ZFIN ID: ZDB-LAB-090729-1
Mumm Lab
PI/Director: Mumm, Jeff
Co-PI / Senior
Zhang, Liyun
Contact Person: Mumm, Jeff
Email: jmumm3@jhmi.edu
URL: https://mummlab.wordpress.com/
Address: Johns Hopkins School of Medicine Wilmer Eye Institute Smith Bldg, 4001 400 N Broadway Baltimore, MD, 21287 USA
Country: United States
Phone: (410) 502-2210
Line Designation: jh

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Cellular Regeneration

To advance studies of cellular regeneration we developed an inducible cell-type specific ablation technique based on transgenic expression of the prodrug converting enzyme, nitroreductase. When applied in zebrafish, this technique opens up several potent avenues of investigation: 1) Cell-specific regeneration paradigms and associated degenerative disease models, 2) Neural function studies, linking neuronal cell subtypes to discrete behaviors and/or percepts, 3) Correlations between extent of neuronal injury/repair with the degree of functional loss/recovery, and 4) Large-scale genetic and chemical screens for systematically dissecting mechanisms that regulate the regeneration of individual cell types. Regarding the latter point, two recent initiatives are particularly exciting for us:

1) We have initiated unbiased ‘forward’ genetic screens to identify mutant zebrafish that are incapable of regenerating specific neuronal subtypes in the retina. Identifying the genes mutated will provide valuable insights into factors required for productive retinal repair. In addition, ‘regeneration-deficient’ mutants provide a resource for large-scale compound screens aimed at identifying drugs that stimulate regeneration.

2) We have recently developed a high-throughput screening system for quantifying cell loss and regeneration in living fish over time, termed Automated Reporter Quantification in vivo (ARQiv). A key advantage to ARQiv, as compared to other whole-organisms screening platforms, is the increase in throughput to true HTS-compatible levels (>50,000 fish per day). ARQiv is also highly versatile, being adaptable to a range of reporter assays and capable of screening zebrafish from embryonic to juvenile stages. The versatility and ease of deployment of this platform should serve to rapidly expand the kinds of whole-organism HTS assays for which the zebrafish system can be utilized, and thereby providing a simple solution to current “biological validation” bottlenecks plaguing drug discovery efforts.

Throughout our research, an emphasis is placed on translating what is learned in the zebrafish model system toward the development novel therapies for stimulating dormant regenerative capacities in humans.

Thierer, James (Jay) Post-Doc Ceisel, Anneliese Graduate Student Emmerich, Kevin Graduate Student
Montalvo, Omar Research Staff Saxena, Meera T. Research Staff

