Oberholzer, Jose , MD
Generation of an unlimited source of insulin producing beta cells for transplant
General Research Subject: Type 1 Diabetes
Focus: Islet Biology, Islet Biology\Beta Cell Growth and Differentiation, Stem Cell Research\Human\Adult, Transplantation
Type of Grant: Minority Undergraduate Internship
Project Start Date: January 1, 2013
Project End Date: December 31, 2013
Diabetes Type: Type 1 diabetes
In the U.S. over 39 million people suffer from diabetes, disease associated with risk of chronic health problems. Specifically 1 diabetes results from an autoimmune destruction of the insulin producing cells. Islet cell transplantation offers the promise of a cell-based, functional cure for diabetes. Transplanted islet cells quickly act as insulin factories, allowing recipients to live insulin free. The research in Dr. Oberholzer's Lab at the UIC is focused on overcoming the remaining obstacles to islet transplantation centering on 1) finding an unlimited source of insulin producing cells, through adult beta-cell proliferation and beta-cell regeneration; and 2) protecting the islet cells with microencapsulation to avoid the long-term risks of immunosuppressant drugs.
The proposed research offers a one-year internship to an underrepresented undergraduate in order to provide necessary academic preparation and skills in different diabetes-related biomedical research techniques, covering both clinical and basic scientific investigation. Working alongside researchers at the bench, the student will learn about the design and completion of a successful research project. The intern will develop critical scientific thinking focused on the development of beta-cell replacement therapies for transplant, with the final goal being a cure for diabetes. Furthermore the diverse scientific environment of our lab, and the proximity to MDs, PhD student's, postdocs, and faculty members, will provide him with an academic vision that will translate into a broadening of his choices in the pursuit of more advanced degrees in biomedical and clinical sciences, and develop a superior level of commitment within the field of diabetes research.
Mentor: Jose Oberholzer Undergraduate: Andre Thomas, Jr.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating, and curing diabetes?
Type 1 diabetes results from an autoimmune destruction of insulin producing cells. Replacement of insulin producing cells and the control of autoimmunity and allorejection are two areas where beta-cell replacement therapy and Islet cell transplantation offer promise for a cell-based, functional cure for diabetes. Transplanted islet cells quickly begin to act as insulin factories, allowing recipients to live insulin free.
The research in Dr. Oberholzer's Lab at the UIC is focused on overcoming the remaining obstacles to islet transplantation with a unique program focused on 1) finding an unlimited source of insulin producing cells through adult beta-cell proliferation and beta-cell regeneration; and 2) protecting the islet cells with microencapsulation to avoid the long-term risks of immunosuppressant drugs.
The particular project that the intern will be involved with will be focused on the investigation of new sources for beta-cell progenitors and optimization of the proliferation of existing adult beta-cells through the over expression of cell cycle molecules. Using methods compatible with clinical use, these potential beta-cell progenitors can be routinely isolated in large numbers from a CD133+ cell population derived from exocrine tissue, and are capable of generating insulin producing cell sources of Ngn3+ progenitor cells for Type 1 Diabetes therapies. Developing strategies for the differentiation of these precursor cells into insulin secreting cells will be one of the intern's main research focuses.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
Our philosophy is to make a functional cure for diabetes available to everybody. The main challenge right now is that we can only perform islet cell transplantation for a limited patient population. The devastating effects of hypoglycemia unawareness have important effects on the quality of life of many Type 1 diabetic patients. The only way to treat them is through pancreatic or islet cell transplant. Currently the limited amount of organ donors and the challenges of immunosuppressive drugs, excludes children, the obese, as well as patients with very high insulin requirements. Islet cell transplantation is still an experimental procedure and can be only offered within the framework of a clinical trial. At the UIC we are approaching the end of Phase 3 Clinical trials.
Our research focuses on two problems critical to the treatment of diabetes. 1.To obtain an unlimited number of insulin producing cells in the laboratory, that are suitable and safe for transplantation into humans. 2. The enclosure of these cells in biocompatible microcapsules in order to prevent rejection, and thereby eliminating the need for chronic, systemic, immunosuppressive drugs. The success of this research will provide millions of patients a chance to live a normal and healthy life, free of the complications of diabetes.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your efforts?
Among the racial and ethnic minority populations in the United States, African Americans are one the groups particularly susceptible to Diabetes, for whom the age of onset for both Type 1- and Type 2-Diabetes has decreased. Specifically, Type 1 diabetes (T1D) is now one of the most common pediatric chronic illnesses, affecting 1 in 500 children, with the highest rate of newly diagnosed cases occurring in the African American population. This one-year internship will allow me to gain exceptional experience in the treatment of this devastating disease that is particularly affecting my community. Being involved in diabetes research will help me to gain a better understanding of diabetes, and to raise awareness. I have always had a strong desire to be part of this research, and to be part of this journey that can offer the hope of a cure among diabetic people.
In what direction do you see the future of diabetes research going?
For Type 1 Diabetes, replacing the insulin producing cells and controlling the autoimmunity and allorejection are two problems where beta-cell replacement therapy offers the promise of a cell-based "functional cure" for diabetes.
Future research will be centered on providing an unlimited source of insulin producing cells, in combination with encapsulation, that will allow treatment for those more vulnerable pediatric patients. The incidence of Type 1 diabetes in young children is increasing worldwide and is predicted to continue to increase in future years. Encapsulation of islet cells will allow cells to sense glucose and secrete insulin while protecting them from the attack by the body's immune system. Moreover, the advances in beta-cell proliferation research will open the possibility for inducing replication in the remaining beta-cells of diabetics. All this, together with the research on new islet cell formation from progenitors within the pancreas, provide the most attractive therapies for diabetes. In vitro evaluation and rigorous research, and their translation from the bench to the bed side, are critical for offering this promising therapy to our diabetic patients.
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