David A. Hunstad, M.D.
Professor
Pediatrics
Infectious Diseases
Molecular Microbiology
Molecular Microbiology and Microbial Pathogenesis Program
314-286-2710
314-286-2874
314 286-2778
314-286-2895
6th Floor, McDonnell Pediatric Research Building
dhunstad@wustl.edu
http://research.peds.wustl.edu//labs/Hunstad_David_A
@dhunstad17
bacterial pathogenesis, Escherichia coli, host-pathogen interactions, innate immunity, novel therapeutics, urinary tract infection, kidney, pyelonephritis, sex differences
Sex differences, virulence mechanisms, and novel therapeutics in E. coli urinary tract infection
Research Abstract:
Work in the Hunstad lab focuses on the interactions of pathogenic bacteria with their hosts, using Gram-negative UTI as our primary model. We elucidate mechanisms by which pathogens modulate host innate responses, as well as host and bacterial influences on establishment of infection in the kidney (pyelonephritis).
Our primary goal is to discover novel targets for interventions that will prevent and treat bacterial infections of the urinary tract, gastrointestinal tract, and central nervous system. Along these lines, we are leveraging recent discoveries in UTI pathogenesis to design nanoparticle-based therapies for prevention of acute and recurrent UTI. Our newer mouse models of UTI permit first-ever preclinical studies of sex differences in UTI pathogenesis, as well as robust modeling of ascending renal abscess formation, resolution, and fibrosis.
Selected Publications:
Olson PD, McLellan LK, Hreha TN, Liu A, Briden KE, Hruska KA, Hunstad DA. Androgen exposure potentiates formation of intratubular communities and renal abscesses by Escherichia coli. Kidney Int 2018; 94: 502-513. PMC6109434
Olson PD, McLellan LK, Liu A, Briden KE, Tiemann KM, Daugherty AL, Hruska KA, Hunstad DA. Renal scar formation and kidney function following antibiotic-treated murine pyelonephritis. Dis Model Mech 2017; 10: 1371-1379. PMC5719254
Olson PD, Hruska KA, Hunstad DA. Androgens enhance male UTI severity in a new murine model. J Am Soc Nephrol 2016; 27: 1625-1634. PMC4884108
Loughman JA, Yarbrough ML, Tiemann KM, Hunstad DA. Local generation of kynurenines mediates inhibition of neutrophil chemotaxis by uropathogenic Escherichia coli. Infect Immun 2016; 84: 1176-1183. PMC4807489
Danka ES, Hunstad DA. Cathelicidin augments epithelial receptivity and pathogenesis in experimental Escherichia coli cystitis. J Infect Dis 2015; 211: 1164-1173. PMC4366604
Wagers PO, Tiemann KM, Shelton KL, Kofron WG, Panzner MJ, Wooley KL, Youngs WJ, Hunstad DA. Imidazolium salts as small-molecule urinary bladder exfoliants in a murine model. Antimicrob Agents Chemother 2015; 59: 5494-5502. PMC4538537
Lim YH, Tiemann KM, Heo GS, Wagers PO, Rezenom YH, Zhang S, Zhang F, Youngs WJ, Hunstad DA,* Wooley KL.* Preparation and in vitro antimicrobial activity of silver-bearing degradable polymeric nanoparticles of polyphosphoester-block-poly(L-lactide). ACS Nano 2015; 9: 1995-2008. PMC4455953
Lau ME, Danka ES, Tiemann KM, Hunstad DA. Bacterial lysis liberates the neutrophil migration suppressor YbcL from the periplasm of uropathogenic Escherichia coli. Infect Immun 2014; 82: 4921-4930. PMC4249291
Lau ME, Loughman JA, Hunstad DA. YbcL of uropathogenic Escherichia coli suppresses transepithelial neutrophil migration. Infect Immun 2012; 80: 4123-4132. PMC3497442
Loughman JA, Hunstad DA. Induction of indoleamine 2,3-dioxygenase by uropathogenic bacteria attenuates innate responses to epithelial infection. J Infect Dis 2012; 205: 1830-1839. PMC3415894
Last Updated: 3/1/2019 3:19:30 PM
E. coli (green) occupying a renal tubule engaged by neutrophils (red).