- BIOL 221 Foundations of Biology I
- BIOL 250 Microbiology
- BIOL 402 Current Topics in Virology & Immunology
- BIOL 491 Cancer Immunobiology
Research and Creative Activities
- Molecular & Cellular Immunology
- Cancer Biology
Glycoprotein 96 (gp96) is a mammalian ER chaperone which is required for the proper folding and expression of Toll-like receptors (TLRs) and integrins. TLRs are responsible for sensing an infection and initiating immunity, while integrins are important for cell-cell adhesion necessary in an immune response. Hence, gp96 is an important immune chaperone. In order to fold TLRs, gp96 further requires the help of a co-chaperone, canopy 3 (CNPY3). Dr. Del Valle previously identified the putative fruit fly (Drosophila) orthologs of gp96 and CNPY3, termed glycoprotein 93 (gp93) and CNPYb, respectively.
Both TLRs and macrophages (an immune cell) have been implicated in colon cancer, yet the specific details are not clear. Putting the two together, Dr. Del Valle identified the importance of TLRs specifically on macrophages for driving both colitis and inflammation-induced colon tumorigenesis. Specifically, TLR signaling on macrophages was associated with a larger tumor burden, increased mutation of the beta-catenin gene coupled with decreased DNA repair, and increased expression of pro-inflammatory cytokines (signaling molecules).
Cancer immunotherapy involves methods of inciting an immune response to fight cancer. Dr. Del Valle investigated one such technique utilizing antibodies to stimulate the surface costimulatory molecules 4-1BB and OX40 on helper T cells. Signaling through costimulatory receptors is a necessary step in T cell activation. Another necessary step, Dendritic cells also stimulate the T cells by presenting a tumor-associated molecule required for targeting the tumor cells. With the addition of specific cytokines, these helper T cells secrete interferon gamma, an important cytokine which next stimulates cytotoxic T cells within the tumor microenvironment. Now activated, the cytotoxic T cells are capable of directly killing the tumor cells, as demonstrated in a melanoma model.
- Ph.D. Biomedical Sciences, Immunology concentration 2013 University of Connecticut, Farmington, CT.
- B.A. Biology, Religion minor 2005 Boston University, Boston, MA.
- Del Valle CM, Maxwell JR, Xu MM, Menoret A, Mittal P, Tsurutani N, Adler AJ, Vella AT. “Costimulation induces CD4 T cell antitumor immunity via an innate-like mechanism,” Cell Reports, 2019; 27 (5): 1434-45. PMCID: PMC6508096
- Morales C, Li Z. “Drosophila canopy b is a cochaperone of glycoprotein 93,” The Journal of Biological Chemistry, 2017; 292(16): 6657-6666. PMCID: PMC5399114
- Morales C, Rachidi S, Hong F, Sun S, Ouyang X, Wallace C, Zhang Y, Garret-Mayer E, Wu J, Liu B, Li Z. “Immune chaperone gp96 drives the contributions of macrophages to inflammatory colon tumorigenesis,” Cancer Research, 2014; 74(2): 1-14. PMCID: PMC4002507
- Liu B, Staron M, Hong F, Wu X, Sun S, Morales C, Crosson C, Tomlinson S, Kim I, Wu D, Li Z. “Essential roles of grp94 in gut homeostasis via chaperoning canonical Wnt pathway,” PNAS, 2013; 110(17): 6877-82. PMCID: PMC3637754
- Sugrue ML, Vella KR, Morales C, Lopez ME, Hollenberg AN. “The thyrotropin-releasing hormone gene is regulated by thyroid hormone at the level of transcription in vivo,” Endocrinology, 2010; 151(2): 793-801. PMCID: PMC2817611
- Morales C, Wu S, Yang Y, Hao B, Li Z. “Drosophila glycoprotein 93 is an ortholog of mammalian heat shock protein gp96 (grp94, HSP90b1, HSPC4) and retains disulfide bond-independent chaperone function for TLRs and integrins,” Journal of Immunology, 2009; 183(8): 5121-28. PMCID: PMC2856694
- Astapova I, Lee LJ, Morales C, Tauber S, Bilban M, Hollenberg AN. “The nuclear corepressor, NCoR, regulates thyroid hormone action in vivo,” Proceedings of the National Academy of Sciences of the USA, 2008; 105(49): 19544-49. PMCID: PMC2614797
American Association of Immunologists - member