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    By Alpha|By Interest|Emeritus


Daniel Goldman, Ph. D.
Research Professor, MBNI
Professor, Department of Biological Chemistry

5045 BSRB
109 Zina Pitcher PL
Ann Arbor , MI 48109-2200

neuroman@umich.edu

734-936-2057

 

Current Research Interests:

Sight is our most precious sense. Diseases of the retina, like macular degeneration and glaucoma cause blindness and are among the top 10 disabilities affecting people.  Macular degeneration results in death of photoreceptors, while glaucoma results in optic nerve degeneration and death of retinal ganglion cells. Although there are a number of approaches to restoring sight to people suffering from these diseases, we think a regenerative approach would be best. Unfortunately, mammals do not normally regenerate retinal neurons or optic axons. However, hope comes from the observation that teleost fish, like zebrafish, have remarkable regenerative abilities and can regenerate a damaged retina and optic nerve. Because the zebrafish and mammalian retina share structure and function, we suspect that mechanisms driving retina and optic nerve regeneration in zebrafish will suggest regenerative strategies that can be applied to mammals. 

In the retina of fish and mammals there is only one major glial cell type referred to as a Muller glia. Muller glial cells are traditionally thought to participate in retina structure and homeostasis. We found that in zebrafish, Muller glia respond to retinal injury by undergoing a reprogramming event that endows them with properties of a retinal stem cell. These reprogrammed Muller glia divide to produce a progenitor that amplifies and is capable of regenerating all major retinal neuron types. Using a variety of molecular, genetic, biochemical and cell biological approaches, we have identified and characterized many of the signaling pathways and gene expression programs that underlie Muller glial cell reprogramming and retina regeneration. Similar approaches have been used to study optic nerve regeneration. This information is being used to suggest strategies for stimulating retina and optic nerve regeneration in mammals.

 



KLF-dependent optic axon regeneration


Injury-dependent Muller glia dedifferentiation


Retina Regeneration

Retina Regeneration - An animation designed and produced by Daniel Goldman and Harvey Goldman.

Click on the image to play.



Honors and Awards
1994  University of Michigan, Research Scientist Recognition Award
1995  Mental Health Research Institute Discovery Award
2001  Wilson Scholar, Wilson Medical Research Foundation
2003  University of Michigan, Research Scientist Achievement Award
2010  Undergraduate Research Opportunity Program Recognition Award for Outstanding Research Mentorship
2013  Research to Prevent Blindness Innovative Ophthalmic Research Award
2014  Bernard W. Agranoff Collegiate Professor of Neuroscience, University of Michigan
2014  Elected AAAS Fellow, American Association for the Advancement of Science


Selected Publications:

Zebrafish Muller glia-derived progenitors are multipotent, exhibit proliferative biases and regenerate excess neurons.
Powell, C. Cornblath, E., Elsaeidi, F., Wan, J. and Goldman, D. Scientific Reports 2016; 6:24851.

Retina regeneration in zebrafish.
Wan, J. and Goldman, D. Current Opinion Genetics and Development 2016; 40:41-47.

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; 289:28924-28941.

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.

 

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