Person
Incardona, John P.
|
Biography and Research Interest
Research focus:
In the Pacific Northwest many marine and anadromous fish species utilize habitat for spawning or rearing adjacent to areas with intense human land use activities. Consequently, early life history stages (embryos and larvae) are potentially exposed to a vast array of chemical contaminants from urban and agricultural sources. We are utilizing zebrafish to begin to understand the impacts of common aquatic contaminants (e.g. pesticides, herbicides, metals, petroleum hydrocarbons) on fish development. Mechanistic insight gained from these studies will be translated into technologies for assessing thresholds of toxicity in local species of concern that are otherwise difficult to study in the lab (e.g. salmonids). These studies are aimed to address data gaps concerning the effects of anthropogenic contaminants on fish populations that are trust resources for NOAA Fisheries.
We focused initial studies on petroleum-derived polycyclic aromatic hydrocarbons (PAHs), ubiquitous contaminants associated with urbanization of the Puget Sound basin. Studies prompted by the Exxon Valdez oil spill in Prince William Sound, which contaminated spawning grounds for Pacific herring and pink salmon, identified a syndrome of edema, spinal curvature and craniofacial defects induced by exposure of embryos to complex PAH mixtures typical of weathered crude oil. We tested a series of model PAH compounds in zebrafish and found that individual 3-ring PAHs most abundant in crude oil are capable of inducing the syndrome, the primary etiology of which appears to be direct effects on cardiac function. PAH-induced cardiac dysfunction was associated with secondary consequences for late stages of cardiac morphogenesis, kidney development, neural tube structure, and the craniofacial skeleton. The impact of PAHs on the link between cardiac function and morphogenesis may contribute to the sublethal effects observed in wild fish species following oil spills. Overall, this experimental approach is an example of the emerging discipline of conservation medicine, or the application of biomedical research techniques to current problems in marine and freshwater conservation biology.
Biography:
B.S. Biology, Indiana University, 1988; Honors thesis in laboratory of Beth Raff
Ph.D. Genetics, Case Western Reserve University, 1995; laboratory of Terry Rosenberry (Department of Pharmacology)
M.D. Case Western Reserve University, 1996
Medical Teratology Fellow/Post-doc, University of Washington 1996-2001; Departments of Pediatrics and Biological Structure, laboratory of Henk Roelink.
In the Pacific Northwest many marine and anadromous fish species utilize habitat for spawning or rearing adjacent to areas with intense human land use activities. Consequently, early life history stages (embryos and larvae) are potentially exposed to a vast array of chemical contaminants from urban and agricultural sources. We are utilizing zebrafish to begin to understand the impacts of common aquatic contaminants (e.g. pesticides, herbicides, metals, petroleum hydrocarbons) on fish development. Mechanistic insight gained from these studies will be translated into technologies for assessing thresholds of toxicity in local species of concern that are otherwise difficult to study in the lab (e.g. salmonids). These studies are aimed to address data gaps concerning the effects of anthropogenic contaminants on fish populations that are trust resources for NOAA Fisheries.
We focused initial studies on petroleum-derived polycyclic aromatic hydrocarbons (PAHs), ubiquitous contaminants associated with urbanization of the Puget Sound basin. Studies prompted by the Exxon Valdez oil spill in Prince William Sound, which contaminated spawning grounds for Pacific herring and pink salmon, identified a syndrome of edema, spinal curvature and craniofacial defects induced by exposure of embryos to complex PAH mixtures typical of weathered crude oil. We tested a series of model PAH compounds in zebrafish and found that individual 3-ring PAHs most abundant in crude oil are capable of inducing the syndrome, the primary etiology of which appears to be direct effects on cardiac function. PAH-induced cardiac dysfunction was associated with secondary consequences for late stages of cardiac morphogenesis, kidney development, neural tube structure, and the craniofacial skeleton. The impact of PAHs on the link between cardiac function and morphogenesis may contribute to the sublethal effects observed in wild fish species following oil spills. Overall, this experimental approach is an example of the emerging discipline of conservation medicine, or the application of biomedical research techniques to current problems in marine and freshwater conservation biology.
Biography:
B.S. Biology, Indiana University, 1988; Honors thesis in laboratory of Beth Raff
Ph.D. Genetics, Case Western Reserve University, 1995; laboratory of Terry Rosenberry (Department of Pharmacology)
M.D. Case Western Reserve University, 1996
Medical Teratology Fellow/Post-doc, University of Washington 1996-2001; Departments of Pediatrics and Biological Structure, laboratory of Henk Roelink.
Non-Zebrafish Publications
Incardona JP. (2005) From sensing cellular sterols to assembling sensory structures. Developmental Cell 8: 798-799Incardona JP. (2003) Cellular cholesterol, membrane signaling, and disease. In Advances in Cell Aging and Gerontology, Vol 12. Ed. Mattson MP. Elsevier, London.
Incardona JP, Gruenberg J and Roelink H. (2002) Sonic hedgehog induces segregation of Patched and Smoothened in late endosomes. Current Biology 12: 983-995
Incardona JP, Lee JH, Robertson CP, Enga K, Kapur RP, and Roelink H. (2000) Receptor-mediated endocytosis of soluble and membrane-tethered forms of Sonic hedgehog by Patched-1. Proceedings of the National Academy of Sciences U.S.A. 97: 12044-12049
Incardona JP and Eaton S. (2000) Cholesterol in signal transduction. Current Opinion in Cell Biology 12: 193-203
Incardona JP and Roelink H. (2000) The role of cholesterol in Sonic hedgehog signaling and teratogen-induced holoprosencephaly. Cellular and Molecular Life Sciences 57(12):1709-1719
Incardona JP, Gaffield W, Lange Y, Cooney A, Pentchev PG, Liu S, Watson JA, Kapur RP and Roelink H. (2000) Cyclopamine inhibition of Sonic hedgehog signal transduction is not mediated through effects on cholesterol transport. Developmental Biology 224: 440–452
Neufeld E B, Wastney M, Patel S, Suresh S, Cooney AM, Dwyer NK, Roff CF, Ohno K, Morris JA, Carstea ED, Incardona JP, Strauss JF III, Vanier MT, Patterson MC, Brady RO, Pentchev PG and Blanchette-Mackie EJ, (1999) The Niemann-Pick C1 protein resides in a vesicular compartment linked to retrograde transport of multiple lysosomal cargo. Journal of Biological Chemistry 274:9627-9635
Incardona JP, Gaffield W, Kapur RP, and Roelink H. (1998) The teratogenic Veratrum alkaloid cyclopamine inhibits Sonic Hedgehog signal transduction. Development 125:3553-3562
Incardona JP and Rosenberry TL. (1996) Replacement of the glycoinositol phospholipid anchor of Drosophila acetylcholinesterase with a transmembrane domain does not alter sorting in neurons and epithelia but results in behavioral defects. Molecular Biology of the Cell 7:613-630
Incardona JP and Rosenberry TL. (1996) Construction and characterization of secreted and transmembrane-anchored forms of Drosophila acetylcholinesterase. A large truncation of the C-terminal signal peptide does not eliminate glycoinositol phospholipid anchoring. Molecular Biology of the Cell 7:595-611
Kimble M, Incardona JP, and Raff EC. (1989) A variant ß-tubulin isoform of Drosophila melanogaster (ß3) is expressed primarily in tissues of mesodermal origin in embryos and pupae, and is utilized in populations of transient microtubules. Developmental Biology 131:415-429