Background and Research Interests
Isaac received his Bachelors degree in Biochemistry from Harvard College in 2002. He worked in Dr. Jack Strominger’s laboratory on class I MHC cell biology and formation of natural killer-target cell immune synapses. He went on to a Ph.D. in Immunology at Harvard Medical School. In Dr. Michael Carroll’s laboratory, he worked on the role of immunity in Amyotrophic Lateral Sclerosis (ALS), a fatal motor neuron degenerative disease. Focusing on both the central and peripheral nervous systems, he used facs analysis to show T and NK cell infiltration of the nervous system during disease progression. Microglia adopted dendritic cell characteristics. Micro-array profiling of acutely isolated microglia and T cell knockout mice demonstrated a surprising beneficial inflammation in the CNS. In conjunction with Dr. Tom Maniatis’s lab, Isaac discovered the influx of monocytes/macrophages in peripheral nerves of ALS mice. Antibodies and complement deposited in degenerating intra-axonal regions of the PNS. The role of these innate immune cells and humoral molecules in ALS is under investigation.
His current research focuses on 1) Molecular mechanisms of macrophage activation in the peripheral nervous system and 2) the effect of direct neuro-immune interactions on pain neuron sensation.
Kim SS, Ye C, Kumar P, Chiu I, Subramanya S, Wu H, Shankar P, Manjunath N. Targeted delivery of siRNA to macrophages for anti-inflammatory treatment. Mol. Therapy (2010).
Chiu IM, Phatnani H, Kuligowski M, Tapia JC, Carrasco MA, Zhang M, Maniatis T, Carroll MC. Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice. Proc. Natl. Acad. Sci. USA. 106: 20960-5 (2009).
Chiu IM, Chen A, Zheng Y, Kosaras B, Tsiftsoglou SA, Vartanian TK, Brown RH Jr, Carroll MC. T lymphocytes potentiate endogenous neuro-protective inflammation in a mouse model of ALS. Proc. Natl. Acad. Sci. USA. 106: 17913-17918 (2008).
Ma Y, Li J, Chiu I, Wang Y, Sloane JA, Lu J, Kosaras B, Sidman RL, Volpe JJ, Vartanian TK. Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis. J. Cell Biol. 175: 209-15 (2006).
Zhang M, Alicot EM, Chiu I, Li J, Verna N, Vorup-Jensen T, Kessler B, Shimaoka M, Chan R, Friend D, Mahmood U, Weissleder R, Moore FD, Carroll MC. Identification of the target self-antigens in reperfusion injury. J. Exp. Med. 203: 141-52 (2006).
Davis DM, Chiu I, Fassett M, Cohen GB, Mandelboim O, Strominger JL. The human natural killer cell immune synapse. Proc. Natl. Acad. Sci. USA. 96: 15062-7 (1999).
Chiu I, Davis DM, Strominger JL. Trafficking of spontaneously endocytosed MHC proteins. Proc. Natl. Acad. Sci. USA. 96: 13944-9 (1999).