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May 2009

Researcher's visit to ISMETT

Visit to ISMETT
Dr. Giannoukakis (left) and Dr. Trucco (right)

The Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT) is a joint public-private partnership between the Region of Sicily, through Civico and Cervello hospitals in Palermo, and UPMC. Over the past decade, ISMETT has become one of the leading organ transplant centers in Europe and a major referral center for other Mediterranean countries. 

Nick Giannoukakis, PhD, associate professor of pathology and immunology, University of Pittsburgh School of Medicine, and Massimo Trucco, MD, director of the Division of Immunogenetics at Children’s Hospital of Pittsburgh of UPMC, and director of the ISMETT GMP “cell factory” facility, visited ISMETT to discuss the clinical and basic research studies in progress and planned at the University of Pittsburgh School of Medicine. These studies target autoimmunity with gene-modified cells and novel delivery vectors.

Type 1 diabetes, a disease in which T cells destroy a person’s insulin-producing cells in the pancreas, resulting in high blood sugar, has been prevented and reversed successfully in mice using dendritic cells engineered to reprogram the immune system. This approach is in phase 1 studies in Pittsburgh, and the data suggest that the technique soon may be applied to safely treat patients with type 1 diabetes when they are first diagnosed. At the same time, the approach has been simplified into a microsphere “vaccine” and is being codeveloped with Baxter Healthcare. The clinical studies are supported by a number of basic research studies focusing on the mechanisms by which the dendritic cells and the microspheres induce immune system reprogramming, the cells with which they interact in the body in the process, and the molecular pathways that are modified. Dr. Giannoukakis took time to talk with us regarding his visit.
           
International Extra (IE): ISMETT is strongly focused on research. Are there fields of mutual interest and collaboration that may be pursued jointly, or are already being pursued, by your group and the Palermo group?            
Dr. Giannoukakis: Absolutely. The commitment  ISMETT to basic and applied research to complement its clinical focus is very attractive, especially as we transfer our protocols. One center does not necessarily have the world’s expertise in everything. Independent replication of research is gold standard of any scientific endeavor. The dedication of ISMETT scientists and their incredible sophistication ensures they will be at the forefront of discovery in collaborative basic research projects as well as in the validation of and replication of critical and preclinical models. We envision fruitful collaboration in the realm of immunotherapy for and in the field of vaccine development for immunoregulation to promote and autoimmune disease prevention and reversal.
           
IE: What are the main scientific areas of interest for your group?          
Dr. Giannoukakis:
Our main research focus is to use genes and cells as drugs and medicines by which autoimmunity can be prevented or controlled. Broadly defined, autoimmunity refers to the phenomenon where a person’s immune system begins to react against particular cells and tissues, leading to a disease state. One such example is type 1 diabetes mellitus where the body’s immune cells seek out and eventually destroy the insulin-producing cells of the pancreas. Many interdisciplinary projects are ongoing in my team to harness the potential of stem cells, viral and nonviral gene delivery vehicles, insulin-producing cell transplants, and vaccine approaches to prevent type 1 diabetes and to restore insulin production.
           
Additionally, my group is engaged in the genomic and proteomic discovery of immune cell molecules that can be manipulated to induce the regulation of the cells that promote inflammation in type 1 diabetes. Key to this is an understanding of the genetic and epigenetic regulation of such genes and the proteins that control their expression. Among our specific ongoing projects, we are developing cell and particle vaccines to prevent 1 diabetes; replication-defective viruses as which insulin cell transplants can be engineered to resist immune rejection in diabetic recipients; proteomics discovery of dendritic cell and T cell markers of regulatory immune cell subsets; discovery of type 1 diabetes susceptibility genes through systems biology approaches (proteomics and genomics); human embryonic stem cells as renewable sources of regulatory immune cells and insulin-producing cell surrogates; and studies on the epigenetic regulation of immunomodulatory molecules.
           
IE: During your time at ISMETT, you had the chance to visit the clinical facility and the cell production GMP facility. What did you think?
Dr. Giannoukakis:
The facilities are state-of-the-art and mirror the excellence offered in Pittsburgh. Indeed, I felt like I was still in Pittsburgh. The GMP facility, which I firmly believe is one of the features that makes ISMETT stand out as a state-of-the-art European facility, will be critical in expanding clinical studies and in placing ISMETT among a unique tier of clinical and research centers in the world. It is exceptionally well-designed, and it is obvious that careful and thoughtful planning went into its design and its logistics.

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