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Infectious Diseases

Principle Investigators

walker

Wendy Walker, Ph.D

Assistant Professor of the Center of Excellence in Infectious Diseases


Department of Biomedical Sciences
Center of Excellence in Infectious Diseases
Texas Tech University Health Sciences Center
5001 El Paso Drive, El Paso TX, Zip Code 79905
Phone: (915) 215-4268
wendy.walker@ttuhsc.edu


Research Interests

Innate immunity and sepsis

My laboratory investigates the interplay of innate immune pathways, physiological processes and sepsis. Sepsis is a disease that occurs when an infection leads to a systemic inflammatory response syndrome that is detrimental to the host. We utilize mouse models and cell culture to examine our hypotheses.

Pattern recognition receptors play a crucial role in host defense by inducing a rapid innate immune response early during infection or injury. These receptors recognize conserved motifs from the microbes themselves, and from damaged host tissues. For example, Toll-like Receptor 9 (TLR9) senses unmethylated CpG DNA resides in the endosomal compartment of cells. In the last several years, it has become clear that a second innate immune pathway recognizes DNA in the cytosol of cells, acting via the Stimulator of Interferon Genes and Interferon Regulatory Factor 3 signaling molecules. Inflammation triggered by the innate immune response usually helps the host combat infection. However, during sepsis an overwhelming systemic inflammatory response becomes harmful to the host. We are currently investigating whether the cytosolic DNA-sensing pathway plays a detrimental role in the context of sepsis.

Circadian rhythms are driven by a molecular clock that coordinates activity and other physiological processes to specific times during the 24 hour daily cycle. We found that circadian rhythms influence the innate immune response and sepsis. Mice exhibit a greater systemic inflammatory response and a more severe disease phenotype when sepsis in induced in the nighttime vs. the daytime. We are currently investigating how circadian rhythms control the innate immune response and sepsis.

HIV elite control and long-term nonprogression

HIV disease typically leads to progressive loss of CD4+ T cells, culminating in AIDS, unless antiretroviral therapy is administered. However, rare groups of HIV seropositive patients appear to have a natural ability to control the virus. HIV elite controllers maintain undetectable viral loads and resist progression to AIDS without taking medicine. Long-term nonprogressors maintain relatively high CD4+ T cell numbers and resist progression to AIDS without medicine, despite a detectable viral load. We are trying to elucidate how these patients naturally control the HIV virus, with the hope that this will reveal novel strategies for HIV treatment.


Education

Dr. Walker completed her BSc and PhD at the University of Edinburgh. She completed postdoctoral training at Imperial College London and Yale University. Subsequently, she worked as an Associate Research Scientist at Yale University. She joined the Center of Excellence in Infectious Diseases at TTUHSC El Paso as an Assistant Professor in January 2014.


Recent Publications

  1. Walker WE, Porteous DJ and Boyd AC. The effects of plasmid copy number and sequence context upon transfection efficiency. Journal of Controlled Release 2004, 94: 245-52.
  2. Tesar BM, Walker WE, Unternaehrer J, Joshi NS, Chandele A, Haynes L, Kaech S, and Goldstein DR. Murine myeloid dendritic cell dependent Toll Like Receptor immunity is preserved with aging. Aging Cell 2006, 5: 473-486.
  3. Walker WE, Nasr IW, Camirand G, Tesar BM, Booth CJ, and Goldstein DR. Absence of innate MyD88 signaling promotes inducible allograft acceptance. The Journal of Immunology 2006, 177:5307-5316.
  4. Walker WE and Goldstein DR. TLR pathways and innate responses to allografts.Current Opinions in Organ Transplantation 2007, 12: 5-9. (review article)
  5. Walker WE and Goldstein DR. Neonatal B cells suppress innate Toll-like receptor immune responses and modulate alloimmunity. The Journal of Immunology 2007, 179: 1700-1710.
  6. Shen, H, Walker WE, Tesar BM and Goldstein DR. Dual signaling of MyD88 and TRIF are critical for maximal TLR4-induced dendritic cell maturation The Journal of Immunology 2008, 181:1849-58.
  7. Stout-Delgado HW. Yang X, Walker WE, Tesar BM and Goldstein DR. Aging impairs IFN regulatory factor 7 up-regulation in plasmacytoid dendritic cells during TLR9 activation. The Journal of Immunology 2008, 181:6747-56.
  8. Tesar BM, Wei D, Shirali AC, Walker WE, Shen H and Goldstein DR. Aging augments IL-17 T cell alloimmune responses. The American Journal of Transplantation 2009, 9:54-63.
  9. Walker WE and Goldstein, DR. B cells are dispensable for neonatal transplant tolerance induction. Transplantation 2009, 88: 874-878.
  10. Walker WE, Booth CJ and Goldstein DR. TLR9 and IRF3 cooperate to induce a systemic inflammatory response in mice injected with liposome:DNA. Molecular Therapy [Nature Publishing Group] 2010, 18:775-84. 
  11. Silver A, Arjona A, Walker WE, Fikrig E. Circadian control of toll-like receptor 9-mediated innate and adaptive immunity. Immunity. 2012, 36:251-61.
  12. Arjona A, Silver AC, Walker WE, Fikrig E. Immunity's fourth dimension: approaching the circadian-immune connection. Trends Immunol. 2012, 33:607-12. (review article)
  13. Walker, WE, Bozzi AT and Goldstein DR. IRF3 contributes to sepsis pathogenesis in the mouse cecal ligation and puncture model. Journal of Leukocyte Biology. 2012, 92:1261-8.
  14. You F, Wang P, Yang L, Yang G, Zhao YO, Qian F, Walker W, Sutton R, Montgomery R, Lin R, Iwasaki A, Fikrig E. ELF4 is critical for induction of type I interferon and the host antiviral response. Nature Immunology. 2013, 14:1237-46.
  15. Mannam P, Shinn A, Srivastava A, Neamu R, Walker W, Bohanon M, Merkel J, Kang MJ, Dela Cruz C, Ahasic A, Pisani M, Trentalange M, West AP, Shadel G, Shen J, Elias J, and Lee P. MKK3 regulates mitochondrial biogenesis and mitophagy in sepsis-induced lung injury. The American Journal of Physiology - Lung Cellular and Molecular Physiology. Accepted
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