Mulligan, T.S., Mumm, J.S. (2024) Selective Cell Ablation Using an Improved Prodrug-Converting Nitroreductase. Methods in molecular biology (Clifton, N.J.). 2707:223234223-234
Emmerich, K., Walker, S.L., Wang, G., White, D.T., Ceisel, A., Wang, F., Teng, Y., Chunawala, Z., Graziano, G., Nimmagadda, S., Saxena, M.T., Qian, J., Mumm, J.S. (2023) Transcriptomic comparison of two selective retinal cell ablation paradigms in zebrafish reveals shared and cell-specific regenerative responses. PLoS Genetics. 19:e1010905e1010905
Tucker, T.R., Knitter, C.A., Khoury, D.M., Eshghi, S., Tran, S., Sharrock, A.V., Wiles, T.J., Ackerley, D.F., Mumm, J.S., Parsons, M.J. (2023) A new model of inducible chronic hyperglycemia. Disease models & mechanisms. 16(8):
Emmerich, K., White, D.T., Kambhampati, S.P., Casado, G.L., Fu, T.M., Chunawala, Z., Sahoo, A., Nimmagadda, S., Krishnan, N., Saxena, M.T., Walker, S.L., Betzig, E., Kannan, R.M., Mumm, J.S. (2023) Nanoparticle-based targeting of microglia improves the neural regeneration enhancing effects of immunosuppression in the zebrafish retina. Communications biology. 6:534534
Fogerty, J., Song, P., Boyd, P., Grabinski, S.E., Hoang, T., Reich, A., Cianciolo, L.T., Blackshaw, S., Mumm, J.S., Hyde, D.R., Perkins, B.D. (2022) Notch inhibition promotes regeneration and immunosuppression supports cone survival in a zebrafish model of inherited retinal dystrophy. The Journal of neuroscience : the official journal of the Society for Neuroscience. 42(26):5144-5158
Hall, C.J., Astin, J.W., Mumm, J.S., Ackerley, D.F. (2022) A New Transgenic Line for Rapid and Complete Neutrophil Ablation. Zebrafish. 19(3):109-113
Macklin, B.L., Lin, Y.Y., Emmerich, K., Wisniewski, E., Polster, B.M., Konstantopoulos, K., Mumm, J.S., Gerecht, S. (2022) Intrinsic epigenetic control of angiogenesis in induced pluripotent stem cell-derived endothelium regulates vascular regeneration. NPJ Regenerative medicine. 7:28
Jawahar, J., McCumber, A.W., Lickwar, C.R., Amoroso, C.R., de la Torre Canny, S.G., Wong, S., Morash, M., Thierer, J.H., Farber, S.A., Bohannan, B.J.M., Guillemin, K., Rawls, J.F. (2022) Starvation causes changes in the intestinal transcriptome and microbiome that are reversed upon refeeding. BMC Genomics. 23:225
Sharrock, A.V., Mulligan, T.S., Hall, K.R., Williams, E.M., White, D.T., Zhang, L., Emmerich, K., Matthews, F., Nimmagadda, S., Washington, S., Le, K.D., Meir-Levi, D., Cox, O.L., Saxena, M.T., Calof, A.L., Lopez-Burks, M.E., Lander, A.D., Ding, D., Ji, H., Ackerley, D.F., Mumm, J.S. (2022) NTR 2.0: a rationally engineered prodrug-converting enzyme with substantially enhanced efficacy for targeted cell ablation. Nature Methods. 19:205-215
Zhang, L., Chen, C., Fu, J., Lilley, B., Berlinicke, C., Hansen, B., Ding, D., Wang, G., Wang, T., Shou, D., Ye, Y., Mulligan, T., Emmerich, K., Saxena, M.T., Hall, K.R., Sharrock, A.V., Brandon, C., Park, H., Kam, T.I., Dawson, V.L., Dawson, T.M., Shim, J.S., Hanes, J., Ji, H., Liu, J.O., Qian, J., Ackerley, D.F., Rohrer, B., Zack, D.J., Mumm, J.S. (2021) Large-scale phenotypic drug screen identifies neuroprotectants in zebrafish and mouse models of retinitis pigmentosa. eLIFE. 10:
Ganzen, L., Ko, M.J., Zhang, M., Xie, R., Chen, Y., Zhang, L., James, R., Mumm, J., van Rijn, R.M., Zhong, W., Pang, C.P., Zhang, M., Tsujikawa, M., Leung, Y.F. (2021) Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa. Scientific Reports. 11:11432
Yuan, M., White, D., Resar, L., Bar, E., Groves, M., Cohen, A., Jackson, E., Bynum, J., Rubens, J., Mumm, J., Chen, L., Jiang, L., Raabe, E., Rodriguez, F., Eberhart, C.G. (2020) Conditional reprograming culture conditions facilitate growth of lower grade glioma models. Neuro-Oncology. 23(5):770-782
Asnaghi, L., White, D.T., Yoon, L., Price, A., Lee, G.Y., Sahoo, A., Mumm, J.S., Eberhart, C.G. (2019) Downregulation of Nodal inhibits metastatic progression in retinoblastoma. Acta neuropathologica communications. 7:137
