608-265-6446 (office); 608-265-6301 (lab)
4157 WI Institute Medical Research
BS/BA, 1984, Biochemistry and Anthropology, University of Vermont
PhD, 1989, Pharmacology, University of Michigan at Ann Arbor
Postdoctoral Research, 1994, National Institutes of Health, NIDDK, Bethesda, MD
Professor of Cell and Regenerative Biology
We use multidisciplinary approaches to understand stem/progenitor cell function, blood cell development, and vascular biology. Such approaches include genomics, proteomics, chemical genetics, embryonic stem cell differentiation, computational analysis, and traditional methodologies.
In addition to elucidating biological principles, we aim to develop innovative therapeutic strategies based on targeting novel mechanisms. Projects relevant to stem cell biology/regenerative medicine include:
- Mechanisms of hematopoiesis: We are analyzing the function/regulation of GATA factors that control hematopoietic stem cells (HSCs) and hematopoiesis. Transcriptional profiling and ChIPchip analysis have identified a cohort of novel GATA factor target genes, including genes encoding proteins that bear no obvious similarity to known proteins. Loss-of-function and gain-of-function studies are being conducted in mice, zebrafish, human adult stem/progenitors, and embryonic stem cell systems to discover new modes of controlling stem/progenitor cell function and to devise novel applications towards translational medicine. Defining novel hematopoietic mechanisms has enormous importance, as deviations from physiological programs yield leukemias, lymphomas, myelodysplasia, and additional blood disorders.
- Vascular mechanisms and engineering: We have developed a novel murine model characterized by severe hematopoietic stem/progenitor cell depletion and a severe vascular integrity defect. We are dissecting mechanisms underlying the establishment and maintenance of vascular integrity in normal and disease states. Understanding such mechanisms is essential for developing efficient approaches to promote the vascularization of engineered tissues, a limiting factor in regenerative medicine.