Microbiology and Immunology
685 W. Baltimore St, Baltimore, MD 21201
Education and Training
2010 Ph.D. in Microbiology at Chinese Academy of Sciences Institute of Microbiology, Beijing, China.
Pathogens, infections, inflammation, immunity, IMD signaling, and inflammasomes
p47 licenses activation of the immune deficiency pathway in the tick Ixodes scapularis. McClure Carroll EE, Wang X, Shaw DK, O'Neal AJ, Oliva Chávez AS, Brown LJ, Boradia VM, Hammond HL, Pedra JHF. Proc Natl Acad Sci U S A. 2018 Dec 17. doi: 10.1073/pnas.1808905116
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 JH. Nature Communications 2017. 8:14401. doi: 10.1038/ncomms14401.
Deviant behavior: Tick-borne pathogens and inflammasome signaling. Shaw DK, McClure EE, Wang X, Pedra JHF. Vet Sci. 2016 Sep 28;3(4). doi: 10.3390/vetsci3040027
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. The prostaglandin E2-EP3 receptor axis regulates Anaplasma phagocytophilum-mediated NLRC4 inflammasome activation. PLoS Pathog. 2016 Aug 2;12(8):e1005803. doi:10.1371/journal.ppat.1005803. PMID:27482714.
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. (2016) Infect Immun. 2016 May 24;84(6):1796-805. doi: 10.1128/IAI.01526-15.
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 JF, Zhou Y, Shi GP, Sutterwala FS, Kotsyfakis M, Pedra JHF. (2014) Infect Immun. 2014 82(6):2553-64. doi: 10.1128/IAI.01679-14.
Dr. Wang’s research program mainly focuses on the biology of the human granulocytic anaplasmosis agent Anaplasma phagocytophilum and the Lyme disease spirochete Borrelia burgdorferi, especially in the aspect of interactions between bacterial pathogens and the hosts. In general, Dr. Wang’s research focuses on the following three aspects.
- The tick IMD signaling pathway: On the one hand, the E3 ubiquitin ligase X-linked inhibitor of apoptosis (XIAP)-regulatedthe immune deficiency (IMD) pathway plays a pivotal role in controlling microbial transmission at the interface of bacterial pathogens and tick host Ixodes scapularis. Through biochemistry approaches, Dr. Wang revealed that XIAP interfaces with the tick IMD signalling pathway by interacting with the upstream E2 conjugating enzyme Bendless. As an E3 enzyme, XIAP also polyubiquitylates the substrate p47 in a K63-dependent manner through a specific interaction with the p47 ubiquitin-like (UBX) domain. After p47 is ubiquitylated, it interacts with the downstream NF-κB regulatory protein Kenny to impair the cleavage of the NF-κB molecule Relish to further affect the global proteins expression profile in response to the bacterial colonizations.
- Inflammasome biology associated with rickettsial agent infections: On the other hand, inflammasome protein scaffold plays an important role in defending rickettsial agents invasion at the interface of pathogens and the human host. By using Anaplasma phagocytophilum, Dr. Wang identified a phospholipase A2-prostaglandin E2-EP3 receptor signaling axis-regulated activation of the non-canonical NLRC4 inflammasome against the bacterial infection.
- The roles of tick salivary proteins in facilitating bacterial transmission: Tick saliva contains a number of proteins that inhibit host immunity and facilitate pathogens transmission. At the interface of tick-pathogens-human, Dr. Wang discovered that the assmbly of the NLRC4 inflammasome is diminished through the interaction of a tick salivary gland protein sialostatin L2 with the human protein Annexin A2, which can makes pathogens evade from the human immune survillance during the bacterial transmission.
American Society for Microbiology
American Society for Rickettsiology