Current Research Interests:
Blinding eye diseases like macular degeneration and glaucoma are among the top 10 disabilities affecting people. A major goal of neuroscientists is to identify strategies for restoring lost sight to those suffering from blindness. One approach is to use endogenous repair pathways to regenerate damaged retinal tissue. Unlike mammals, fish are able to regenerate an injured retina and this regeneration leads to restoration of lost sight. Our lab has discovered that Muller glia residing in the zebrafish retina respond to retinal injury and disease by dedifferentiating into a multipotent retinal stem cell that is able to regenerate all retinal cell types. Our research focuses on unraveling the cellular, molecular and biochemical mechanisms that drive and allow Muller glia reprogramming in the injured zebrafish retina. This information then informs us on strategies for stimulating Muller glia dedifferentiation and retina regeneration in mammals.
Muscular dystrophies are a group of diseases that are characterized by progressive muscle weakness and degeneration of skeletal muscle. These diseases are often associated with muscle atrophy and inefficient neuromuscular communication. Similarly, motor neuron diseases like ALS result in abrogation of neuromuscular communication leading to muscle atrophy and weakness. Our lab is interested in identifying interventions that will help restore neuromuscular communication and muscle function in people afflicted with muscular dystrophies and motor neuron diseases. We aim to identify signaling mechanisms by which muscle activity controls the expression of genes that regulate neuromuscular junction regeneration and muscle function in adult animals. It is our hope that this information may suggest novel strategies for restoring neuromuscular communication and muscle function in those suffering from muscular dystrophies and motor neuron diseases. Similar to our studies of retina regeneration, we rely on the tools of cell biology, molecular biology and biochemistry to unravel the mechanisms underlying neuromuscular communication and regeneration.
KLF-dependent optic axon regeneration
Injury-dependent Muller glia dedifferentiation
Retina Regeneration - An animation designed and produced by Daniel Goldman and Harvey Goldman.
Click on the image to play.
Activity-dependent neuromuscular regeneration
Insm1a-mediated gene repression is essential for the formation and
differentiation of Muller-glia-derived progenitors in the injured retina.
Ramachandran, R., Zhao, X-F. and Goldman, D.
Nature Cell Biology, 2012;14:1013-1023.
HB-EGF is necessary and sufficient for Muller glia dedifferentiation and retina regeneration.
Wan, J., Ramachandran, R. and Goldman, D.
Dev Cell, 2012; 22:334-347.
Injury-dependent Muller glia and ganglion cell reprogramming during tissue regeneration requires Apobec2a and Apobec2b.
Powell, C., Elsaeidi, F. and Goldman, D.
J Neurosci, 2012; 32:1096-1109.
An Ascl1a/Dkk/beta-Catenin signaling pathway is necessary and GSK-3beta inhibition is sufficient for zebrafish retina regeneration.
Ramachandran, R., Zhao, X-F. and Goldman, D.
Proc Natl Acad Sci USA, 2011; 108:15858-15863.
Deletion of a remote enhancer near ATOH7 disrupts retinal neurogenesis, causing NCRNA disease.
Ghiasvand, N., Rudolph, D., Mashayekhi, M., Brzezinski, J., Goldman, D. and Glaser, T.
Nature Neurosci, 2011; 14:578-586.
Myogenin regulates denervation-dependent muscle atrophy in mouse soleus muscle.
Macpherson, P. C. D., Wang, X. and Goldman, D.
J. Cell. Biochem, 2011; 112:2149-2159.
Ascl1a regulates Müller glia dedifferentiation and retinal regeneration through a Lin-28-dependent, let-7 microRNA signalling pathway.
Ramachandran R, Fausett BV, Goldman D.
Nature Cell Biol, 2010; 12:1101-1107.
Conditional gene expression and lineage tracing of tuba1a expressing cells during zebrafish development and retina regeneration
Ramachandran R, Reifler A, Parent J, Goldman D.
J Comp Neurol, 2010; 518:4196-4212.
Tuba1a gene expression is regulated by KLF6/7 and is necessary for CNS development and regeneration in zebrafish.
Veldman MB, Bemben MA, Goldman D.
Mol Cell Neurosci 2010; 43:370-383.
A histone deacetylase 4/myogenin positive feedback loop coordinates denervation-dependent gene induction and suppression.
Tang H, Macpherson P, Marvin M, Meadows E, Klein WH, Yang XJ, Goldman D.
Mol Biol Cell, 2009; 20:1120-1131.
The proneural basic helix-loop-helix gene ascl1a is required for retina regeneration.
Fausett BV, Gumerson JD, Goldman D.
J Neurosci, 2008; 28:1109-1117.
Gene expression analysis of zebrafish retinal ganglion cells during optic nerve regeneration identifies KLF6a and KLF7a as important regulators of axon regeneration.
Veldman MB, Bemben MA, Thompson RC, Goldman D.
Dev Biol, 2007; 312:596-612.
Activity-dependent gene regulation in skeletal muscle is mediated by a histone deacetylase (HDAC)-Dach2-myogenin signal transduction cascade.
Tang H, Goldman D.
Proc Natl Acad Sci U S A, 2006; 103:16977-16982.
A reporter-assisted mutagenesis screen using alpha 1-tubulin-GFP transgenic zebrafish uncovers missteps during neuronal development and axonogenesis.
Gulati-Leekha A, Goldman D.
Dev Biol, 2006; 296:29-47.
A role for alpha1 tubulin-expressing Müller glia in regeneration of the injured zebrafish retina.
Fausett BV, Goldman D.
J Neurosci, 2006; 26:6303-6313.