1. Molecular mechanism of Sphingosine-1-phosphate signaling in MS

Sphingosine-1-phosphate (S1P) signaling is a key signaling pathway in the pathogenesis of MS. Blocking S1P receptor with FTY-720 (first orally available MS therapy) blocks immune cell egress. However, how this affects the critical pathways involved in MS / EAE pathogenesis (Th1, Th17, Th2) is unknown. Utilizing human MS brain tissue samples and EAE model, we will decipher the molecular pathways that are affected by pertubating the S1P system.

2. Biomarkers to predict disease activity in Neuromyeltis optica

Neuromyeltisoptica (NMO) is an autoimmune inflammatory demyelinating disorder of the central nervous system (CNS), primarily involving the spinal cord and optic nerves. Our previous work utilizing multi-parameter flow cytometry demonstrated different cellular profiles in NMO-IgG(+) and NMO-IgG(-) cases. In this follow up prospective study, we will utilize flow cytometry and Luminex multiplex cytokine analysis to correlate the alterations in cellular and molecular profiles during different stages of disease. Findings from this study will shed light on the underlying disease pathogenesis and guide with clinical management.

3. Neurotrophin TrkB signaling in MS

Most patients with RRMS will result in progressive MS within 20-25 years, However, little is known about how to protect and repair the nervous system. Our laboratory is studying the effects of neurotrophin TrkB signaling in MS. TrkB signaling is known to be neuroprotective. We have demonstrated that TrkB activation also down-regulated inflammation. This project focuses on the molecular and cellular mechanisms of immune modulation and neuroprotection by TrkB utilizing TrkB agonist small molecular LM22A-4.

4. Monitoring response to therapy in MS

We would like to develop diagnositc tools that are more sensitive than what MRI imaging could currently provide in management of MS cases. This project will correlate blood and imaging biomarkers to predict response to therapy in MS. This work is performed in collaboration with Dr. Brian Rutt from the Lucas Imaging Center.