Microbiology and Immunology
685 West Baltimore Street, Baltimore, MD 21201
Education and Training
1998 B.Sc., Biological Sciences, Universidade Federal de Vicosa, Brazil
2000 M.Sc., Agricultural Chemistry, Universidade Federal de Vicosa, Brazil
2004 Ph.D., Entomology, Purdue University, Mentor: Barry R. Pittendrigh
2004 - 2007 Post-Doctoral Fellowship, Yale University School of Medicine, Mentor: Erol Fikrig, Howard Hughes Medical Institute
2007 - 2009 Associate Research Scientist, Yale University School of Medicine, Mentor: Erol Fikrig, Howard Hughes Medical Institute
I completed my college and Master of Science degrees in Biology and Chemistry in Brazil. Then, I immigrated to the United States and received a doctoral degree in Entomology at Purdue University where I was mentored by Dr. Barry Pittendrigh (currently at Michigan State University). My post-doctoral training was focused on microbial pathogenesis and immunology at Yale University under the supervision of Dr. Erol Fikrig (Chief of Infectious Diseases/HHMI Investigator). In 2009, I joined the University of California at Riverside as an independent investigator. In 2013, I relocated to the University of Maryland, Baltimore School of Medicine.
Tick-borne diseases; rickettsial infections; innate immunity; nod-like receptors; inflammasome; humoral responses in arthropods
Engineering of obligate intracellular bacteria, challenges and paradigms. McClure EE, Chávez ASO, Shaw DK, Carlyon JA, Ganta RR, Noh SM, Wood DO, Bavoil PM, Brayton KA, Martinez JJ, McBride JW, Valdivia RH, Munderloh UG, Pedra JHF. Nature Reviews Microbiology, 2017 Jun 19. doi: 10.1038/nrmicro.2017.59.
Infection-derived lipids elicit an immune deficiency circuit in arthropods. Shaw DK, Wang X, Brown LJ, Chávez AS, Reif KE, Smith AA, Scott AJ, McClure EE, Boradia VM, Hammond HL, Sundberg EJ, Snyder GA, Liu L, DePonte K, Villar M, Ueti MW, de la Fuente J, Ernst RK, Pal U, Fikrig E, Pedra JHF. Nature Communications 2017 8:14401.
The prostaglandin E2-EP3 receptor axis regulates Anaplasma phagocytophilum-mediated NLRC4 inflammasome activation. Wang X, Shaw DK, Hammond HL, Sutterwala FS, Rayamajhi M, Shirey KA, Perkins DJ, Bonventre JV, Velayutham TS, Evans SM, Rodino KG, VieBrock L, Scanlon KM, Carbonetti NH, Carlyon JA, Miao EA, McBride JW, Kotsyfakis M, Pedra JHF. PLoS Pathogens 2016 12(8):e1005803
The tick protein sialostatin L2 binds to Annexin A2 and inhibits NLRC4-mediated inflammasome activation. Wang X, Shaw DK, Sakhon OS, Snyder GA, Sundberg EJ, Santambrogio L, Sutterwala FS, Dumler JS, Shirey KA, Perkins DJ, Richard K, Chagas AC, Calvo E, Kopecký J, Kotsyfakis M, Pedra JHF. Infection and Immunity 2016 84(6):1796-805.
Genomic insights into the parasitic vector of Lyme disease, Ixodes scapularis. Ixodes scapularis International Consortium. Nature Communications, 2016 7:10507
The tick salivary protein sialostatin L2 inhibits caspase-1-mediated inflammation during Anaplasma phagocytophilum infection. Chen, G, Wang, X, Severo, MS, Sakhon, OS, Sohail, M, Brown, LJ, Sircar, M, Snyder, GA, Sundberg, EJ, Ulland, TK, Olivier, AK, Andersen, J, Zhou, Y, Shi, G-P, Sutterwala, FS, Kotsyfakis, M, Pedra, JHF. Infection and Immunity 2014 82:2553-2564.
Tick Anti-Inflammatory Proteins
Arthropod saliva possesses anti-hemostatic, anesthetic, and anti-inflammatory properties that facilitate feeding and, inadvertently, dissemination of pathogens. Recently, several vector-borne pathogens have been shown to induce nod-like receptor (NLR) activation in immune cells. NLRs are innate immune pattern recognition molecules involved in detecting microbial molecules and danger signals. Nod1/2 signaling results in activation of the nuclear factor (NF)-κB and the mitogen-activated protein (MAP) kinase pathways. Caspase-1 NLRs regulate the inflammasome - a protein scaffold that governs the maturation of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18. We focus on the discovery of tick proteins that counters nod-like receptor (NLR) sensing upon pathogen infection. We also elaborate on the possible anti-inflammatory properties of tick proteins as therapeutic drugs against chronic sterile diseases.
The Tick Immune System
The increase in knowledge observed for arthropod-pathogen interactions in the past decade can be directly correlated to the availability of multiple sequenced insect genomes. Comparative genomics analysis coupled to functional assays uncovered evolutionarily conserved signaling pathways and provided important insights towards the understanding of insect immunity. However, extrapolating this approach to non-insect arthropods, such as the tick Ixodes scapularis, sometimes constitutes a problem because of the lack of distinguishable protein homologues and incorrect annotation of genes due to low sequence coverage or incompleteness of a particular genome. We are studying the non-canonical immune deficiency (IMD) signaling pathway of the Lyme disease tick I. scapularis. We are characterizing this signaling relay based on biochemical, molecular and structural biology information. This novel immune pathway in ticks has broad implications for the arthropod biology community.
Lipids exhibit an immense combinatorial and structural diversity due to the complexity of head groups, acyl chains, and backbone structures. They are also critically important for an immune response against a microbial pathogen. Through a mass spectrometric lipidomics approach, we discovered bacterial bioactive molecules that affect cytokine secretion upon infection. We are currently performing refined chemistry coupled to direct spatial visualization to identify bacterial lipids that affect inflammation. We are also focused on the host eicosanoid signaling. We observed that macrophages secrete prostaglandins upon bacterial stimulation, and inhibition of cyclooxygenases hampers the production of pro-inflammatory cytokines. Therefore, we are characterizing the prostaglandin signaling pathway and identifying host lipid immunomodulators upon bacterial infection. This research should identify lipid biomarkers that may distinguish pathogenic bacteria and unravel the role of lipid mediators in acute inflammation.
2006-2007 Brown-Coxe Post-Doctoral Fellowship, Yale University
2007-2011 Mentored Public Health Research Scientist Development Award (K01), Centers for Disease Control and Prevention
2006-present General Member, American Society for Rickettsiology
2011-present General Member, American Society for Microbiology
2011-present General Member, American Association of Immunologists