Gema Mendez-Lagares, PhD

Gema Mendez-Lagares, PhD

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I have fifteen years of experience in T-cell biology and HIV pathogenesis. First, I studied immune dysregulation in HIV-infection, focusing my research on the contribution of regulatory T cells (T-regs) to the heightened activation state of patients with low CD4 T-cell restoration under suppressive HAART. During my postdoctoral training I progressed to study the immunologic changes associated with CMV infection and their impact on the immune function of the host and the efficacy of RhCMV-based SIV vaccines. I questioned if expansion of NK-CTLs– NK-CTLs are characterized by surface expression of HLA class I specific inhibitory receptors most often associated with NK cells (e.g., NKG2A)– contributed to the efficacy of RhCMV-based vaccines against SIV. This work led to a publication in the Journal of Clinical Investigation (JCI 21:148542), where we show an expansion of innate-like CD8+ T cells following RhCMV infection or vaccination which is driven largely by host IL-15 expression.

Now I am particularly interested in how mTOR inhibitors can improve anti-HIV T-cell function. HIV-1 infection generally increases mTORC1 activity in order to promote successful viral integration and replication, as well as T-cell exhaustion. Our preliminary data show that although therapeutic T cell vaccination can effectively generate CD8+ T cell responses, in most case this antiviral activity is very short lived and insufficient by the time of treatment interruption to delay rebound or the systemic spread of SIV. My interest centers on the immunometabolic conditions that will permit host control of viral replication after ART withdrawal. I am focused on implementing a complementary approach to target host factors to simultaneously restrict virus replication and preserve T cells with the capacity for future replication.

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