Areas of Interest
Retina regeneration • Optic nerve regeneration • Neuromuscular regeneration • Activity-dependent control of muscle gene expression
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 Müller 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 Müller glia reprogramming in the injured zebrafish retina. This information then informs us on strategies for stimulating Müller 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.
Honors & Awards
1994 University of Michigan Scientist Award
1995 Mental Health Research Institute Discovery Award
2003 Research Scientist Achievement Award of the Office of the VP for Research
Leptin and IL-6 Family Cytokines Synergize to Stimulate Müller Glia Reprogramming and Retina Regeneration Zhao, X-F., Wan, J., Powell, C., Ramachandran, R., Myers Jr., M.G., Goldman, D.
Cell Reports 2014 Available on line Sept 25 [Epub ahead of print]
Retinal Injury, Growth Factors, and Cytokines Converge on β-Catenin and pStat3 Signaling to Stimulate Retina Regeneration Jin Wan, J., Zhao, X-F., Vojtek, J. and Goldman, D. Cell Reports 2014 Available on line Sept 25 [Epub ahead of print]
Zinc-Binding Domain-Dependent, Deaminase-Independent Actions of Apolipoprotein B mRNA Editing Enzyme, Catalytic Polypeptide 2 (Apobec2) Mediate Its Effect on Zebrafish Retina Regeneration.
Powell, C., Cornblath, E. and Goldman, D.
J Biol Chem 2014; Sep 4. pii: jbc.M114.603043. [Epub ahead of print]
Excitotoxic brain injury in adult zebrafish stimulates neurogenesis and long-distance neuronal integration. Skaggs, K., Goldman, D. and Parent, J.M. Glia 2014; Jul 15. doi: 10.1002/glia.22726. [Epub ahead of print]
Regeneration, morphogenesis and self-organization. Goldman, D. Development 2014; 141:2745-2749.
Müller glial cell reprogramming and retina regeneration. Goldman, D. Nat Rev Neurosci 2014; 15:431-442.
mTORC1 promotes denervation-induced muscle atrophy through a mechanism involving the activation of FoxO and E3 ubiquitin ligases. Tang, H., Inoki, K., Lee, M., Wright, E., Khuon, A., Khuon, A., Sugiarto, S., Garner, M., Paik, J., Depinho, R., Goldman, D., Guan, K-L., and Shrager, J.B. Science Signaling 2014; 7:ra18.
Jak/Stat signaling stimulates zebrafish optic nerve regeneration and overcomes the inhibitory actions of Socs3 and Sfpq. Elsaeidi. F., Bemben, M.A., Zhao X-F. and Goldman D. J Neurosci 2014; 34:2632-2644.
Analysis of DNA methylation reveals a partial reprogramming of the Müller glia genome during retina regeneration. Powell, C., Grant, A. R., Cornblath, E. and Goldman, D. Proc Natl Acad Sci USA 2013; 110:19814-19819.
Insm1a-mediated gene repression is essential for the formation and differentiation of Müller 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 Müller glia dedifferentiation and retina regeneration.
Wan, J., Ramachandran, R. and Goldman, D. Dev Cell 2012; 22:334-347.
Injury-dependent Müller 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.
Ascl1a/Dkk/beta-catenin signaling pathway is necessary and glycogen synthase kinase-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.