21-242 Lineberger Comprehensive Cancer Center
Campus Box 7295
Chapel Hill, NC 27599
Inflammation constitutes an important host defense mechanism. However, dysregulation of inflammation as occurs in the case of inheritable autoinflammatory diseases or uncontrolled inflammation as in septic shock is in some cases untreatable and at worst case is damaging to the host. Understanding the roles of signaling components that initiate, regulate and/or propagate inflammation is vital to the development of therapeutic targets.
I am interested in using molecular approaches to investigate specific roles of inflammatory mediators and regulators. I have developed molecular tools to study broad mRNA expression profiling of human or mouse cells and tissues. Each species-specific custom-designed microarray encompasses more than 1500 inflammation-related gene targets. Also, I have applied the use of protein arrays that support the coordinated broad examination of protein abundance for up to 200 proteins. Lastly, I have utilized bioinformatics software to investigate the biological relevance represented by the RNA and/or protein expression profiles to discern pathways and networks of interacting factors that are involved in inflammation.
In addition, I am interested in understanding the cross-talk between and regulation of innate and adaptive immune responses in hosts exposed to damaging insults or foreign tissue. Currently, I am collaborating with Dr. Jenny Ting and researchers in her lab to study immune responses to transplanted organs and inflammation-induced damage due to pathogen infection or radiation treatment. We use gene knock out mice to examine the contribution of specific regulators, such as mice deficient in the expression of C2ta, I-Ab, Cd4, Cd8, Cias1, Monarch1 or Myd88. Consequently, production or lack of inflammatory cytokines and cell profiles in affected tissues of these deficient strains will inform us about the roles of these adaptive and innate immune regulators in compromised hosts.
Davis BK, Roberts RA, Huang MT, Willingham SB, Conti BJ, Brickey WJ, Barker BR, Kwan M, Taxman DJ, Accavitti-Loper MA, Duncan JA, Ting JP (2011): Cutting edge: NLRC5-dependent activation of the inflammasome. J Immunol. 186(3):1333-7.
van Deventer HW, Burgents JE, Wu QP, Woodford RM, Brickey WJ, Allen IC, McElvania-Tekippe E, Serody JS, Ting JP (2010): The inflammasome component NLRP3 impairs antitumor vaccine by enhancing the accumulation of tumor-associated myeloid-derived suppressor cells. Cancer Res. 70(24):10161-9.
Jha S, Srivastava SY, Brickey WJ, Iocca H, Toews A, Morrison JP, Chen VS, Gris D, Matsushima GK, Ting JP (2010): The inflammasome sensor, NLRP3, regulates CNS inflammation and demyelination via caspase-1 and interleukin-18. J Neurosci. 30(47):15811-20.
Hernandez ML, Lay JC, Harris B, Esther CR Jr, Brickey WJ, Bromberg PA, Diaz-Sanchez D, Devlin RB, Kleeberger SR, Alexis NE, Peden DB (2010): Atopic asthmatic subjects but not atopic subjects without asthma have enhanced inflammatory response to ozone.
J Allergy Clin Immunol. 126(3):537-44.e1.
Bergstralh DT, Conti BJ, Moore CB, Brickey WJ, Taxman DJ, Ting JP (2007): Global functional analysis of nucleophosmin in Taxol response, cancer, chromatin regulation, and ribosomal DNA transcription. Exp Cell Res. 313(1):65-76.
van Deventer HW, O'Connor W Jr, Brickey WJ, Aris RM, Ting JP, Serody JS (2005): C-C chemokine receptor 5 on stromal cells promotes pulmonary metastasis. Cancer Res. 65(8):3374-9.