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The Kullman laboratory employs molecular, comparative, and functional genomic approaches to investigate how environmental stressors dysregulate metabolic networks that govern critical steps of cell differentiation and embryonic development. Our research focuses on nuclear receptors and ligand-activated transcription factors, which coordinate complex cellular responses to endogenous and exogenous signals. Nuclear receptors play well-established roles in vertebrate development, and perturbations in their signaling can produce profound effects during embryogenesis or manifest later in life, providing a mechanistic basis for the developmental origins of adult disease. A central aim of our work is to understand how alterations in signaling pathways, metabolic networks, and epigenetic regulation guide stem cell lineage commitment. Emerging evidence suggests that extrinsic factors, including diet and environmental exposures, can disrupt these networks and influence cell fate decisions. We are applying this paradigm to study the impact of nutritional and environmental factors on developmental and degenerative diseases. For in vivo studies, we use zebrafish (Danio rerio) and medaka (Oryzias latipes), vertebrate models that are increasingly employed to study human health and disease due to their genetic tractability, transparency, and suitability for forward and reverse genetic approaches. Our research leverages the assumption that evolutionarily conserved regulatory processes underlie observed pathologies, allowing us to identify metabolic pathways of relevance to disease etiology.
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