Katherine Radek
  • Assistant Professor
  • Surgical Research
  • Microbiology and Immunology
Research Keywords
  • Wound Healing
  • Infectious Diseases/Agents
Research Summary

Interest: Influence of stress and cholinergic signaling on innate immune function, infection and wound healing

  1. Research in the Radek laboratory focuses on how both physiologic and psychological stress influence cutaneous antimicrobial peptide (AMP) and Toll-like receptor signaling in burn and wound injury through activation of acetylcholine nicotinic receptors (nAChR). Antimicrobial peptide (AMP) production is critical for cutaneous innate immune homeostasis. Keratinocytes possess a non-neuronal cholinergic system comprised of acetylcholine (ACh) and acetylcholine nicotinic (nAChR) and muscarinic receptors. We previously determined that systemic cholinergic activation via psychological stress in mice diminished epidermal AMP expression, which was restored by topical application of nAChR antagonists. In parallel, we observed an increased susceptibility to bacterial infection, supporting clinical observations that stress promotes or exacerbates many skin disorders associated with AMP dysregulation. However, it is unknown whether this response is due to non-neuronal keratinocyte regulation of AMPs by ACh. We are investigating how excess or prolonged non-neuronal nAChR activation in the epidermis may promote AMP dysregulation and subsequent infection or inflammatory disease progression.
  2. S. aureus skin infections have become an enormous public health problem in the US. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)infections are on the rise and occur in patients without any known immunodeficiencies, with estimates of recurrence ranging from 10%-24%. A more defined understanding of the host immune response against S. aureus infection in the skin is essential to help develop urgently needed novel treatment regimens. Microbial susceptibility is due, in part, to a reduction in the expression or activity of antimicrobial peptides . AMPs are key molecules of the innate immune system that help to balance the host response to injury or infection. Disrupting this tight balance via changes in AMP regulation can shift the balance to restrict the ability of the skin to combat infection or initiate detrimental inflammatory processes. Microbial receptors (i.e. Toll-like receptor-2 [TLR2]) and resident immune cells, such as activated T-helper (TH) cells, play a pivotal role in the activation of AMP responses required for S. aureus clearance. Interleukin-17 (IL-17) is mainly produced by a TH cell subset, TH 17 cells. IL-17 directly participates in cell-mediated host defense against extracellular bacterial infections, particularly S. aureus clearance, and has recently been suggested as is a master regulator of AMPs in keratinocytes. The Radek lab is interested in characterizing the IL-17-dependent AMP response to cutaneous MRSA infection in healthy or MRSA infected human skin samples.
  3. During infection, epithelial Toll-like Receptors (TLRs) detect microbial components to induce antimicrobial peptides (AMP). innate immune factors that are directly microbicidal and elicit immune responses. Recently,our collaborators identified a microbiota in the female bladder, and identified that a less diverse microbiota correlates with a higher risk for urinary tract infection (UTI). A major gap exists in our understanding of urinary tract AMP regulation,in health or during UTI. Our objective is to expand this area of clinical research to identify the pathological consequences related to shifts in the bladder microbiota, and mechanisms for urothelial AMP suppression. Our long-term goal is to identify mechanisms by which the bladder microbiota and nicotinic acetylcholine receptor (nAChR) activation influences TLR-dependent urothelial AMP responses, and relate these changes in bladder microbiota and urothelial AMP regulation to the causal treatment of UTIs.

