ROBERT LIPINSKI, PHD

Assistant Professor in Comparative Biosciences

rjlipinski@wisc.edu

3254 Veterinary Medicine Building

Research Interests:Toxicology, embryology, teratology, small animal imaging, Hedgehog signaling, cleft lip and palate, fetal alcohol syndrome, holoprosencephaly

Research

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.

Link To Lab

Publications
  • Galen W. Heyne, Joshua L. Everson, Lydia J. Ansen-Wilson, Cal G. Melberg, Dustin M. Fink, Kia F. Parins, Padydeh Doroodchi, Caden M. Ulschmid, Robert J. Lipinski. Gli2 gene dosage and gene-environment interaction illuminate the etiological complexity of holoprosencephaly. Disease Models & Mechanisms 2016 : doi: 10.1242/dmm.026328
  • Lipinski, R.J., H.T. Holloway, S.K. O’Leary-Moore, J.J. Ament, S.J. Pecevich, G.P. Cofer, F. Budin, J.L. Everson, G.A. Johnson, and K.K. Sulik, (2014). Characterization of subtle brain abnormalities in a mouse model of Hedgehog pathway antagonist-induced cleft lip and palate. PLOS ONE.  21;9(7):e
  • Kietzman H.W., J.E. Everson, K.K. Sulik, and R.J. Lipinski (2014).  The teratogenic effects of prenatal ethanol exposure are exacerbated by Sonic Hedgehog or Gli2 haploinsufficiency in the mouse.  PLOS ONE.  9(2):e89448.  Epub 2014 Feb 19.
  • 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, 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.
Mentor to METC Graduate Students:
  • Josh Everson (Current);
  • Hannah Chung (Current)