Affecting millions of newborns each year, birth defects profoundly impact individuals, families, and communities.  The focus of our research group is to better understand human birth defects, dissect their complex causes, and apply this knowledge to the development of prevention strategies. 

We are resolving the gene-environment puzzle to inform birth defect prevention strategies

Gene-environment interactions in birth defect etiology: challenges and opportunities.  Current Topics in Developmental Biology.

Gli2 gene-environment interactions contribute to the etiological complexity of holoprosencephaly: evidence from a mouse model.  Disease Models and Mechanisms.

Gene-environment interactions: aligning birth defects research with complex etiology. Development.

Identifying environmental risk factors and gene-environment interactions in holoprosencephaly.  Birth Defects Research

We are developing new models and identifying novel mechanisms of human birth defects 

Disruption of DNA methylation–mediated cranial neural crest proliferation and differentiation causes orofacial clefts in mice.  PNAS.

A microphysiological approach to evaluate effectors of intercellular Hedgehog signaling in development.  Frontiers in Cell and Developmental Biology.

Sonic Hedgehog Signaling in Cranial Neural Crest Cells Regulates Microvascular Morphogenesis in Facial Development. Frontiers in Cell and Developmental Biology.

Definition of critical periods for Hedgehog pathway antagonist-induced holoprosencephaly, cleft lip, and cleft palate. PLOS ONE.

We are identifying and characterizing environmental birth defect risk factors

Developmental toxicity assessment of piperonyl butoxide exposure targeting Sonic hedgehog signaling and forebrain and face morphogenesis in the mouse: an in vitro and in vivo study.  Environmental Health Perspectives.

Prenatal Exposure to Pesticides and Risk for Holoprosencephaly: A Case-Control Study.  Environmental Health.

Pharmacokinetic analysis of acute and dietary exposure to piperonyl butoxide in the mouse.  Toxicology Reports.

Ethanol-induced face-brain dysmorphology patterns are correlative and exposure-stage dependent. PLOS ONE.

We are identifying human disease genes and defining their function in development

Sonic Hedgehog regulation of Foxf2 promotes cranial neural crest mesenchyme proliferation and is disrupted in cleft lip morphogenesis. Development.

Cohesin complex-associated holoprosencephaly. Brain.

Genome-wide enrichment of de novo coding mutations in orofacial cleft trios. American Journal of Human Genetics.

Loss of Function Variants in PPP1R12A Cause Holoprosencephaly Spectrum and Urogenital Malformations. American Journal of Human Genetics.

Trio-based GWAS identifies novel associations and subtype-specific risk factors for cleft palate.  HGG Advances.

We are elucidating cellular signaling pathways that drive embryonic development

Identification of Sonic Hedgehog regulated genes and biological processes in the cranial neural crest mesenchyme by comparative transcriptomics. BMC Genomics.

Frem1 activity is regulated by Sonic hedgehog signaling in the cranial neural crest mesenchyme during midfacial morphogenesis.  Dev. Dynamics.

Coordinated D-Cyclin/Foxd1 activation drives mitogenic activity of Sonic Hedgehog signaling pathway.  Cellular Signalling.

Serotonin regulates calcium homeostasis in lactation by epigenetic activation of Hedgehog signaling. Mol. Endocrinol.