Ava Udvadia

Education

• Postdoctoral Fellow, Neuroscience, Duke University, 1996-2001
• PhD, Molecular Cancer Biology, Duke University, 1995
• BS, Cell and Molecular Biology, University of Michigan, 1989

Research Interests

\nThe broad focus of the Udvadia lab is on cellular programming that governs nervous system development and regeneration. More specifically, we use fish and rodent models to understand how dynamic changes in transcription factor activity, chromatin accessibility and chromatin architecture govern:

1. Reprogramming of adult retinal ganglion cell neurons for successful CNS optic nerve regeneration. In humans, optic nerve damage caused by trauma or optic neuropathies such as glaucoma can result in permanent visual loss. The permanence of the damage is due to a failure of the human central nervous system (CNS) to support regenerative nerve growth. In contrast, fish naturally respond to optic nerve injury by re-establishing the growth capacity of CNS neurons and eventually recovering visual function. It is well known that the cellular programming regulating nerve growth and guidance in the developing visual system is highly conserved between fish and humans. Once the mature visual circuitry has been established, the cells undergo a change in cellular programming from a growth state to one that enables neurotransmission. Thus, what appears to set fish apart from humans is their ability to reprogram adult retinal neurons for wiring in response to optic nerve injury. We hypothesize that discrete evolutionary changes in regeneration-associated gene regulatory interactions in mammals disrupt an otherwise evolutionarily conserved program for functional regeneration of RGC axons. Our current research in this area focuses on: (1) Changes in 3D chromatin architecture that enable regenerative reprogramming, and (2) Dynamic changes in transcription factor interactions that drive stage-specific regeneration-associated gene expression. The long-term goal of this part of our research program is to elucidate key regulatory interactions missing in the mammalian response to optic nerve injury when compared to that of zebrafish in order to discover therapeutic approaches for promoting functional optic nerve regeneration in humans that can restore visual function.

2. Programming decisions for ectodermal and mesoectodermal cell fate choices during cranial neural crest cell differentiation. Disruption of cranial neural crest (CNC) cell development can manifest as a wide variety of human congenital birth defects, including malformations of the craniofacial skeleton, and can also lead to the formation of aggressive tumors, such as neuroblastoma. Contributing to the diversity of anomalies is the ability of the CNC to give rise to both ectodermal cell types, such as sensory ganglia and peripheral glia, and mesectodermal cell types, including the cartilage, bone, and connective tissues of the face. Underlying this remarkable potential is a temporal cascade of events that regulate CNC development from specification to migration and, finally, lineage diversification - a multistep process where CNC progenitors progressively acquire characteristics necessary for cell type-specific function. Our current research in this area is focused on: (1) elucidating the temporally-regulated gene regulatory modules governing CNC differentiation, and (2) investigating the role of Cabin1, a regulator of transcription factors in the MEF2 and NFAT family, in regulating CNC differentiation. The long-term goal of this part of our research program is to discover molecular targets of genetic and environmental factors that lead to CNC-related malformations, and developing potential therapeutic treatments.