Studies are being conducted on several genetically transmitted diseases, such as xeroderma pigmentosum, that are associated with defective mechanisms for repair of damaged DNA and a markedly increased incidence of cancer. These studies have recently been extended to analysis of the neurological disorders amyotrophic lateral sclerosis and Alzheimer's disease. Chromosome III of the yeast, Saccharomyces cerevisiae, is being used as a model to study the replication and segregation of eukaryotic chromosomes. Current areas of study include structure-function analysis of replication origins, regulation of origin activity, contribution of individual replication origins to chromosome stability, and structure of replication fork barriers. Various aspects of cellular and molecular immunology are being studied through research projects that dissect the host-tumor interactions involved in an experimental lymphoma model.
Research is conducted in the fields of autoimmunity and malignancy.
Emphasis is on the study of a subpopulation of B cells, B-1 cells, that are elevated in certain autoimmune disorders and are the malignant cells in chronic lymphocytic leukemia. Such mutations are intimately involved in the production of many cancers. Combined in vivo and in vitro approaches, primarily in prokaryotic systems, have enabled descriptions of the most frequent mutational events in terms of DNA sequence preferences of the enzymes involved in mutagenesis. These biochemical descriptions are beginning to be applied to the analysis of spontaneous mutant sequences arising in human patients to try to identify major enzymatic contributors to germline and somatic mutations. The laboratory is concerned with the study of oncogene expression in leukemic cells and mechanisms by which chemical compounds and vitamin D inhibit DNA replication and induce differentiation of leukemic and breast cancer cells.