Immunopathology Cancer, Immunosenescence in Aging: Paving the Way for New Drug Therapies Fernando Macian-Juan, MD, PhD Professor, Department of Pathology 718.430.2630 fernando.macian@einsteinmed.org View Profile The laboratory of Fernando Macian, MD, PhD, focuses on four areas of research. These include: regulation of T cell tolerance; reversal of tumor-induced T cell tolerance as an immunotherapeutic approach; autophagy and T cell function; and aging in the T cell compartment. One mechanism of peripheral lymphocyte tolerance is anergy, an intracellular process in which antigen receptors become un-coupled from their downstream signaling pathways. Anergic lymphocytes remain in a state of non-responsiveness that prevents harmful responses to self-tissues. Dr. Macian and his team have shown that tolerant T cells express a novel set of anergy-associated genes. Their analysis of the specific genes activated in anergic T cells supports the existence of distinct mechanisms of tolerance induction, including interference with signaling pathways coupled to antigen receptors and transcriptional modulation. The Macian lab is studying the role of these processes in peripheral T cell tolerance, and how they may be involved in regulatory T cell-mediated suppression and T cell exhaustion. Cell homeostasis requires a regulated balance between synthesis and degradation of cellular components. Autophagy, a catabolic pathway for degradation in lysosomes and recycling of intracellular components, is a major system involved in cellular quality control. Dysregulation of autophagy has been proposed as a cause of altered function of different organs and tissues in the elderly and of the development of age-related pathologies. The Macian lab is characterizing the role of different forms of autophagy in T cells and analyzing the consequences of altered autophagic activity with age as a mechanism to explain the diminished T cell function that characterizes immunosenescence.