White, D.T., Saxena, M.T., Mumm, J.S. (2019) Let's get small (and smaller): Combining zebrafish and nanomedicine to advance neuroregenerative therapeutics. Advanced drug delivery reviews. 148:344-359
Asnaghi, L., White, D.T., Key, N., Choi, J., Mahale, A., Alkatan, H., Edward, D.P., Elkhamary, S.M., Al-Mesfer, S., Maktabi, A., Hurtado, C.G., Lee, G.Y., Carcaboso, A.M., Mumm, J.S., Safieh, L.A., Eberhart, C.G. (2018) ACVR1C/SMAD2 signaling promotes invasion and growth in retinoblastoma. Oncogene. 38(12):2056-2075
Unal Eroglu, A., Mulligan, T.S., Zhang, L., White, D.T., Sengupta, S., Nie, C., Lu, N.Y., Qian, J., Xu, L., Pei, W., Burgess, S.M., Saxena, M.T., Mumm, J.S. (2018) Multiplexed CRISPR/Cas9 Targeting of Genes Implicated in Retinal Regeneration and Degeneration. Frontiers in cell and developmental biology. 6:88
White, D.T., Sengupta, S., Saxena, M.T., Xu, Q., Hanes, J., Ding, D., Ji, H., Mumm, J.S. (2017) Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina. Proceedings of the National Academy of Sciences of the United States of America. 114(18):E3719-E3728
White, D.T., Eroglu, A.U., Wang, G., Zhang, L., Sengupta, S., Ding, D., Rajpurohit, S.K., Walker, S.L., Ji, H., Qian, J., Mumm, J.S. (2016) ARQiv-HTS, a versatile whole-organism screening platform enabling in vivo drug discovery at high-throughput rates. Nature Protocols. 11:2432-2453
Fiskus, W., Coothankandaswamy, V., Chen, J., Ma, H., Ha, K., Saenz, D.T., Krieger, S.S., Mill, C.P., Sun, B., Huang, P., Mumm, J.S., Melnick, A., Bhalla, K.N. (2016) SIRT2 deacetylates and inhibits the peroxidase activity of peroxiredoxin-1 to sensitize breast cancer cells to oxidant stress inducing agents. Cancer research. 76(18):5467-78
Johnson, K., Barragan, J., Bashiruddin, S., Smith, C.J., Tyrrell, C., Parsons, M.J., Doris, R., Kucenas, S., Downes, G.B., Velez, C.M., Schneider, C., Sakai, C., Pathak, N., Anderson, K., Stein, R., Devoto, S.H., Mumm, J.S., Barresi, M.J. (2016) Gfap-positive radial glial cells are an essential progenitor population for later-born neurons and glia in the zebrafish spinal cord. Glia. 64(7):1170-89
Zhang, L., Xiang, L., Liu, Y., Venkatraman, P., Chong, L., Cho, J., Bonilla, S., Jin, Z.B., Pang, C.P., Ko, K.M., Ma, P., Zhang, M., Leung, Y.F. (2016) A Naturally-Derived Compound Schisandrin B Enhanced Light Sensation in the pde6c Zebrafish Model of Retinal Degeneration. PLoS One. 11:e0149663
Chan, X.Y., Black, R., Dickerman, K., Federico, J., Levesque, M., Mumm, J., Gerecht, S. (2015) Three-Dimensional Vascular Network Assembly From Diabetic Patient-Derived Induced Pluripotent Stem Cells. Arteriosclerosis, Thrombosis, and Vascular Biology. 35(12):2677-85
Wang, G., Rajpurohit, S.K., Delaspre, F., Walker, S.L., White, D.T., Ceasrine, A., Kuruvilla, R., Li, R.J., Shim, J.S., Liu, J.O., Parsons, M.J., Mumm, J.S. (2015) First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic β-cell mass. eLIFE. 4
Gao, Y., Chan, R.H., Chow, T.W., Zhang, L., Bonilla, S., Pang, C.P., Zhang, M., Leung, Y.F. (2014) A High-Throughput Zebrafish Screening Method for Visual Mutants by Light-Induced Locomotor Response. IEEE/ACM transactions on computational biology and bioinformatics. 11(4):693-701
Wang, K., Milkie, D.E., Saxena, A., Engerer, P., Misgeld, T., Bronner, M.E., Mumm, J., Betzig, E. (2014) Rapid adaptive optical recovery of optimal resolution over large volumes. Nature Methods. 11(6):625-8
Mathias, J.R., Zhang, Z., Saxena, M.T., and Mumm, J.S. (2014) Enhanced Cell-Specific Ablation in Zebrafish Using a Triple Mutant of Escherichia Coli Nitroreductase. Zebrafish. 11(2):85-97
Zhang, L., Bonilla, S., Zhang, Y., and Leung, Y.F. (2014) p35 promotes the differentiation of amacrine cell subtype in the zebrafish retina under the regulation of egr1. Developmental Dynamics : an official publication of the American Association of Anatomists. 243(2):315-23
Zhang, L., Ma, P., Collery, R., Trowbridge, S., Zhang, M., Zhong, W., and Leung, Y.F. (2014) Expression profiling of the RPE in zebrafish smarca4 mutant revealed altered signals that potentially affect RPE and retinal differentiation. Molecular Vision. 20:56-72
