Our lab is focused on the development of HIV-1 vectors for gene therapy of genetic disease. In addition, we are using the vector system to study HIV-1 biology. We are also interested in utilizing the HIV-1 vector system for functional genomics.
My research aims at prevention and treatment of cardiovascular diseases and focuses on the identification of genes that confer susceptibility or resistance to the diseases with the use of genetically engineered mice. In collaboration with Dr.Oliver Smithies, I very recently developed a new method for altering gene expression by modifying 3’ untranslated regions in mice which enables fine-tuned modification of gene expression. I am now analyzing the phenotypes of several mouse models generated with this method.
Topic 1 We seek genomic targets for carcinogenesis among segments of DNA replicated in early S phase when cells are most susceptible to carcinogens. We are mapping genomic sites replicated during early S phase, identifying origins of replication activated in this interval, and characterizing temporal sequencing of replication from these origins. Topic 2 We are reconstructing differentiated and functional human endometrial tissue from epithelial and stromal cells interacting in culture. We use these co-cultures to study development of endometrial cancer.
Research in the Kaufmann laboratory is concerned with determining the mechanisms whereby cell cycle checkpoints suppress human cancer development. We are focused on two checkpoints that help to stabilize the genome. The decatenation G2 checkpoint delays mitosis until daughter chromatids are sufficiently disentangled by topoisomerase II. This checkpoint is regulated by the breast cancer susceptibility gene BRCA1. The intra-S checkpoint regulates DNA synthesis by controlling the rates of replicon initiation and DNA chain elongation. This checkpoint is regulated by two proteins, Timeless and Tipin, that mediate signaling at stalled replication forks. A program project is studying how the Timeless-Tipin replication fork protection complex protects against UV-induced chromosomal damage and sunlight-induced melanoma.
My lab studies the pathogenic mechanisms of two bacterial pathogens, Haemophilus ducreyi and Francisella tularensis. H. ducreryi, the agent of the sexually transmitted infection chancroid, somehow inhibits the development of an effective immune response
Our research focuses on the structure and function of medically important proteins from the crystallographic approach. The current topics include cycolphilin, calcineurin, heat shock protein 90 (hsp90), and cyclic nucleotide phosphodiesterase.
Hormones influence virtually every aspect of plant growth and development. My lab is examining the molecular mechanisms
controlling the biosynthesis and signal transduction of the
phytohormones cytokinin and ethylene, and the roles that these hormones play in various aspects of development. We employ genetic, molecular, biochemical, and genomic approaches using the model species Arabidopsis to elucidate these pathways.
I am interested in the comparative biomechanics of marine invertebrates. In particular, I study the functional morphology of musculoskeletal systems, the structure, function, development and evolution of muscle, and invertebrate zoology, with particular emphasis on the biology of cephalopod molluscs (octopus and squid). My research is conducted at a variety of levels and integrates the range from the behavior of the entire animal to the ultrastructure and biochemistry of its tissues.
Our research explores the role of hypoxia-inducible factor (HIF) in tumorigenesis. HIF is a transcription factor that plays a key role in oxygen sensing, the adaptation to hypoxia and the tumor microenvironment. It is expressed in the majority of solid tumors and correlates with poor clinical outcome. Therefore, HIF is a likely promoter of solid tumor growth and angiogenesis. Our lab uses mouse models to ask if and how HIF cooperates with other oncogenic events in cancer. We are currently investigating HIF’s role in the upregulation of circulating tumor cells and circulating endothelial cells.
Our focus is on using genetic methods to improve transplantation using ES and hematopoietic stem cells in transplant models. A second focus of the lab uses mutant mice to examine potential drug targets for ameliorating radiation-induced lung damage.
We have used gene targeting to generate an animal model for the most common genetic disease in the Caucasian population, cystic fibrosis. We are continuing to characterize this animal and to modify it to produce a disease that more closely resembles human cystic fibrosis. A second area in which our lab is interested involves the study of the inflammatory processes involved in allergic responses, asthma, and arthritis. Our current efforts are aimed at generating animals deficient in various factors that are believed to be important in these diseases. By providing us with a better understanding of the immunological processes that underlie allergic responses, asthma and arthritis, these animals should help us to identify more effective treatments for these diseases.
I study a canine model of Duchenne muscular dystrophy. Both conditions occur due to mutations in the dystrophin gene. Our research has defined clinical and pathologic features to better understand disease pathogenesis and to assess treatment.
We use a combination of experimental and computational methods to redesign protein-protein interactions. The potential applications for this technology include enhancing protein therapeutic and creating new tools to study signaling pathways.
