Biography

Dr. Walker is an Assistant Professor in the Department of Microbiology and Molecular Genetics at UTHealth Houston’s McGovern Medical School. Dr. Walker joined the department in 2019 after completing her postdoctoral training with Drs. Scott Hultgren and Michael Caparon at Washington University School of Medicine in St. Louis, MO.

Dr. Walker received her Ph.D. from the Department of Microbiology and Immunology at the University of Iowa after completing her doctoral thesis work.

Dr. Walker is a recipient of the Texas Rising STAR award (2019).

Education

Postdoctoral Fellow
Washington University School of Medicine
Ph.D. of Microbiology
The University of Iowa

Areas of Interest

Research Interests

The Walker lab is focused on understanding the host-pathogen interactions that dictate the onset, progression, and outcome of chronic infections. Our work uses infections of medical devices as a model for chronic disease. By defining the bacterial and host mechanisms the facilitate these recalcitrant infections, we seek to develop novel antibiotic sparing therapies that can effectively treat common and costly diseases. We use a multidisciplinary approach to blend the use of basic science, model systems, and patient samples to pursue the following questions:

 

  1. How do medical devices render people susceptible to infection?

Millions of medical devices are placed every year, and their use is expected to increase due to their efficacy at improving the length and quality of life. However, infection of medical devices is a common, dreaded complication. Our work indicates the device itself induces inflammation, which may prevent the host from mounting an effective response against pathogens, allowing them to cause disease. To define the host-pathogen-device interactions, we combine the use of model systems and patient samples to understand the inflammatory response to devices with and without infection to identify biomarkers that predict infection risk.

 

  1. What microbial virulence mechanisms increase disease severity and complications associated with medical device infections?

A broad range of microbes form chronic, recalcitrant medical device infections. Our group studies the different virulence mechanisms these microbes use to initiate infection, form recalcitrant communities, and progress to severe disease, including bacteremia and sepsis. Our work demonstrates that microbes, including staphylococci, Candida albicans, and Pseudomonas aeruginosa, attach to various host proteins that coat device surfaces and form recalcitrant biofilms that resist antibiotics. Additionally, these microbes use sensor regulatory systems to coordinate the response of virulence factors, including adhesins, enzymes, and proteases, to initiate and progress to severe infection. To define the microbial mechanisms that facilitate infection, we combine the use of microbial genetics and molecular microbiology to inform the development of novel antibiotic-sparing prevention and treatment strategies.

 

  1. How do genomic adaptions during long-term colonization impact persistence and pathogenic potential?

Many medical devices become asymptomatically colonized with pathogens. Chronic colonization increases the risk of developing symptomatic infection. Our genomic studies, including with S. aureus and Klebsiella pneumonia, indicate microbes acquire genomic changes that promote tissue tropism and increase pathogenic potential. We use a combination of epidemiology, genomics and bioinformatics, patient samples, and model systems to understand how bacteria evolve to persist asymptomatically long-term and adapt to become more pathogenic to help to guide the development of more effective prevention and treatment strategies.

 

  1. What therapeutic strategies are effective against medical device infections?

Medical device infections resist antibiotic therapy, and the current gold standard of treatment relies on device removal. Our group recently discovered that antibiotic pocket irrigants used during breast reconstruction post-mastectomy can enhance biofilm formation among clinically derived infection isolates and do not prevent infection in an animal model. We collaborate closely with physicians and use a combination of model systems patient and samples to understand how bacteria establish recalcitrant infections and translate these discoveries to guide prevention and/or treatment strategies.

Publications

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Walker JN, Pinkner CL, Lynch AJL, Ortbal S, Pinkner JS, Hultgren SJ, Myckatyn TM. Deposition of Host Matrix Proteins on Breast Implant Surfaces Facilitates Staphylococcus Epidermidis Biofilm Formation: In Vitro Analysis. Aesthet Surg J. 2020 Feb 17;40(3):281-295. doi: 10.1093/asj/sjz099. PubMed PMID: 30953053.

Walker JN, Hanson BM, Pinkner CL, Simar SR, Pinkner JS, Parikh R, Clemens MW, Hultgren SJ, Myckatyn TM. Insights into the Microbiome of Breast Implants and Periprosthetic Tissue in Breast Implant-Associated Anaplastic Large Cell Lymphoma. Sci Rep. 2019 Jul 17;9(1):10393. doi: 10.1038/s41598-019-46535-8. PubMed PMID: 31316085; PubMed Central PMCID: PMC6637124.

Walker JN, Poppler L, Pinkner CL, Hultgren SJ, Myckatyn T. Establishment and Characterization of Bacterial Infection of Breast Implants in a Murine Model. Aesthet Surg J. 2019 Jul 1;. doi: 10.1093/asj/sjz190. [Epub ahead of print] PubMed PMID: 31259380.

Walker JN, Pinkner CL, Pinkner JS, Hultgren SJ, Myckatyn TM. The Detection of Bacteria and Matrix Proteins on Clinically Benign and Pathologic Implants. Plast Reconstr Surg Glob Open. 2019 Feb;7(2):e2037. doi: 10.1097/GOX.0000000000002037. eCollection 2019 Feb. PubMed PMID: 30881821; PubMed Central PMCID: PMC6416121.

Walker JN, Flores-Mireles AL, Pinkner CL, Schreiber HL 4th, Joens MS, Park AM, Potretzke AM, Bauman TM, Pinkner JS, Fitzpatrick JAJ, Desai A, Caparon MG, Hultgren SJ. Catheterization alters bladder ecology to potentiate Staphylococcus aureus infection of the urinary tract. Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):E8721-E8730. doi: 10.1073/pnas.1707572114. Epub 2017 Sep 25. PubMed PMID: 28973850; PubMed Central PMCID: PMC5642702.

