The Departmental Roadmap

II. Overview of Basic Research Activities

Recommendations for Basic Research

1. Focus on Neurodegenerative Diseases
2. Genomics and Gene Discovery
3. Parmacogenetics
4. Cutting Edge Research Themes

1. Focus on Neurodegenerative Diseases

Many inborn errors of metabolism have severe and debilitating CNS disease, but the underlying pathophysiology of the neurologic involvement in these disorders is poorly understood. Such understanding would guide the development of new therapeutics to treat these diseases. While our Department has been extremely successful in the study of metabolic disorders and has created several mouse models with neurological phenotypes similar to their human counterparts, additional expertise in neurobiology and CNS therapy is needed to advance studies of neurological pathogenesis and facilitate the development of effective CNS-directed therapies. Such recruitment should recognize the neurobiology strengths in other Departments and should recruit expert faculty who would complement existing Sinai expertise. This is an important direction for our future research in this era of neurobiology.

Thus, the Roadmap Committee recommends that a major, new research direction be focused on the investigation of brain disease in inherited metabolic diseases, and the development and evaluation of new CNS-directed therapeutic strategies for these disorders. For example, such therapeutic strategies may include: intracranial stem cell transplantation, gene therapy, and the development of small molecule therapeutics, such as pharmacologic chaperones. To accomplish these goals, the Committee recommends recruitment of a faculty member with expertise in neurogenetics and/or neuroscience, with the expectation that such an individual would bring a unique and independent research program to the Department. Clearly, such an individual would also augment the substantial strengths in neurosciences and neurodegenerative disease that already exists at Mount Sinai. While the specific research program of such a faculty recruit may span several areas, it is essential that s/he have a strong background in neuroscience and animal models, and be willing to actively participate in ongoing Departmental and Institutional research programs.

2. Genomics and Gene Discovery

Although our past efforts in the identification of disease genes have focused primarily on Mendelian disorders, the Committee recognizes that we are at a unique moment in history since the genomes of man and a variety of model organisms have been sequenced, and novel expression assays and proteomics techniques have been developed, providing the tools needed for the genetic analysis of common disorders. Clearly, the genetic analysis of such complex traits will represent a major research focus in Genetics and Genomic Sciences in the 21st century. Thus, it is important to advance our capabilities in the area of complex traits.

The Departmental Roadmap Committee recommends that our gene discovery program be augmented by new faculty in the area of genetic epidemiology. Genetic epidemiologists are essential for the gene discovery efforts in the Department, as well as in the Institution. Thus, this is a high priority for immediate recruitment. Genetic epidemiologists are needed to provide the necessary expertise in computational biology required for the genetic analysis of complex disorders. The Roadmap Committee recommends that a search committee be established immediately to recruit a team of two genetic epidemiologist/statisticians (previously called population geneticists), a senior, more experienced investigator who is theoretical and can design novel methodologies, and a second investigator who would provide service to Institutional investigators.

3. Pharmacogenetics

Pharmacogenetics refers to common genetic variations that alter drug metabolism. This is a rapidly expanding field that has been dramatically bolstered by the Human Genome Project and new molecular technologies, and has recently become a major focus of research in the public and private sectors. In fact, this area represents a rich opportunity for the Departmental Faculty to interact with Clinical Faculty throughout the Institution in order to identify and develop assays for commonly used drugs that will be of particular value to the patient populations served by Mount Sinai. Therefore, the Roadmap Committee recommends that an expert, senior (if possible) pharmacogeneticist be recruited to establish a research and clinical program in the Department. Such an individual may be studying the genetics of drug metabolism in cancer, cardiovascular and/or neurodegenerative diseases, since these represent important areas of strength at Mount Sinai with large, ongoing clinical and basic research programs. Also, it is well recognized that aging individuals require special consideration in drug dose. Thus, the geriatric community may be an important target for such research and clinical studies. Such an individual would clearly add a new dimension to our Department, but also could augment many existing research programs throughout the Institution.

4. Cutting Edge Research Themes

The field of genetics and genomics is rapidly advancing and new areas of research are always being uncovered. In particular, translational areas such as reproductive genetics and molecular cytogenetics, as well as the rapidly growing and important field of epigenetics, promise to be important research themes over the next five years. Therefore, the Committee recommends that the Department carefully monitor developments in these areas and, if resources become available, recruit around these themes.