Using the zebrafish model for chemical fishing expeditions, we examine conserved regulators of stem cell specification and growth, ultimately striving towards clinical therapies to alleviate human hematopoietic and hepatic disease.
to explore endodermal progenitor cell specification, organ differentiation, and growth.
Our laboratory seeks to understand the signals that indicate organ injury and regulate growth and regeneration. The inability to recover from acute injury can lead to organ failure, while a dysregulated regenerative response in the setting of chronic injury may contribute to cancer formation. Our specific interest is to define the similarities between development and regeneration of the liver, an important organ for the organism’s metabolism and protein synthesis with remarkable regenerative capacities. We investigate zebrafish as the primary model to discover novel regulatory pathways of liver development and evaluate their importance for recovery after toxic and physical injury. Using chemical and genetic modulation, we assess organ formation, repair and carcinogenesis by in vivo imaging, functional genomic methods, and histological analysis to define the principal molecular and cellular mechanisms essential for organ growth.
Hematopoietic stem cells (HSCs) give rise to each of the blood lineages found in the adult vertebrate; the gene programs regulating HSC development and homeostasis are highly evolutionarily conserved. Dysregulated hematopoiesis can result in a variety of hematologic malignancies, including leukemia. We use chemical biology and genetic methods in zebrafish to identify and integrate pathways regulating hematopoietic niche formation, stem cell induction, and HSC function. To investigate the conservation of regulatory effects and translational applications, we utilize murine HSC production and regeneration assays as well as human umbilical cord blood xenograft models. Our current work examines the following topics in the field of hematopoietic stem cell biology: a) the characterization of novel transcriptional regulators of hematopoietic induction; b) the biological rationale for the shifting sites of hematopoietic production in the vertebrate embryo; c) the impact of environmental factors on HSC production and leukemogenesis.