ZFIN ID: ZDB-PERS-030707-2
Incardona, John P.
Email: john.incardona@noaa.gov
URL: http://www.nwfsc.noaa.gov/research/staff/display_staffprofile.cfm?staffid=697
Affiliation: Conservation Medicine Group
Address: Ecotoxicology and Environmental Fish Health Program Environmental Conservation Division National Oceanic and Atmospheric Administration Northwest Fisheries Science Center 2725 Montlake Blvd E Seattle, WA 98112 USA
Country: United States
Phone: (206) 860-3347 or (206) 860-3411
Fax: (206) 860-3335
ORCID ID:


BIOGRAPHY AND RESEARCH INTERESTS
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.


PUBLICATIONS
Gardner, L.D., Peck, K.A., Goetz, G.W., Linbo, T.L., Cameron, J., Scholz, N.L., Block, B.A., Incardona, J.P. (2019) Cardiac remodeling in response to embryonic crude oil exposure involves unconventional NKX family members and innate immunity genes. The Journal of experimental biology. 222(Pt 21):
Incardona, J.P., Scholz, N.L. (2016) The influence of heart developmental anatomy on cardiotoxicity-based adverse outcome pathways in fish. Aquatic toxicology (Amsterdam, Netherlands). 177:515-525
McIntyre, J., Edmunds, R., Redig, M., Mudrock, E., Davis, J., Incardona, J.P., Stark, J.D., Scholz, N. (2016) Confirmation of stormwater bioretention treatment effectiveness using molecular indicators of cardiovascular toxicity in developing fish. Environmental science & technology. 50(3):1561-9
McIntyre, J., Edmunds, R., Anulacion, B., Davis, J., Incardona, J.P., Stark, J.D., Scholz, N. (2016) Severe coal tar sealcoat runoff toxicity to fish is prevented by bioretention filtration. Environmental science & technology. 50(3):1570-8
Edmunds, R.C., Gill, J.A., Baldwin, D.H., Linbo, T.L., French, B.L., Brown, T.L., Esbaugh, A.J., Mager, E.M., Stieglitz, J., Hoenig, R., Benetti, D., Grosell, M., Scholz, N.L., Incardona, J.P. (2015) Corresponding morphological and molecular indicators of crude oil toxicity to the developing hearts of mahi mahi. Scientific Reports. 5:17326
West, J.E., O'Neill, S.M., Ylitalo, G.M., Incardona, J.P., Doty, D.C., Dutch, M.E. (2014) An evaluation of background levels and sources of polycyclic aromatic hydrocarbons in naturally spawned embryos of Pacific herring (Clupea pallasii) from Puget Sound, Washington, USA. The Science of the total environment. 499C:114-124
Incardona, J.P., Swarts, T.L., Edmunds, R.C., Linbo, T.L., Aquilina-Beck, A., Sloan, C.A., Gardner, L.D., Block, B.A., and Scholz, N.L. (2013) Exxon Valdez to Deepwater Horizon: Comparable toxicity of both crude oils to fish early life stages. Aquatic toxicology (Amsterdam, Netherlands). 142-143:303-316
Jung, J.H., Hicken, C.E., Boyd, D., Anulacion, B.F., Carls, M.G., Shim, W.J., and Incardona, J.P. (2013) Geologically distinct crude oils cause a common cardiotoxicity syndrome in developing zebrafish. Chemosphere. 91(8):1146-55
Incardona, J.P., Linbo, T.L., and Scholz, N.L. (2011) Cardiac toxicity of 5-ring polycyclic aromatic hydrocarbons is differentially dependent on the aryl hydrocarbon receptor 2 isoform during zebrafish development. Toxicology and applied pharmacology. 257(2):242-9
Hicken, C.E., Linbo, T.L., Baldwin, D.H., Willis, M.L., Myers, M.S., Holland, L., Larsen, M., Stekoll, M.S., Rice, S.D., Collier, T.K., Scholz, N.L., and Incardona, J.P. (2011) Sublethal exposure to crude oil during embryonic development alters cardiac morphology and reduces aerobic capacity in adult fish. Proceedings of the National Academy of Sciences of the United States of America. 108(17):7086-7090
Scott, J.A., Incardona, J.P., Pelkki, K., Shepardson, S., and Hodson, P.V. (2011) AhR2-mediated, CYP1A-independent cardiovascular toxicity in zebrafish (Danio rerio) embryos exposed to retene. Aquatic toxicology (Amsterdam, Netherlands). 101(1):165-174
Hatlen, K., Sloan, C.A., Burrows, D.G., Collier, T.K., Scholz, N.L., and Incardona, J.P. (2010) Natural sunlight and residual fuel oils are an acutely lethal combination for fish embryos. Aquatic toxicology (Amsterdam, Netherlands). 99(1):56-64
Incardona, J.P., Carls, M.G., Day, H.L., Sloan, C.A., Bolton, J.L., Collier, T.K., and Scholz, N.L. (2009) Cardiac arrhythmia is the primary response of embryonic Pacific herring (Clupea pallasi) exposed to crude oil during weathering. Environmental science & technology. 43(1):201-207
Carvan III, M.J., Incardona, J.P., and Rise, M.L. (2008) Meeting the Challenges of Aquatic Vertebrate Ecotoxicology. Bioscience. 58(11):1015-1025
Carls, M.G., Holland, L., Larsen, M., Collier, T.K., Scholz, N.L., and Incardona, J.P. (2008) Fish embryos are damaged by dissolved PAHs, not oil particles. Aquatic toxicology (Amsterdam, Netherlands). 88(2):121-127
Lema, S.C., Schultz, I.R., Scholz, N.L., Incardona, J.P., and Swanson, P. (2007) Neural defects and cardiac arrhythmia in fish larvae following embryonic exposure to 2,2',4,4'-tetrabromodiphenyl ether (PBDE 47). Aquatic toxicology (Amsterdam, Netherlands). 82(4):296-307
Incardona, J.P., Day, H.L., Collier, T.K., and Scholz, N.L. (2006) Developmental toxicity of 4-ring polycyclic aromatic hydrocarbons in zebrafish is differentially dependent on AH receptor isoforms and hepatic cytochrome P4501A metabolism. Toxicology and applied pharmacology. 217(3):308-321
Stehr, C.M., Linbo, T.L., Incardona, J.P., and Scholz, N.L. (2006) The Developmental Neurotoxicity of Fipronil: Notochord Degeneration and Locomotor Defects in Zebrafish Embryos and Larvae. Toxicological sciences : an official journal of the Society of Toxicology. 92(1):270-278
Linbo, T.L., Stehr, C.M., Incardona, J.P., and Scholz, N.L. (2006) Dissolved copper triggers cell death in the peripheral mechanosensory system of larval fish. Environmental toxicology and chemistry. 25(2):597-603
Incardona, J.P., Carls, M.G., Teraoka, H., Sloan, C.A., Collier, T.K., and Scholz, N.L. (2005) Aryl Hydrocarbon Receptor-Independent Toxicity of Weathered Crude Oil during Fish Development. Environmental health perspectives. 113(12):1755-1762
Incardona, J.P., Collier, T.K., and Scholz, N.L. (2004) Defects in cardiac function precede morphological abnormalities in fish embryos exposed to polycyclic aromatic hydrocarbons. Toxicology and applied pharmacology. 196(2):191-205

NON-ZEBRAFISH PUBLICATIONS
Incardona JP. (2005) From sensing cellular sterols to assembling sensory structures. Developmental Cell 8: 798-799

Incardona 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