Katherine Radek, PhD

Katherine Radek, PhD

Associate Professor

Ph.D., Loyola University Chicago

Research in the Radek laboratory focuses on how both physiologic (i.e. alcohol exposure) and psychological stress (i.e. cholinergic axis) influence cutaneous antimicrobial peptide (AMP) and Toll-like receptor signaling in burn wound and excisional wound injury. Antimicrobial peptide (AMP) production is critical for cutaneous homeostasis and the response to injury and infection. 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. For our alcohol studies, we recently determined that binge ethanol-exposed mice exhibited delayed wound closure, decreased macrophage accumulation, and impaired production of MIP-1a in infected skin wounds compared to vehicle-treated mice. Furthermore, skin from ethanol-exposed mice demonstrated a reduction in the abundance of epidermal cathelicidin AMP and the epidermal protease responsible for AMP proteolytic processing, kallikrein 7 (KLK7). These findings indicate that alcohol exposure hinders several discrete components of the innate immune system, including phagocyte recruitment and production of chemokines/cytokines and AMPs. Collectively, these effects likely contribute to delayed wound closure and enhanced infection severity observed in intoxicated patients. We are investigating how excess or prolonged non-neuronal nAChR activation and oxidative stress in the epidermis may promote AMP dysregulation and subsequent wound healing defects. 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.

View a partial list of Dr. Radek's publications through the National Library of Medicine's PubMed online database.

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

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

Li,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.Interleukin-33 increases antibacterial defense by activation of inducible nitric oxide synthase in skin PLoS Pathogens 2014 ;10(2):e1003918

Nienhouse,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.Interplay between Bladder Microbiota and Urinary Antimicrobial Peptides: Mechanisms for Human Urinary Tract Infection Risk and Symptom Severity PLoS ONE 2014 ;9(12):e114185

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

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

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

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

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

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

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

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

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

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