Developmental Biology

The Bohnsack Laboratory focuses on cranial neural crest biology in the context of the development of the anterior segment of the eye. We are specifically interested in the genetics and molecular pathways that underlie congenital eye disease pathogenesis. We utilize both in vivo (zebrafish) and in vitro (human embryonic stem cells) systems to model various eye diseases. We take advantage of the accessibility of zebrafish embryos to study in real-time the molecular regulation of the ocular neural crest, a transient population of stem cells that gives rise to portions of the cornea, iris, and aqueous humor drainage system in the anterior segment of the eye. In addition, we use human embryonic stem cells, which harbor known congenital eye disease-causing mutations, as a model that mirrors the human condition, yet is genetically accessible. These programs are improving our understanding of the genetic regulation of eye development and the pathophysiology of these blinding diseases which is importantly laying the groundwork for molecularly targeted treatments that aim to prevent blindness and restore vision in affected children.

Our interests lie in understanding mechanisms in kidney development, what leads to congenital anomalies of the kidney, and how chronic kidney disease develop in infants and children. We focus on the molecular signaling in kidney development to understand how disrupted processes lead to abnormal tissue development and renal anomalies. Current research projects study kidney progenitor cell populations and their differentiation to distinct renal cells that comprise the normal kidney. We strive to understand regulation of renal stem cells with the goal to contribute applied knowledge to the global effort of devising regenerative alternatives to kidney transplantation and dialysis.

Researchers at Stanley Manne Children’s Research Institute’s Kaushal Laboratory are leading studies in the use of cardiac mesenchymal stem cells (MSCs) to address cardiac stem cell therapies for heart failure. Their basic science research includes, among others, studies of: intravenous administration of neonatal mesenchymal stem cells (nMSCs) and its effect on functional recovery in a renal ischemia-reperfusion injury rodent model; nMSCs and cardiac functional recovery in a porcine model of acute myocardial infarction; and GDF-15’s function in preserving MSC-mediated right ventricular function in a porcine pressure-overload model.

These bench research studies, among others, form the basis for potential clinical trials using cardiac stem cells to address heart failure secondary to dilated cardiomyopathy, heart failure due to cardiomyopathy secondary to single ventricle anatomy or following myocardial infarction, and using cardiac mesenchymal stem cells to ameliorate the deleterious effects of cardiopulmonary bypass by decreasing post-bypass inflammatory response and improving left ventricular function.