F A C U L T Y P R O F I L E
LOIKE, JOHN D., Ph.D.
Regulation of leukocyte chemotaxis through physiological and pathological matrices.
Office: Black Building| 11th floor | Room 1111
My current research interest focuses on the role of immune cells and inflammation in a variety of disease states including cancer, Alzheimer’s disease, and Parkinson’s disease. In our model of melanoma, we show that a critical concentration of CD8+ cytolytic killer T- cells is required to eradicate the tumor. In addition, only a small percent of the CD8+ T- cells are actually cytolytic. We are now examining methods to increase the percentage of cytolytic T- cells in order to dramatically improve the eradication of this tumor. In Alzheimer’s disease we have identified the pivotal role of scavenger receptors in microglial cell processing of extracellular beta amyloid. Extracellular beta amyloid fibril accumulation is thought to trigger an inflammatory response that promotes neurodegeneration in Alzheimer’s disease. We are examining methods to reduce neuroinflammation in this disease. In Parkinson’s disease (PD), extracellular accumulation of alpha synuclein and nitrated alpha synuclein are thought to trigger neurodegeneration. We have identified beta 2 integrins and CD36 scavenger receptors in the interaction of microglial cells with matrix-bound synucleins and are examining how these receptors function in clearing extracellular synucleins. In addition, we show data that neurodegeneration in PD is also mediated by a CD8+ T cells that specifically target the dopaminergic neurons destroyed in the substantia nigra in these patients. Our goal here is to develop protocols to attenuate or stop T- cell mediated neurodegeneration in PD. In addition to my research and teaching in immunology, I teach and publish on current dilemmas in bioethics.
Cebrián, C., Budhu, S., Zucca, F.A., Mandelbaum, J.,Vonsattel, J.P., Zecca, L., Loike, J.D., Sulzer, D. MHC-I expression by catecholamine neurons and its potential role in neuroinflammation. Accepted with revisions, J Exp. Med. 2014.
Margolit, Y., Levy, O., Loike, J.D., Advanced Reproductive Technologies: Reevaluating Modern Parentage,
Harvard Journal of Law and Gender, in press 2013.
Loike, J.D., Rush, B.S., Schweber, A., Fischbach, R. L. Lessons Learned from Undergraduate Students in Designing a Science-based Course in Bioethics, Cell Biology Education—A Journal of Life Science Education, December, 2013.
Loike, J. D., and Fischbach, R. L. Ethical Challenges in Biodefense and Bioterrorism, J Bioterr Biodef, 2013, S01-S12.
Loike, J.D., Hirano, M., Margalit, H., Three-Way Parenthood: dealing with the logistics of embryos created by three-parent IVF technologies that avoid the transmission of mitochondrial disease. Oct 1, The Scientist, 2013.
Loike, J.D., Plitt, A., Kothari, K., Zumeris, J., Budhu, S., Kavalus, K., Ray, Y., and Jacob, H.,Surface Acoustic Waves Enhance Neutrophil Killing of Bacteria, PLOS One, 2013 http://dx.plos.org/10.1371/journal.pone.0068334.
Phani, S., Loike, J.D., Przedborski, S. Neurodegeneration and Inflammation in Parkinson’s Disease.
Parkinsonism Related Disorders. Jan;18 Suppl 1:S207-9, 2012.
Miller, J. Loike, J.D. BioCEP: A Model Educational Program for Cross-cultural Bioethics.
Cambridge Quarterly of Healthcare Ethics, 21:409-415, 2012.
Budhu, S., Loike, J.D., Constantinescu, A., Pandolfi, A., Clynes, R., and Silverstein, S.C. CD8+ T-cell concentration determines the efficiency of killing of cognate antigen-expressing syngeneic mammalian cells in vitro and in vivo.
Journal of Experimental Medicine, 207:223-235, 2010.
Zhang, W., Phillips, K., Wielgus, A.R., Liu, J., Albertini, A., Zucca, F.A., Faust, R., Qian, Y., Miller, D.S., Chignell, C.F., Wilson, B., Jackson-Lewis, V., Przedborski,S., Joset, D., Loike, J.D., Hong, J., Sulzer, D., and
Zecca,.L. Microglial Mac-1 is involved in phagocytosis of neuromelanin and neuronal death: implications for Parkinson's disease’’ Neurotoxicity Research Jan;19(1):63-72, 2010.
Talloczy, Z., Santambrogio, L., Joset, D., Ray, Y., Martinez, J., Mizushima, N., Loike, J.D., David Sulzer. Methamphetamine inhibits antigen processing and presentation in dendritic cells and phagocytosis by macrophages. PLOS-Pathogen 4:28-48, 2008.