Research Interests

  • Multiple Sclerosis: A major focus of the laboratory relates to the study of the immunology of multiple sclerosis and the EAE animal model of MS.
    1. MS Immunoregulation (Tregs/Th17) and innate immunity. We are investigating basic immune function in MS that involves the characterization of TH17 cells, regulatory T cells, monocytes, B cells, and dendritic cells. These studies involve a functional studies and detailed profiling of these subsets in patients with MS.
    2. MS biomarkers. We have had a long-term program to develop blood biomarkers for MS and to link them to disease stage and response to therapy. A major resource for our biomarker program is the CLIMB observational study in patients with MS. The CLIMB study begun in 2000 and we currently follow over 2000 patients with yearly exams, MRI imaging and blood collection. We are also now beginning to collect urine and stool samples. The CLIMB biorepository and cohort serves as an outstanding source to study and develop MS biomarkers. We are currently focusing on antigen arrays, microRNAs (serum and cells), and immune cell profiling. In addition, we are actively studying the gut microbiota in MS.
    3. Experimental Allergic Encephalomyelitis (EAE): EAE serves as the animal model for MS. We investigate both the classic relapsing model and the role of Th17/Th1 and Treg cells and a newly developed chronic model that is driven by the innate immune system. There are many drugs for the treatment of inflammatory stages of MS but no treatment and a poor understanding of progressive MS. Our studies in the progressive EAE model involve the role of microglial cells, astrocytes, lipids and the modulation of the progressive model by nasal induction of regulatory T cells. We hope that understanding basic mechanisms in the NOD model will provide a basis for developing new targets of therapy.
  • Mucosal tolerance. Our laboratory has a long-term interest in the induction of regulatory T cells and the modulation of autoimmune and inflammatory diseases by the mucosal (oral/nasal) route. The laboratory is currently focused on addressing a series of questions related to mucosal tolerance. These include mechanisms by which mucosally administrated anti-CD3 and other antibodies induce regulatory T cells, the role of the microbiota in mucosal tolerance, characterization of LAP+ Th3 type regulatory T cells, adjuvants and other molecules that can enhance mucosal tolerance, the role of AHR signals in the gut, and microRNA and gene signatures in the gut in association with oral tolerance.
  • Microglia. Microglia are key immune cells in the nervous system which play a crucial role in the maintenance of normal CNS homeostasis and in disease processes. We have identified unique microglial signatures in both mice and humans and have developed microglial specific monoclonal antibodies for the study of microglia. We are involved in an extensive investigation of the function of microglia in normal CNS function and during diseases of the nervous system such as EAE, ALS, and Alzheimer’s disease.
  • Alzheimer’s Disease (AD). We are investigating the role of the immune system in AD in both animal models and human subjects. This includes the study of T cell reactivity to amyloid peptides and treatment of animal models by nasal administration of amyloid peptides and proteosome based adjuvants which clear beta amyloid from the CNS. Our laboratory recently received a Transformational Award from the NIH Director’s office to investigate the innate immune system in Alzheimer’s disease. This involves the study of microglial cells and peripheral monocytes in animal models and in AD patients as correlated to PIB imaging and pathology.
  • Amyotrophic Lateral Sclerosis (ALS). We are investigating the role of the innate immune system in ALS in both animal models and patients with ALS. We have observed that the infiltration of monocytes from the periphery contribute to disease in the spinal cord and modulation of these cells ameliorates disease. In addition, we have observed a unique microRNA signature in the blood monocytes from ALS patients that is analogous to what is seen in the animal model. We have identified a prominent role for mir-155 in ALS and are currently investigating the possibility of developing a mir-155 antagomir for the treatment of patients with ALS.
  • Brain tumors. We have initiated a program to understand microRNA patterns in glioblastoma. We are investigating both mouse models and human glioblastoma. In addition, we are investigating the effect of modulation of glioblastoma by targeting regulatory T cells.
  • Animal Models: We have established several animal models in the laboratory for the study of immune based diseases. These animal models include acute and chronic EAE, type 1 and type 2 diabetes, arthritis, lupus, stroke, ALS and Alzheimer’s disease.