Flores-Mireles AL, Walker JN, Potretzke A, Schreiber HL 4th, Pinkner JS, Bauman TM, Park AM, Desai A, Hultgren SJ, Caparon MG. Antibody-Based Therapy for Enterococcal Catheter-Associated Urinary Tract Infections. mBio. 2016 Oct 25;7(5). doi: 10.1128/mBio.01653-16. PubMed PMID: 27795399; PubMed Central PMCID: PMC5080383.

Flores-Mireles AL, Walker JN, Bauman TM, Potretzke AM, Schreiber HL 4th, Park AM, Pinkner JS, Caparon MG, Hultgren SJ, Desai A. Fibrinogen Release and Deposition on Urinary Catheters Placed during Urological Procedures. J Urol. 2016 Aug;196(2):416-421. doi: 10.1016/j.juro.2016.01.100. Epub 2016 Jan 28. PubMed PMID: 26827873; PubMed Central PMCID: PMC4965327.

Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015 May;13(5):269-84. doi: 10.1038/nrmicro3432. Epub 2015 Apr 8. Review. PubMed PMID: 25853778; PubMed Central PMCID: PMC4457377.

Walker JN, Crosby HA, Spaulding AR, Salgado-Pabón W, Malone CL, Rosenthal CB, Schlievert PM, Boyd JM, Horswill AR. The Staphylococcus aureus ArlRS two-component system is a novel regulator of agglutination and pathogenesis. PLoS Pathog. 2013;9(12):e1003819. doi: 10.1371/journal.ppat.1003819. Epub 2013 Dec 19. PubMed PMID: 24367264; PubMed Central PMCID: PMC3868527.

Walker JN, Horswill AR. A coverslip-based technique for evaluating Staphylococcus aureus biofilm formation on human plasma. Front Cell Infect Microbiol. 2012;2:39. doi: 10.3389/fcimb.2012.00039. eCollection 2012. PubMed PMID: 22919630; PubMed Central PMCID: PMC3417647.

Lin LY, Tiemann KM, Li Y, Pinkner JS, Walker JN, Hultgren SJ, Hunstad DA, Wooley KL. Synthetic polymer nanoparticles conjugated with FimH(A) from E. coli pili to emulate the bacterial mode of epithelial internalization. J Am Chem Soc. 2012 Mar 7;134(9):3938-41. doi: 10.1021/ja2091917. Epub 2012 Feb 23. PubMed PMID: 22360307; PubMed Central PMCID: PMC3325780.

Chen SL, Hung CS, Pinkner JS, Walker JN, Cusumano CK, Li Z, Bouckaert J, Gordon JI, Hultgren SJ. Positive selection identifies an in vivo role for FimH during urinary tract infection in addition to mannose binding. Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22439-44. doi: 10.1073/pnas.0902179106. Epub 2009 Dec 16. PubMed PMID: 20018753; PubMed Central PMCID: PMC2794649.

Cegelski L, Pinkner JS, Hammer ND, Cusumano CK, Hung CS, Chorell E, Aberg V, Walker JN, Seed PC, Almqvist F, Chapman MR, Hultgren SJ. Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation. Nat Chem Biol. 2009 Dec;5(12):913-9. doi: 10.1038/nchembio.242. Epub 2009 Oct 25. PubMed PMID: 19915538; PubMed Central PMCID: PMC2838449.

Mysorekar IU, Isaacson-Schmid M, Walker JN, Mills JC, Hultgren SJ. Bone morphogenetic protein 4 signaling regulates epithelial renewal in the urinary tract in response to uropathogenic infection. Cell Host Microbe. 2009 May 8;5(5):463-75. doi: 10.1016/j.chom.2009.04.005. PubMed PMID: 19454350; PubMed Central PMCID: PMC2696285.

Henderson JP, Crowley JR, Pinkner JS, Walker JN, Tsukayama P, Stamm WE, Hooton TM, Hultgren SJ. Quantitative metabolomics reveals an epigenetic blueprint for iron acquisition in uropathogenic Escherichia coli. PLoS Pathog. 2009 Feb;5(2):e1000305. doi: 10.1371/journal.ppat.1000305. Epub 2009 Feb 20. PubMed PMID: 19229321; PubMed Central PMCID: PMC2637984.

Rosen DA, Pinkner JS, Jones JM, Walker JN, Clegg S, Hultgren SJ. Utilization of an intracellular bacterial community pathway in Klebsiella pneumoniae urinary tract infection and the effects of FimK on type 1 pilus expression. Infect Immun. 2008 Jul;76(7):3337-45. doi: 10.1128/IAI.00090-08. Epub 2008 Apr 14. PubMed PMID: 18411285; PubMed Central PMCID: PMC2446714.

Rosen DA, Pinkner JS, Walker JN, Elam JS, Jones JM, Hultgren SJ. Molecular variations in Klebsiella pneumoniae and Escherichia coli FimH affect function and pathogenesis in the urinary tract. Infect Immun. 2008 Jul;76(7):3346-56. doi: 10.1128/IAI.00340-08. Epub 2008 May 12. PubMed PMID: 18474655; PubMed Central PMCID: PMC2446687.

Hannan TJ, Mysorekar IU, Chen SL, Walker JN, Jones JM, Pinkner JS, Hultgren SJ, Seed PC. LeuX tRNA-dependent and -independent mechanisms of Escherichia coli pathogenesis in acute cystitis. Mol Microbiol. 2008 Jan;67(1):116-28. doi: 10.1111/j.1365-2958.2007.06025.x. Epub 2007 Nov 25. PubMed PMID: 18036139; PubMed Central PMCID: PMC3675907.