membrane, releasing pro-inflammatory cytokines like IL-1β and IL-18 and lysing the cell. This programmed cell death is a strategic immune response, dismantling replication niches of intracellular pathogens to expose them to further immune attack. However, dysregulation of inflammasomes and regulated cell death can drive inflammatory disorders, where excessive or aberrant activation contributes to chronic inflammation and tissue damage. Our research explores this dual nature of inflammasomes—protective in immunity, yet potentially pathogenic when misregulated—shedding light on their fundamental roles in inflammation and innate immunity.

Our studies illuminate the broader significance of these mechanisms. Pyroptosis, by permeabilizing or lysing cells, disrupts cellular environments and function, a process we’ve observed with various bacterial models or inflammasome agonists. This reveals a core principle of how cell death alters cellular homeostasis, offering insights into the mechanics of immune activation and tissue response. We’ve also uncovered how pathogens, such as Shigella flexneri, deploy effectors like OspC3 to block caspase-11 activity, highlighting the dynamic interplay of molecular evasion and detection. Most recently, we found that inflammasome-driven neutrophil pyroptosis triggers extracellular traps (NETs), extending pyroptosis’s role to diverse immune contexts. Our current work involves studying the molecular mechanisms of regulated cell death, examining how cell type and inflammatory conditions shape these outcomes. By exploring variations across immune and non-immune cells, as well as the influence of acute versus chronic inflammation, we aim to decode the regulatory cues that fine-tune pyroptosis and related pathways. These insights deepen our understanding of fundamental cellular processes—cell death, inflammation, and immune activation

Team

Changhoon Oh , Ph.D.
Postdoctoral Fellow
Biomed1 Rm 520
Email: COh@uams.edu
Phone (lab): 501-320-7706
• M.S.: Seoul National University
• Ph.D.: Seoul National University
• Postdoctoral Training: UAMS

Todd J. Spears, M.S.
Graduate student
Email: tjspears@uams.edu
Phone (lab): 501-320-7706
• M.S. and B.S.: University of Louisiana at Monroe

Join Us

We are always looking for highly motivated individuals to join our group at all levels. If you have any questions prior to application, please contact Youssef via email at YAachoui@uams.edu.

Recent Publications

  • Oh C, Spears TJ, Aachoui Y. Inflammasome-mediated pyroptosis in defense against pathogenic bacteria. Immunol Rev. 2025 Jan;329(1):e13408. doi: 10.1111/imr.13408. Epub 2024 Oct 15. PMID: 39404258; PMCID: PMC11741929.
  • Oh C, Li L, Verma A, Reuven AD, Miao EA, Bliska JB, Aachoui Y. Neutrophil inflammasomes sense the subcellular delivery route of translocated bacterial effectors and toxins. Cell Rep. 2022 Nov 22;41(8):111688.
  • Oh C, Verma A, Hafeez M, Hogland B, Aachoui Y. Shigella OspC3 suppresses murine cytosolic LPS sensing. iScience. 2021 Jul 28;24(8):102910.
  • Kovacs SB, Oh C, Aachoui Y, Miao EA. Evaluating cytokine production by flow cytometry using brefeldin A in mice. STAR Protoc. 2020 Dec 30;2(1):100244.
  • Oh C, Verma A, Aachoui Y. Caspase-11 Non-canonical Inflammasomes in the Lung. Front Immunol. 2020 Aug 21;11:1895.
  • Kovacs SB, Oh C, Maltez VI, McGlaughon BD, Verma A, Miao EA, Aachoui Y. Neutrophil Caspase-11 Is Essential to Defend against a Cytosol-Invasive Bacterium. Cell Rep. 2020 Jul 28;32(4):107967.
  • Aachoui, Y., and Miao, E.A. (2016). Down with doublespeak: NAIP/NLRC4 inflammasomes get specific. The Journal of Experimental Medicine 213, 646
  • Aachoui, Y., Kajiwara, Y., Leaf, Irina A., Mao, D., Ting, Jenny P.Y., Coers, J., Aderem, A., Buxbaum, Joseph D., and Miao, E.A. (2015). Canonical Inflammasomes Drive IFN-β; to Prime Caspase-11 in Defense against a Cytosol-Invasive Bacterium. Cell Host & Microbe 18, 320-332.
  • Maltez, Vivien I., Tubbs, Alan L., Cook, Kevin D., Aachoui, Y., Falcone, E.L., Holland, Steven M., Whitmire, Jason K., and Miao, E. A. (2015). Inflammasomes Coordinate Pyroptosis and Natural Killer Cell Cytotoxicity to Clear Infection by a Ubiquitous Environmental Bacterium. Immunity 43, 987-997
  • Aachoui Y, Leaf IA, Hagar JA, Fontana MF, Campos CG, Zak DE, Tan MH, Cotter PA, Vance RE, Aderem A, Miao E.A. (2013). Caspase11 protects against bacteria that escape the vacuole. Science. 2013 Feb 22;339 (6122):9758.
  • Hagar JA, Powell DA, Aachoui Y, Ernst RK, Miao E.A.(2013). Cytoplasmic LPS activates caspase11: implications in TLR4independent endotoxic shock. Science. 2013 Sep 13;341(6151):12503.
  • Aachoui Y, Sagulenko V, Miao EA, Stacey KJ. (2013). Inflammasome mediated pyroptotic and apoptotic cell death, and defense against infection. Curr Opin Microbiol. 2013 Jun;16(3):31926.
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