Robert J Lipinski
Department of Comparative Biosciences
- B.S. in Biology, University of Wisconsin-Madison, 2002
- Ph.D. in Molecular and Environmental Toxicology, University of Wisconsin-Madison, 2008
- Post-doctoral research in embryology and teratology, University of North Carolina at Chapel Hill, 2009-2013
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Perturbation of the signaling pathways that guide development of the brain and face can cause serious craniofacial birth defects. The focus of our laboratory’s research is to identify genetic and environmental factors that disrupt development of the brain and face, and examine their potential interaction in the genesis of etiologically-complex birth defects.
Currently, our research efforts are focused on clefts of the lip and palate, which are the most common human craniofacial birth defect. Prevention strategies for cleft lip and palate have remained elusive because our current understanding of causative factors is inadequate. Addressing the multifactorial basis of these birth defects, we pursue a multidisciplinary approach based in the complementary disciplines of toxicology, cellular signaling, embryology, and genetics, while integrating traditionally disparate conceptual and experimental approaches.
We have demonstrated in the mouse that temporally-specific in utero exposure to the Hedgehog signaling antagonist, cyclopamine, causes cleft lip and palate, mimicking human clinical phenotypes. Currently, we are examining the role of Hedgehog signaling in brain and face development, and identifying the target genes which mediate the initial pathogenesis of cleft lip and palate. Using cell-based assays, we have also identified a battery of structurally diverse Hedgehog signaling antagonists with human exposure potential. Ongoing efforts are focused on further identification and teratogenic characterization of environmental agents that inhibit the Hedgehog signaling pathway, particularly in the context of genetic predisposition.
The long term goal of our research is to identify markers of high-risk populations and to develop ameliorative strategies based upon defined windows of exposure to culpable environmental agents, which could ultimately lead to the prevention of these common and morbid human birth defects.
VISIT THE LIPINSKI LAB WEBSITE
- Veterinary Developmental Anatomy
Lipinski, RJ, P Hammond, SK O’Leary-Moore, et al., (2012). Ethanol-induced face-brain dysmorphology patterns are correlative and exposure-stage dependent. PLoS ONE. 7(8):e43067. Epub 2012 Aug 22.
Lipinski, RJ, C Song, KK Sulik, et al., (2010). Cleft lip and palate results from Hedgehog signaling antagonism in the mouse: Phenotypic characterization and clinical implications. Birth Defects Res A Clin Mol Teratol. 88(4):232-40
Lipinski, RJ, EA Godin, SK O’Leary-Moore, SE Parnell, and KK Sulik (2010). Genesis of teratogen-induced holoprosencephaly in the mouse. Am. J. Med. Gen. C 154C(1):29-42.
Lipinski, RJ and W Bushman (2010). Identification of Hedgehog Signaling Inhibitors with Relevant Human Exposure by Small Molecule Screening. Toxicol. In vitro. 24(5):1404-9.
Lipinski, RJ, PR Hutson, PW Hannam, RJ, et al., (2008). Dose- and route-dependent teratogenicity, toxicity, and pharmacokinetic profiles of the Hedgehog signaling antagonist cyclopamine in the mouse. Toxicol. Sci. 104(1):189-97.