Teng, Y., Xie, X., Walker, S., White, D.T., Mumm, J.S., and Cowell, J.K. (2013) Evaluating human cancer cell metastasis in zebrafish. BMC cancer. 13(1):453
White, D.T., and Mumm, J.S. (2013) The nitroreductase system of inducible targeted ablation facilitates cell-specific regenerative studies in zebrafish. Methods (San Diego, Calif.). 62(3):232-40
Li, Z., Zhang, L., and Leung, Y.F. (2013) Use of the zebrafish model to study refractive error. Expert Review of Ophthalmology. 8(1):1-3
Zhang, L., Cho, J., Ptak, D., and Leung, Y.F. (2013) The Role of egr1 in Early Zebrafish Retinogenesis. PLoS One. 8(2):e56108
Xie, X., Mathias, J.R., Smith, M.A., Walker, S.L., Teng, Y., Distel, M., Koster, R.W., Sirotkin, H.I., Saxena, M.T., and Mumm, J.S. (2012) Silencer-delimited transgenesis: NRSE/RE1 sequences promote neural-specific transgene expression in a NRSF/REST-dependent manner. BMC Biology. 10:93
Zhang, L., Chong, L., Cho, J., Liao, P.C., Shen, F., and Leung, Y.F. (2012) Drug Screening to Treat Early-Onset Eye Diseases: Can Zebrafish Expedite the Discovery?. Asia-Pacific Journal of Ophthalmology. 1(6):374-383
Kok, F.O., Taibi, A., Wanner, S.J., Xie, X., Moravec, C.E., Love, C.E., Prince, V.E., Mumm, J.S., and Sirotkin, H.I. (2012) Zebrafish rest regulates developmental gene expression but not neurogenesis. Development (Cambridge, England). 139(20):3838-3848
Mathias, J.R., Saxena, M.T., and Mumm, J.S. (2012) Advances in zebrafish chemical screening technologies. Future Medicinal Chemistry. 4(14):1811-1822
Li, Z., Ptak, D., Zhang, L., Walls, E.K., Zhong, W., and Leung, Y.F. (2012) Phenylthiourea specifically reduces zebrafish eye size. PLoS One. 7(6):e40132
Walker, S.L., Ariga, J., Mathias, J.R., Coothankandaswamy, V., Xie, X., Distel, M., Köster, R.W., Parsons, M.J., Bhalla, K.N., Saxena, M.T., and Mumm, J.S. (2012) Automated reporter quantification in vivo: high-throughput screening method for reporter-based assays in zebrafish. PLoS One. 7(1):e29916
Hensley, M.R., Emran, F., Bonilla, S., Zhang, L., Zhong, W., Grosu, P., Dowling, J.E., and Leung, Y.F. (2011) Cellular Expression of Smarca4 (Brg1)-regulated Genes in Zebrafish Retinas. BMC Developmental Biology. 11(1):45
Teng, Y., Xie, X., Walker, S., Saxena, M., Kozlowski, D.J., Mumm, J.S., and Cowell, J.K. (2011) Loss of Zebrafish lgi1b Leads to Hydrocephalus and Sensitization to Pentylenetetrazol Induced Seizure-Like Behavior. PLoS One. 6(9):e24596
Teng, Y., Xie, X., Walker, S., Rempala, G., Kozlowski, D.J., Mumm, J.S., and Cowell, J.K. (2010) Knockdown of zebrafish Lgi1a results in abnormal development, brain defects and a seizure-like behavioral phenotype. Human molecular genetics. 19(22):4409-4420
Ariga, J., Walker, S.L., and Mumm, J.S. (2010) Multicolor Time-lapse Imaging of Transgenic Zebrafish: Visualizing Retinal Stem Cells Activated by Targeted Neuronal Cell Ablation. Journal of visualized experiments : JoVE. (43)
Zhang, L., and Leung, Y.F. (2010) Microdissection of zebrafish embryonic eye tissues. Journal of visualized experiments : JoVE. (40)
Curado, S., Anderson, R.M., Jungblut, B., Mumm, J., Schroeter, E., and Stainier, D.Y. (2007) Conditional targeted cell ablation in zebrafish: A new tool for regeneration studies. Developmental Dynamics : an official publication of the American Association of Anatomists. 236(4):1025-1035
Mumm, J.S., Williams, P.R., Godinho, L., Koerber, A., Pittman, A.J., Roeser, T., Chien, C.B., Baier, H., and Wong, R.O. (2006) In vivo imaging reveals dendritic targeting of laminated afferents by zebrafish retinal ganglion cells. Neuron. 52(4):609-621
Godinho, L., Mumm, J.S., Williams, P.R., Schroeter, E.H., Koerber, A., Park, S.W., Leach, S.D., and Wong, R.O. (2005) Targeting of amacrine cell neurites to appropriate synaptic laminae in the developing zebrafish retina. Development (Cambridge, England). 132(22):5069-5079
Kay, J.N., Roeser, T., Mumm, J.S., Godinho, L., Mrejeru, A., Wong, R.O., and Baier, H. (2004) Transient requirement for ganglion cells during assembly of retinal synaptic layers. Development (Cambridge, England). 131(6):1331-1342