Jacki Kornbluth, Ph.D.
Tumor immunology, molecular and functional studies of natural killer and other cytotoxic effector cells.
My laboratory is studying the role of the immune response to tumor cells, with particular emphasis on the role of natural killer (NK) cells. NK cells are a small population of circulating white blood cells with the ability to kill tumor cells upon contact. Treatment of NK cells with agents such as interleukin-2 (IL-2) and interferon (IFN) enhances their killing activity and expands the repertoire of tumor cells capable of being recognized and killed. IL-2 and IFN enhancement of NK activity requires new RNA and protein synthesis. This has led us to the cloning and characterization of new genes induced by IL-2 and IFN in NK cells that are associated with tumor killing activity.
We have identified several novel genes expressed selectively in activated NK cells. One of these genes, designated NKLAM, is currently under extensive investigation in our laboratory. It has been shown to be essential for the anti-tumor activity of NK cells. Studies are now directed at characterizing the role of the NKLAM protein in the killing process mediated by NK cells as well as cytotoxic T cells and macrophages. Some of the other novel genes that have been cloned are also under study.
My laboratory is also developing strategies to accentuate anti-tumor immunity in cancer patients. We have found that oral administration of glutamine to animals or patients enhances NK function and inhibits and/or prevents breast tumor growth. In patients with myeloma, NK function is normal; however, the tumor cells are inherently resistant to NK lysis. We have identified several agents that can increase the susceptibility of myeloma tumor cells to NK-mediated killing and are in the process of studying their specific mode of action.
Feng Z, Cao Y, Kornbluth J, Gray P, Fahr M, and Klimberg VS: Glutamine prevents DMBA-induced breast cancer growth. Surgical Forum 47:524-526, 1996.
Munshi NC, Govindarajan R, Drake R, Ding LM, Iyer R, Saylors R, Kornbluth J, Marcus S, Chiang Y, Ennist D, Kwak L, Reynolds C, Tricot G, and Barlogie B: Thymidine kinase (TK) gene transduced human lymphocytes can be highly purified, remain fully functional and are killed efficiently with ganciclovir. Blood 89:1334-1340, 1997. PMID: 9028956.
Kozlowski M, Schorey J, Portis T, Grigoriev V and Kornbluth J: NKLAM: A novel gene selectively expressed in cells with cytolytic function. J. Immunol.163:1775-1785, 1999.
Portis T, Anderson J, Esposito A and Kornbluth J: Gene structure of human and murine NKLAM, a gene associated with cellular cytotoxicity. Immunogenetics 51:546-555, 2000.
Shallal S and Kornbluth J: CD9 expression enhances the susceptibility of myeloma cell lines to cell-mediated cytolysis. Blood 96:224-233, 2000.
Kaufmann Y, Kornbluth J, Feng Z, Fahr M, Schaefer RF and Klimberg VS: Effect of glutamine on the initiation and promotion phases of DMBA-induced mammary tumor development. J. Parent. Ent. Nut. 27:411-418, 2003.
Fortier J and Kornbluth J. NK Lytic-Associated Molecule, involved in NK cytotoxic function, is an E3 ligase. J. Immunol. 176:6454-6463, 2006.
Ambrose EC and Kornbluth J. Downregulation of uridine-cytidine kinase like-1 decreases proliferation and enhances tumor susceptibility to lysis by apoptotic agents and natural killer cells. Apoptosis 14: 1227-1236, 2009.
Hoover RG, Gullickson G and Kornbluth J: Impaired NK cytolytic activity and enhanced tumor growth in NK Lytic-Associated Molecule (NKLAM)-deficient mice. J. Immunol. 183: 6913-69211, 2009.
McHowat J, Gullickson G, Hoover RG, Sharma S, Turk J and Kornbluth J: Platelet-activating factor and metastasis: Calcium-independent phospholipase A2β deficiency protects against breast cancer metastasis to the lung. Am. J. Physiol. Cell Physiol. ajpcell.00502.2010; published ahead of print January 12, 2011. doi:10.1152/ajpcell.00502.2010.
Honors and Awards
1981-1983 National Institutes of Health Postdoctoral Research Services Award
1980 Doctor of Philosophy with Honors, Cornell University
1976-1978 National Institutes of Health Pre-doctoral Fellowship
1976 Bachelor of Science with Honors and Distinction, Cornell University
Professional Organizations and Associations
American Association of Immunologists
American Association for Cancer Research
American Society for Microbiology
The Society for Natural Immunity