Liu, Chih-Pin , PhD
Tolerance induction and inhibition of T1D
General Research Subject: Type 1 Diabetes
Focus: Immunology, Transplantation
Type of Grant: Basic Science
Project Start Date: January 1, 2011
Project End Date: December 31, 2013
Diabetes Type: Type 1 diabetes
Funded by The Steven Gordon Family Foundation
Much current research has been dedicated to the development of novel approaches to control or inhibit type 1 diabetes (T1D). Albeit promising in animal models, the translation of these potential treatments requires extensive metabolic and toxicity testing in pre-clinical studies and clinical trials, which may delay the use of these drugs for years. There is a critical need to find a more effective and less costly manner to expedite the 'bench-to-bedside' translation of novel therapies. One answer is to identify novel uses for drugs already approved by the FDA and investigate their potential use in the treatment of T1D. This would save significant time, effort and costs, as much of the FDA-required testing would not be needed or would be significantly reduced. The goal of the proposed studies is to investigate the innovative use of one such FDA-approved drug that has traditionally been used to treat leukemia. Preliminary research in our laboratory has demonstrated this drug may hold great promise in controlling the autoimmunity leading to T1D. We propose to determine whether this drug is able to not only prevent but also treat T1D in an animal model, to examine whether it can also be used to prevent islet graft rejection, and to elucidate its underlying immune modulation mechanisms. These studies will provide novel insights as to how this drug may induce tolerance that inhibits T1D. Should the drug prove successful for use with T1D, its well-studied toxicity and metabolic kinetics in humans will significantly accelerate its translation to clinical use.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
For type 1 diabetes patients, there is an urgent need to find an effective and safe therapy to cure the disease. To achieve that goal, it is necessary to maintain proper beta islet cell function through suppression of on-going islet cell inflammation, transplantation of insulin-producing cells, or regeneration of functional beta cells. It is known that the inability to maintain a balance between different T cell subsets can result in destructive autoimmunity and islet inflammation. Consequently, clinically relevant agents that induce effective immune tolerance by selectively affecting different T cell subsets are needed as an effective approach to treat human diabetes. Studies to understand how such an approach affect various T cell subsets will elucidate the mechanisms underlying tolerance induction and further improve therapeutic outcomes. The overall goals of the proposed studies are to perform studies to examine whether a FDA-approved drug for treating leukemia and skin diseases, can be used to inhibit T1D and prevent islet graft rejection, and to elucidate its underlying mechanisms of action.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
The knowledge gained from the proposed studies should help in the design of novel therapies that will induce stable immune tolerance in diabetic patients through rebalancing immune cells and controlling on-going inflammation in the islets. The chronic inflammation and long-term use of insulin may also cause complications that would compromise the quality of patients' daily life. These studies should also help identify new molecular and cellular targets that are useful for developing therapies for monitoring the disease progress, reducing severity of complications, and treatment for diabetic patients or patients receiving islet transplants.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Some of my close relatives and friends have diabetes. In addition, the number of patients with diabetes has been growing at an alarming rate in the U.S. and worldwide. I hope that our research would be able to help accelerate the design of novel therapies leading to a cure of this disease.
This award is critical for us to successfully perform our proposed studies that are designed to prevent and/or treat diabetes and to develop novel strategies to protect islet grafts from immune destruction.
In what direction do you see the future of diabetes research going?
In the field of type 1 diabetes, it is expected that more extensive research effort will be focused on developing effective and safe methods for inducing immune tolerance in diabetic patients and patients receiving insulin-producing cell transplantation. It is also necessary to develop animal models for the human disease in order to determine the in vivo cellular and molecular mechanisms underlying the induction of such immune tolerance.
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