Dynamic Role of Host Stress Responses in Modulating the Cutaneous Microbiome: Implications for Wound Healing and InfectionHolmes,C. J.; Plichta,J. K.; Gamelli,R. L.; Radek,K. A.Advances in wound care 2015 ;4(1):24-37

Episodic binge ethanol exposure impairs murine macrophage infiltration and delays wound closure by promoting defects in early innate immune responsesCurtis,B. J.; Hlavin,S.; Brubaker,A. L.; Kovacs,E. J.; Radek,K. A.Alcoholism, Clinical and Experimental Research 2014 ;38(5):1347-1355

Interplay between Bladder Microbiota and Urinary Antimicrobial Peptides: Mechanisms for Human Urinary Tract Infection Risk and Symptom SeverityNienhouse,V.; Gao,X.; Dong,Q.; Nelson,D. E.; Toh,E.; McKinley,K.; Schreckenberger,P.; Shibata,N.; Fok,C. S.; Mueller,E. R.; Brubaker,L.; Wolfe,A. J.; Radek,K. A.PLoS ONE 2014 ;9(12):e114185

Local Burn Injury Impairs Epithelial Permeability and Antimicrobial Peptide Barrier Function in Distal Unburned SkinPlichta,J. K.; Droho,S.; Curtis,B. J.; Patel,P.; Gamelli,R. L.; Radek,K. A.Critical care medicine 2014 ; ( ):

Interleukin-33 increases antibacterial defense by activation of inducible nitric oxide synthase in skinLi,C.; Li,H.; Jiang,Z.; Zhang,T.; Wang,Y.; Li,Z.; Wu,Y.; Ji,S.; Xiao,S.; Ryffel,B.; Radek,K. A.; Xia,Z.; Lai,Y.PLoS Pathogens 2014 ;10(2):e1003918

Cholinergic regulation of keratinocyte innate immunity and permeability barrier integrity: new perspectives in epidermal immunity and diseaseCurtis,B. J.; Radek,K. A.Journal of Investigative Dermatology 2012 ;132(1):28-42

Sugar-Coating Wound Repair: A Review of FGF-10 and Dermatan Sulfate in Wound Healing and Their Potential Application in Burn WoundsPlichta,J. K.; Radek,K. A.Journal of Burn Care & Research 2012 ;33(3):299-310

Alcohol exposure and mechanisms of tissue injury and repairJung,M. K.; Callaci,J. J.; Lauing,K. L.; Otis,J. S.; Radek,K. A.; Jones,M. K.; Kovacs,E. J.Alcoholism, Clinical and Experimental Research 2011 ;35(3):392-399

Antimicrobial anxiety: the impact of stress on antimicrobial immunityRadek,K. A.Journal of leukocyte biology 2010 ;88(2):263-277

Acute ethanol exposure disrupts VEGF receptor cell signaling in endothelial cells.Radek,K. A.; Kovacs,E. J.; Gallo,R. L.; DiPietro,L. A.American Journal of Physiology - Heart & Circulatory Physiology 2008 ;295(1):H174-84

Effects of acute ethanol exposure on the early inflammatory response after excisional injury.Fitzgerald,D. J.; Radek,K. A.; Chaar,M.; Faunce,D. E.; DiPietro,L. A.; Kovacs,E. J.Alcoholism: Clinical & Experimental Research 2007 ;31(2):317-323

Matrix proteolytic activity during wound healing: modulation by acute ethanol exposure.Radek,K. A.; Kovacs,E. J.; DiPietro,L. A.Alcoholism: Clinical & Experimental Research 2007 ;31(6):1045-1052

Acute ethanol exposure impairs angiogenesis and the proliferative phase of wound healing.Radek,K. A.; Matthies,A. M.; Burns,A. L.; Heinrich,S. A.; Kovacs,E. J.; Dipietro,L. A.American Journal of Physiology - Heart & Circulatory Physiology 2005 ;289(3):H1084-90

Novel function for vascular endothelial growth factor receptor-1 on epidermal keratinocytes.Wilgus,T. A.; Matthies,A. M.; Radek,K. A.; Dovi,J. V.; Burns,A. L.; Shankar,R.; DiPietro,L. A.American Journal of Pathology 2005 ;167(5):1257-1266

  • French
  • Dancing
  • Adventure Travels
  • Animal Shelter Volunteer
  • Astronomy
  • Rock Collecting