- Postdoctoral Fellow, Neuroscience, Duke University, 1996-2001
- PhD, Molecular Cancer Biology, Duke University, 1995
- BS, Cell and Molecular Biology, University of Michigan, 1989
My lab started in 2004 with a primary research focus on the regulation of genes involved in nerve growth and regeneration. While this continues to be an active area of research in the lab, the scope of our research has expanded into new and related areas based on the interests and discoveries of graduate students and staff who have been part of my research team over the years. In all of our projects we have mainly used zebrafish as a model system because the optical clarity and accessibility of the developing embryos make them amenable to visualizing early developmental events in the context of living vertebrate embryos. The adult zebrafish also serve as an ideal model for our regeneration studies since, unlike mammals, they are capable of functional regeneration after central nervous system (CNS) injury. More recently we have added mouse models for comparative studies in some of our projects. Current areas of study in the lab include:
- Regulation of axon growth gene expression during successful CNS regeneration. In humans, damage to axonal tracts within the adult central nervous system (CNS) results in permanent loss of function due to the failure of mature neurons in the brain and retina to support regenerative axon growth. In contrast, teleost fish re-establish CNS growth capacity and functionally recover from CNS injury. Thus, what appears to set fish apart is the ability to reinitiate and sustain the expression of axon growth-associated proteins, such as growth-associated protein 43 (GAP-43), in response to CNS injury. GAP-43 is one of the most abundant proteins in axonal growth cones and functions in axon growth and guidance by regulating cytoskeletal components in response to local signaling events in the growth cone. Clarifying the transcriptional mechanisms that underlie this re-expression of growth-promoting genes is critical to understand and potentially recapitulate successful regeneration in the mammalian CNS. The goal of this research is to elucidate the transcriptional regulatory mechanisms that are necessary to initiate and sustain successful vertebrate CNS axon regeneration, which underlie functional CNS recovery after injury.
- Translating environmental guidance cues to cytoskeletal changes in growing axons by GAP-43 phosphorylation.
- Regulation of neural crest migration and differentiation by CABIN1. Craniofacial anomalies are leading causes of infant morbidity and mortality, and are characteristic of pediatric syndromes associated with deletions in the 22q11.2 band on chromosome 22. We have recently discovered that reduced expression of calcineurin-binding protein 1 (CABIN1), a gene located on 22q11.2, results in craniofacial abnormalities in developing zebrafish. Furthermore, a reduction in CABIN1 expression in zebrafish leads to a wide array of other congenital defects also observed in children with 22q11.2 deletions. Many of the congenital defects associated with 22q11.2 deletions stem from improper development of the cranial neural crest, a multipotent embryonic stem cell population that emigrates from dorsal neural tube to form several tissues including the cartilage, bones, and connective tissues of the head and neck. The goal of this research is to elucidate how CABIN1 functions in normal craniofacial development in order to deduce how reduced CABIN1 expression in patients with deletions in distal 22q11.2 may contribute to craniofacial defects.
- Transgenic reporter fish as indicators of environmental stressors.