The Departmental Roadmap

II. Overview of Basic Research Activities

Major Research Programs

Since its inception, basic research in the Department of Genetics and Genomic Sciences has focused on four main themes: 1) studies of inherited metabolic diseases, 2) generation and characterization of animal models of human genetic diseases, 3) genomics and gene discovery, and 4) treatment of genetic diseases. Our faculty has had substantial success in each of these areas (see attached list of "Departmental Firsts"). For example, using biochemical and molecular genetic technology, our faculty have cloned the genes encoding six lysosomal enzymes and five of the nine genes for heme biosynthesis, identified causative mutations in human patients with various genetic diseases, developed methods to efficiently produce their recombinant proteins, and made transgenic and knock-out/knock-in mice to evaluate various therapeutic modalities. Our successful development and evaluation of enzyme therapy for Fabry disease, approved in Europe in 2001 and by the FDA in 2003, exemplifies our ability to translate basic research into clinical practice. Moreover, our efforts to develop and evaluate novel therapeutic strategies have resulted in a translational pipeline, including current preclinical and clinical studies of enzyme replacement, pharmacologic chaperones, and gene transfer for specific genetic diseases. We also have developed partnerships with the private sector based on our basic research discoveries, and licensed our intellectual property for the development and clinical evaluation of new therapies. These include a long-term partnership with the Genzyme Corporation and the recent founding of a new biopharmaceutical company, Amicus Therapeutics.

During the last decade, our faculty also has been successful in using genomics and gene discovery technology. Using positional cloning strategies we have mapped the disease loci for 14 diseases and identified the causative genes in 12 of these disorders. Efforts to understand the pathophysiology of these disorders is being studied in mouse models, and therapeutic endeavors for several diseases are currently under development. In addition, new molecular-based diagnostic tests have been developed for these diseases. However, despite these successes, we also recognize the need to expand in the area of genomics and gene discovery, particularly in the identification of the causative or predisposing/susceptibility genes for common diseases (see below).

The Roadmap Committee reviewed our current strengths and limitations, and in particular our strengths of translating basic research into clinically relevant diagnostics and therapeutics. The Committee made a series of recommendations for the recruitment of new faculty and the initiation of new themes to advance our current efforts in view of current research trends and the NIH Roadmap. These recommendations are presented below.