William and Donna Acquavella Professor of Ophthalmic Sciences (in Ophthalmology and Pathology and Cell Biology) Administrative Titles Research Director, Edward S. Harkness Eye Institute Since the entire sequence of the human genome has become available, our goal is to use this information to assess the whole range of genetic variation in the human population. This will allow us to answer a myriad of questions, including the most immediate: Which genetic variants (or their combinations) predispose humans to different inherited disorders? Our laboratory focuses on discovering genetic defects underlying Mendelian and complex disorders with special emphasis on eye diseases. The first step in discovering the underlying mechanisms of a disorder is the cloning and characterization of the relevant gene(s) and determining the mutation spectrum, causative for each individual phenotype. This goal is achieved in our lab by systematic screening of candidate genes on large collections of patient DNA with semi-automated, high-throughput mutation detection and genotyping technologies. Among candidate genes under analysis, we are specifically interested in those that belong to the ATP-binding cassette (ABC) transporter superfamily. Members of this family are ubiquitous membrane proteins that carry out vital transport functions in all cells and cellular organelles. We have succeeded in defining several ABC genes as involved in various human inherited diseases (ABCR, ABC7) and in important cellular functions such as multi-drug resistance during cancer chemotherapy (ABCP). The discovery of ABCR, a rod photoreceptor-specific transporter of retinoids, has significantly advanced our knowledge of molecular genetic basis of several retinal diseases including Stargardt macular dystrophy (STGD), cone-rod dystrophy (CRD), retinitis pigmentosa (RP19), and age-related macular degeneration (AMD). Major research objectives of the laboratory are: (1) cloning and mutational analysis of genes involved in eye disorders of Mendelian inheritance; (2) association analysis of genetic variation in candidate genes for complex disorders, such as age-related macular degeneration (AMD); (3) development of microarray-based screening technologies and new approaches for ABC gene therapy. William and Donna Acquavella Professor of Ophthalmic Sciences (in Ophthalmology and Pathology and Cell Biology) Administrative Titles Research Director, Edward S. Harkness Eye Institute Since the entire sequence of the human genome has become available, our goal is to use this information to assess the whole range of genetic variation in the human population. This will allow us to answer a myriad of questions, including the most immediate: Which genetic variants (or their combinations) predispose humans to different inherited disorders? Our laboratory focuses on discovering genetic defects underlying Mendelian and complex disorders with special emphasis on eye diseases. The first step in discovering the underlying mechanisms of a disorder is the cloning and characterization of the relevant gene(s) and determining the mutation spectrum, causative for each individual phenotype. This goal is achieved in our lab by systematic screening of candidate genes on large collections of patient DNA with semi-automated, high-throughput mutation detection and genotyping technologies. Among candidate genes under analysis, we are specifically interested in those that belong to the ATP-binding cassette (ABC) transporter superfamily. Members of this family are ubiquitous membrane proteins that carry out vital transport functions in all cells and cellular organelles. We have succeeded in defining several ABC genes as involved in various human inherited diseases (ABCR, ABC7) and in important cellular functions such as multi-drug resistance during cancer chemotherapy (ABCP). The discovery of ABCR, a rod photoreceptor-specific transporter of retinoids, has significantly advanced our knowledge of molecular genetic basis of several retinal diseases including Stargardt macular dystrophy (STGD), cone-rod dystrophy (CRD), retinitis pigmentosa (RP19), and age-related macular degeneration (AMD). Major research objectives of the laboratory are: (1) cloning and mutational analysis of genes involved in eye disorders of Mendelian inheritance; (2) association analysis of genetic variation in candidate genes for complex disorders, such as age-related macular degeneration (AMD); (3) development of microarray-based screening technologies and new approaches for ABC gene therapy.

Major research objectives of the laboratory are: (1) cloning and mutational analysis of genes involved in eye disorders of Mendelian inheritance; (2) association analysis of genetic variation in candidate genes for complex disorders, such as age-related macular degeneration (AMD); (3) development of microarray-based screening technologies and new approaches for ABC gene therapy.