My research focus is mainly in the areas of neuroinflammation and immunology working together with Dr. Etty (Tika) Benveniste, Senior Vice Dean for Basic Sciences/Professor. My research projects are on understanding cytokine-induced signaling pathways and expression gene profiles in immune cells and brain glial cells, and in central nervous system (CNS) autoimmunity. I also investigate the function of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) and protein kinase CK2 pathways in the pathogenesis of animal models for Multiple Sclerosis (MS), Experimental Autoimmune Encephalomyelitis (EAE), Parkinson’s Disease (PD), Alzheimer’s disease (AD) and colitis.
Specifically, I study the function of SOCS3, a negative regulator of the JAK/STAT pathway, in cells of the myeloid lineage in the pathogenesis of animal models for MS, EAE, PD, AD, colitis and tumorigenesis. My goal is to study the influence of the SOCS3 protein in activation of macrophages, microglia, neutrophils, and dendritic cells (DCs), and in the differentiation of Th1, Th17 and Treg cells, neuronal damage, myelin loss, and effects in the tumor microenvironment. As a PI or co-Investigator, I am involving in several previous and current university, National Multiple Sclerosis Society (NMSS) and NIH-funded grants. I have characterized the signaling pathways that lead to SOCS3 gene induction, and how the absence or presence of the SOCS3 protein influences the functionality of macrophages, microglia, T cells and astrocytes. My studies suggest that SOCS3 is a critical negative regulator for neuroinflammation in animal models of MS, PD and AD and tumor development.
Another major research project is studying the influence of CK2 kinase in the disease development of MS patients, EAE models and colitis models. My focus is on the function of CK2 kinase in differentiation of CD4+ T cells, activation of DCs and activation and differentiation of B cells. My project titled “Function of Protein Kinase CK2 in CD4+ T Cells and Autoimmune Disease” was awarded by The National Multiple Sclerosis Society (NMSS, RG-1606-24794, 2017 - 2020) with Dr. Tika Benveniste and Dr. Laurie Harrington. The project titled “Uncovering the Role of Protein Kinase CK2 in B-cells in the Development of Neuroinflammation” will be submitted in October 05, 2020 to the NIH with collaborators Dr. Tika Benveniste, Dr. Laurie Harrington and Dr. Frances Lund.
Regulation of the JAK/STAT pathway also serves as an approach to new therapeutics for neurodegenerative diseases. As a Co-Investigator, I have a close collaboration with Dr. David Standaert, Department of Neurology, and Dr. Tika Benveniste, on a P50 project (NS108675, $9.5 million) titled “Innate and Adaptive Immunity in Parkinson Disease”, which was recently funded by NINDS Morris K. Udall Centers. I play major roles on Project 1: Role of Innate Immune Cells in Human Parkinson Disease (PI: Standaert, David) and Project 2: Validating the JAK/STAT Pathway as a Novel Therapeutic Strategy in PD (PI: Benveniste, Etty). I contributed to the experimental designs, coordinated the collection and analysis of human subjects with the Clinical Core (PI: Talene Yacoubian), and performed experiments in animal models of PD with coordination of the Animal Core (PI: Laura Volpicelli-Daley). The collaborative project titled “JAK/STAT-mediated astrocyte reaction in AD” with Dr. Qin Wang will be submitted as R01 in February , 2020.
I also collaborate with Dr. Yingzi Cong at the University of Texas Medical Branch at Galveston on studies in the regulation of the pathogenic function of CD4+ T cells in autoimmune diseases. My collaboration with Dr. Amit Gaggar (Department of Medicine, UAB) generated two recent (2016 and 2017) publications on lung injury models. The collaboration with Dr. Xiaoguang (Margaret) Liu in Department of Biomedical Engineering on tumor immunotherapy is ongoing, which resulted in a publication and an awarded grant titled “A targeted mitochondrial luminoptogenetic gene therapy to treat triple negative breast cancer”.
