The main interest of our lab is understanding how cytokine expression and function is regulation during infection and inflammatory responses in human immune system cells. Our current focus is to identify how cytokines function in disease states and to test for beneficial or detrimental immune responses to potential novel cytokine-related therapeutics. In particular our projects examine the roles played by the IL-12 family of cytokines.
We have demonstrated that IL-27, a key immunoregulatory cytokine belonging to the IL-12 cytokine family activates myeloid cells to secrete proinflammatory cytokines. Furthermore, we have also shown that IL-27 functions to augment responses triggered by innate immune cell receptors such as Toll-like receptor 4 (TLR4). Since IL-27 functions to link the innate and adaptive immune responses, it is a key player in the regulation of how our immune systems defends the body against pathogen invasion.
Ongoing research projects include:
1) Defining how IL-27 affects TLR4-driven anti-bacterial immunity
2) Examining the molecular mechanisms behind anti-viral immune responses led by IL-27
3) Identifying how IL-27 impacts immune responses in prostate cancer
Petes C., V. Mintsopoulos, RL Finnen, BW Banfield and K.Gee. 2018. The effects of CD14 and IL-27 on induction of endotoxin tolerance in human monocytes and macrophages. Submitted to Journal of Biological Chemistry. Nov 9;293(45):17631-17645.
Petes C., N. Odoardi, S. M. Plater, N. L. Martin, K. Gee. 2018. IL-27 amplifies cytokine responses to Gram-negative bacterial products and Salmonella typhimurium infection. Accepted.
Petes, C., M.K. Mariani, Y.Yang, N. Grandvaux, and K.Gee. 2018. IL-6 inhibits IL-27- and IL-30-mediated inflammatory responses in human monocytes. Frontiers in Immunology. Feb 15;9:256.
Banete A., K. Seaver, D. Bakshi, K. Gee, and S. Basta 2018. On taking the STING out of immune activation. Invited Review for Journal of Leukocyte Biology. Feb 12. doi: 10.1002/JLB.2MIR0917-383R.
C. Petes, N. Odoardi, and K. Gee. 2017. The toll for trafficking: Toll-like receptor 7 delivery to the endosome. Frontiers in Immunology. Sep 4;8:1075.
C. Petes, C.Wynick, C.Guzzo, D.Mehta, S.Logan, S.Basta, A.Cooper, and K. Gee. 2017. IL-27 enhances LPS-induced IL-1beta in human monocytes and murine macrophages. Journal of Leukocyte Biology: Jul;102(1):83-94.
J. Richard, J.Prévost, B.Von Bredow, S. Ding, M. Coutu, N. Brassard, B. Melillo, F. Bibollet-Ruche, B.H. Hahn, D.E. Kaufmann, A.B. Smith III, J.Sodroski, K. Gee, S. J. Neil, D. T. Evans and A.Finzi. 2017. BST-2 Expression Modulates Small CD4 Mimetics sensitization of HIV-1-infected cells to ADCC. Journal of Virology. May 12;91(11). pii: e00219-17.
Wynick C., C. Petes, and K.Gee 2014. Interleukin-27 mediates inflammation during chronic disease. The Journal of Interferon and Cytokine Research. (10):741-9.
Guzzo, C., M. Jung, A. Graveline, B.W. Banfield, and K. Gee. 2012. IL-27 regulates BST-2 expression independently of type-I IFN on human monocytes and T cells. Scientific Reports 2:974.
Guzzo, C., W.M. Hopman, N.F.Che Mat, W. Wobeser, and K. Gee. 2012. IL-27-induced gene expression is downregulated in HIV-infected subjects. PlosOne. 7(9):e45706.
Guzzo, C., A. Ayer, B Banfield, S. Basta, and K. Gee. 2012. Interleukin-27 induces TLR4 expression on human monocytes via a STAT3 and NF-kB dependent pathway. Journal of Immunology. Jan 15;188(2):864-73.
Che Mat, NF, X. Zhang, C. Guzzo, and K. Gee. 2011. IL-23-induced IL-23 receptor subunit expression is mediated by the JAK/STAT pathway in human CD4 T cells. Journal of Interferon and Cytokine Research. 2011 (4):363-71.
Guzzo, C., N.F.Che Mat, and K. Gee. 2010. Interleukin-27 induces a STAT1- and STAT3-dependent proinflammatory cytokine and chemokine profile in human monocytes. Journal of Biological Chemistry. Aug 6;285(32):24404-11.
Guzzo, C., W.M. Hopman, N.F.Che Mat, W. Wobeser, and K. Gee. 2010. Impact of HIV infection, highly active anti-retroviral therapy, and hepatitis C co-infection on serum interleukin-27 expression. AIDS. Jun 1;24(9):1371-4.
Gee, Katrina Lab
Olena Kourko, PhD student
Natalya Odoardi, MSc student
Co-supervisor with Sam Basta:
Torki Al-Othaimeen, PhD student
Evan Trus, MSc student