Research Projects

Anti-CD3 targeted immune suppression

Prior studies in our laboratory showed that the monoclonal antibody Teplizumab (anti-CD3) can restore immune tolerance by induction and activation of T regulatory cells that counteract autoreactive T cells. Clinical studies indicate that even a single course of treatment with anti-CD3 can help preserve insulin production in new-onset Type 1 diabetes, and larger trials are currently ongoing to test the drug’s efficacy in both prevention and treatment of new-onset diabetes. (Read more: http://medicine.yale.edu/news/article.aspx?id=1037)

Demethylation and beta cell death

Our laboratory has developed a novel method for detecting beta cell death using a serum marker. The insulin gene DNA is selectively demethylated in beta cells and is released from the cell upon its death. This demethylated DNA is detectable in peripheral blood by a nested PCR technique. We have validated the assay in murine models of diabetes and are expanding its use to patients with new-onset Type 1 Diabetes. This exciting technology may become a new way of detecting beta cell loss before the disease manifests clinically, which would allow earlier interventions in people at risk for developing diabetes. (Read more: http://medicine.yale.edu/news/article.aspx?id=1060)

Anti-CTLA4 therapy-induced autoimmune disease

Cytotoxic T Lymphocyte- associated antigen 4 (CTLA-4) acts as a negative regulator of immune responses and affects T cell tolerance in humans. Antibodies that block CTLA4 have been approved for treatment of patients with metastatic melanoma, however these therapies also induce autoimmunity that affects a variety of organ systems including the GI tract, liver, skin, and endocrine function. Our lab is using a humanized mouse model to study anti-CTLA4-induced autoimmunity and its effect on different cell subsets and organs.

Clinical trials

Anti-CD3 mAb (Teplizumab) for prevention of diabetes in relatives at risk for T1DM (http://www.diabetestrialnet.org/ACD3/

T1DM immunotherapy using ex vivo expanded human autologous T regulatory cells (http://clinicaltrials.gov/show/NCT01210664)