Research Departments & Organizations
The work in our laboratory involves translational studies in human immunology, focused on Type 1 diabetes. We are carrying out clinical studies of new immune therapies, in particular humanized anti-CD3 monoclonal antibody, and study the metabolic and immunologic effects of these interventions on the disease process. We are studying the ability of this intervention to prevent the loss of insulin production that characterizes the disease and determining the optimal approach to use this and other immune treatments in the disease setting. We have identified a novel regulatory mechanism that we believe is involved in the patients’ response to anti-CD3 mAb and plan to expand these studies so that adoptive immune therapy can be performed without the need for systemic treatment of patients.
In addition, we are interested in developing new ways in which immune therapies can be combined with cellular and/or metabolic approaches to restore normal beta cell mass and function. We are testing whether immune interventions can lead to spontaneous restoration of beta cell mass and developing new approaches to stimulate beta cell regeneration. Our studies to address this goal involve studies in patients and in animal models of the disease.
Specialized Terms: Type 1 diabetes; Immune therapy; Autoimmunity
Extensive Research Description
The pathogenesis and treatment of autoimmune disease, in particular Type 1 diabetes.
Studies involve clinical trials with patients and investigations of the mechanism of action of immune therapies and the pathogenesis of disease in patients as well as in animal models when needed to address what cannot be studies in humans. Over the past 7 years, our lab has carried out trials of a humanized non-FcR binding anti-CD3 monoclonal antibody in patients and has studied the mechanism of drug action. These clinical studies have suggested novel mechanisms of immune regulation that are now to be addressed with new clinical studies.
|Diabetes Mellitus - Type 1||Hydroxychloroquine in Individuals At-risk for Type 1 Diabetes Mellitus (TN-22)|
|Diseases of the Nervous System||Imaging pancreatic beta-cells with PET neuroimaging agent 11C-PHNO|
|Diabetes Mellitus - Type 1, Diseases of the Endocrine System, Diseases of the Nervous System||Impact of Hypoglycemia on Brain Ketone and Neurotransmitter Metabolism in Type 1 DM|
|Children's Health, Diabetes Mellitus - Type 1, Diseases of the Endocrine System||Pathway to Prevention Study|
|Diabetes Mellitus - Type 1, Diseases of the Endocrine System||T1DM Immunotherapy Using Polyclonal Tregs + IL-2 (TILT)|
|Children's Health, Diabetes Mellitus - Type 1||Type 1 Diabetes Extension Study (T1DES)|
|Children's Health, Diabetes Mellitus - Type 1, Diseases of the Endocrine System||CTLA4-Ig (Abatacept)for Prevention of Abnormal Glucose Tolerance and Diabetes in Relatives At -Risk for Type 1|
Synergistic reversal of type 1 diabetes in NOD mice with anti-CD3 and interleukin-1 blockade: evidence of improved immune regulation.
Ablamunits V, Henegariu O, Hansen JB, Opare-Addo L, Preston-Hurlburt P, Santamaria P, Mandrup-Poulsen T, Herold KC. Synergistic reversal of type 1 diabetes in NOD mice with anti-CD3 and interleukin-1 blockade: evidence of improved immune regulation. Diabetes 2012, 61:145-54. 2012
Detection of β cell death in diabetes using differentially methylated circulating DNA.
Akirav EM, Lebastchi J, Galvan EM, Henegariu O, Akirav M, Ablamunits V, Lizardi PM, Herold KC. Detection of β cell death in diabetes using differentially methylated circulating DNA. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108:19018-23. 2011