Albert Siryaporn
University of California-Irvine, CA·Microbiology & Immunology
Skin, soft tissue, and wound infections remain hard to treat, especially in people with chronic diabetes, and the bacteria most often found in non-healing wounds have become resistant to many antibiotics. Rather than searching for an entirely new drug, this work takes its design cues from how the human immune system kills bacteria, aiming to build a new class of antimicrobials from components the body already uses.
- Fields
Microbiology & Immunology
Biophysics
Pharmacology
- Topics
histones
neutrophil extracellular traps
cathelicidin
- Grants
- 1 known grant, through Jun 2027
What they work on
- Identify combinations of human histones with the antimicrobial peptide LL-37 and other membrane- or cell wall-targeting antimicrobials that produce the strongest killing and synergy against Staphylococcus aureus, Pseudomonas aeruginosa, and communities of skin bacteria in vitro.
- Test whether engineering features of histones found in neutrophil extracellular traps, specifically chemical modification by citrullination and tethering to DNA fibers, augments their antimicrobial activity.
- Determine the mechanism of synergy by which pore-forming antimicrobials allow histones to enter bacteria and interfere with gene expression, producing irreversible killing.
- Validate the most potent histone and antimicrobial combinations in a standardized mouse skin infection model, including a diabetic mouse model reflecting impaired antimicrobial defenses.
More about the research
The focus is neutrophil extracellular traps, webs that white blood cells cast out to catch and kill microbes. These traps contain histones, proteins that normally package DNA inside our own cells, and the antimicrobial peptide LL-37, also called cathelicidin. Earlier work from this lab and a collaborating lab reported that histones and LL-37 together are far more lethal than either alone: LL-37 punches pores in the bacterial membrane, letting histones get inside the bacterium and interfere with gene expression, which kills the cell irreversibly. The project aims to understand this synergy and exploit it. One line of work will search for combinations of human histones with LL-37 and other membrane- or cell wall-targeting antimicrobials that produce the strongest killing, testing them against Staphylococcus aureus, Pseudomonas aeruginosa, and mixed communities of skin bacteria in the laboratory. A second line will try to boost activity by mimicking how histones are modified inside the traps, specifically through citrullination, a chemical change to the protein, and by tethering histones to DNA fibers as they are in real traps. The most promising combinations will then be tested in a standardized mouse skin infection model, including a diabetic mouse model to address wound infection in patients whose antimicrobial defenses are impaired.
Why it matters
Staphylococcus aureus and Pseudomonas aeruginosa dominate chronic non-healing wounds and include multi-drug resistant strains such as MRSA, leaving few treatment options, especially for patients with diabetes. Combinations of human histones with membrane-targeting antimicrobials could become a new class of therapeutics for skin, soft tissue, and wound infections, and the work would provide mechanistic insight plus pre-clinical data needed before such treatments could be developed.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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Jessica Brinkworth
University of Illinois Urbana-Champaign, IL·Microbiology & Immunology
Test whether neutrophils, front-line germ-killing white blood cells, from larger mammals kill Escherichia coli less effectively per cell, comparing direct killing and phagocytosis across 20 terrestrial species spanning 7 orders of magnitude in body mass.
The school
University of California-Irvine: 46 labs on PI Pages, $645M a year on research, 524 research doctorates a year.
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