Research activities available for predoctoral and postdoctoral trainees in the Department of Genetics and Genomic Sciences include basic and applied studies in: 1) Molecular Genetics, 2) Gene Therapy, 3) Biochemical Genetics, 4) Cytogenetics, 5) Somatic Cell Genetics, 6) Gene Discovery and Gene Mapping, 7) Immunogenetics and 8) Clinical Genetics. Current studies in each of these areas are listed below. It should be noted that research projects are undertaken as team efforts; typically, each project involves a faculty member, postdoctoral fellow, predoctoral student and/or a technician. In this way, graduate students and postdoctoral fellows are maximally exposed to a variety of experimental procedures, technical skills and scientific interactions.

  1. Molecular Genetics
    1. Isolation and characterization of full-length cDNA and genomic sequences encoding gene products relevant to inherited metabolic diseases (e.g. the specific enzymes responsible for sideroblastic anemia, the porphyrias and lysosomal storage diseases).
    2. Investigation of the molecular defects in these metabolic diseases using a variety of techniques including gene amplification, automated genotyping, automated dot blot hybridization with allele-specific oligonucleotides and double-stranded sequencing. Development of molecular diagnostic assays for identification of affected individuals, carriers and for prenatal diagnosis.
    3. Use of prokaryotic and eukaryotic expression systems for the large scale production of human gene products, for studies of site-specific mutagenesis, and for kinetic and structural characterization of the normal and mutant proteins, including crystallography.
    4. Studies of the control and regulation of gene expression for tissue-specific and housekeeping genes.
    5. Construction and characterization of "knock-out" models of genetic disease.
    6. Identification of novel genes involved in programmed cell death by mRNA differential display of apoptotic cells.
    7. Use of prokaryotic and eukaryotic expression systems for the large scale production of human gene products, for studies of site-specific mutagenesis, and for kinetic and structural characterization of the normal and mutant proteins.
    8. Studies of the control and regulation of gene expression for tissue-specific and housekeeping genes.
  2. Enzyme and Gene Therapy
    1. Studies of enzyme and cellular strategies for the treatment of genetic diseases including enzyme replacement, enzyme manipulation by cofactor supplementation, enzyme engineering by site directed mutagenesis, or allotransplantation in appropriately selected diseases.
    2. Construction of retroviral vectors and use of retroviral-mediated gene transfer for in vitro metabolic correction of various genetic disorders.
    3. In vivo gene therapy evaluation using animal models.
    4. Development of new viral and non-viral gene transfer vectors.
    5. Development of novel fluorescence-based methods for the selection of metabolically corrected cells following gene delivery.
    6. Development of gene delivery systems for the CNS.
  3. Biochemical Genetics
    1. Kinetic, structural and immunologic characterization of the defective gene products in cells and tissues from patients with metabolic diseases.
    2. Identification and/or characterization of the enzyme defects in newly identified or ill-defined disorders and characterization of their molecular pathology.
    3. Characterization of animal analogues of human metabolic diseases and use of these model systems for the development and evaluation of new therapeutic strategies.
  4. Cytogenetics
    1. Chromosomal abnormalities: Use of chromosome elongation (late prophase preparations) and newer banding techniques to characterize structural alterations in chromosomes of parents with congenital malformation syndromes and in couples with infertility/recurrent miscarriages.
    2. Chromosome breakage/instability syndromes: Studies of chromosome breakage (determination of in vitro and in vivo effects of various drugs; studies of sister chromatid exchanges.
    3. Cytogenetics and prenatal diagnosis: Establishment of methods for improved banding of metaphase preparations for chorionic villi biopsies.
    4. Use of molecular and cytogenetic techniques such as in situ hybridization, and/or FISH for refined diagnosis and mapping of genetic loci.
    5. The role of methylation in chromosome structure and imprinting.
  5. Somatic Cell Genetics
    1. Characterization of the expression of differentiated functions (temporal, tissue specific) by somatic cell hybridization studies.
    2. Studies of the mechanism of X-chromosomal inactivation.
    3. Use of somatic cell genetic techniques for the production of monoclonal antibodies.
  6. Gene Discovery and Gene Mapping
    1. Linkage analysis to assign disease genes to specific chromosomal regions.
    2. Gene mapping using somatic cell hybridization techniques, pulsed-field electrophoresis, in situ hybridization.
    3. YAC cloning; configuration alignment, automated sequencing.
    4. Positional cloning of Mendelian diseases and complex traits.
  7. Immunogenetics
    1. Use of the "hybridoma" technique for the production of monoclonal antibodies to specific antigens/epitopes.
    2. Immunologic characterization of the molecular architecture of mutant proteins by the use of monoclonal antibody panels.
    3. Studies of HLA haplotype-disease associations.
  8. Clinical Genetics/Prenatal Diagnosis
    1. Application of genetic technology to the diagnosis, management and treatment of patients and families with genetic disease.
    2. Delineation of new syndromes.
    3. Genetic counseling methodology and assessment.
    4. Prenatal genetics: Studies designed to develop new and improved methods for the prenatal diagnosis and/or treatment of chromosomal, biochemical or multifactorial disorders. Evaluation of chorionic villi sampling (CVS) for first trimester prenatal diagnoses of chromosomal and metabolic disorders. Application of molecular diagnostic techniques for precise diagnosis of disorders whose genes are expressed in specific tissues. Use of ultrasound, fetoscopy and fetal blood aspiration for the prenatal diagnosis of birth defects.
    5. Treatment of genetic diseases: Currently evaluating enzyme replacement in clinical trials for Gaucher disease and Fabry disease.
    6. Population screening of common genetic diseases: Investigation of effective methods of delivering DNA-based prenatal and presymptomatic genetic testing to the general population.
    7. Evaluation of the Prediction/Prevention paradigms for genetic diseases.