ZFIN ID: ZDB-PERS-010214-1
Mumm, Jeff
Email: jmumm3@jhmi.edu
URL: http://www.hopkinsmedicine.org/profiles/results/directory/profile/3310512/jeffrey-mumm
Affiliation: Mumm Lab
Address: Johns Hopkins School of Medicine Wilmer Eye Institute Smith Bldg, Rm 4015 400 N Broadway Baltimore, MD, 21287 USA
Country: United States
Phone: (410) 502-2210


Cellular Regeneration

To advance studies of cellular regeneration – as opposed to tissue 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.

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
Rich, M.H., Sharrock, A.V., Mulligan, T.S., Matthews, F., Brown, A.S., Lee-Harwood, H.R., Williams, E.M., Copp, J.N., Little, R.F., Francis, J.J.B., Horvat, C.N., Stevenson, L.J., Owen, J.G., Saxena, M.T., Mumm, J.S., Ackerley, D.F. (2023) A metagenomic library cloning strategy that promotes high-level expression of captured genes to enable efficient functional screening. Cell chemical biology. 30(12):1680-1691.e6
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
Shao, W., Chang, M., Emmerich, K., Kanold, P.O., Mumm, J.S., Yi, J. (2022) Mesoscopic oblique plane microscopy with a diffractive light-sheet for large-scale 4D cellular resolution imaging. Optica. 9:137413851374-1385
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
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
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
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
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
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
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
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
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)
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

Journal Article:

Saxena M.T., Schroeter E.H., Mumm J.S., Kopan R. (2001). Murine Notch homologs (N1-4) undergo presenilin-dependent proteolysis. Journal of Biological Chemistry, 276: 40268-40273.

Mumm, J.S., Schroeter, E.H., Saxena, M.T., Griesemer, A., Tian, X., Pan, D.J., Ray, W.J., and Kopan, R. (2000). A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1. Mol. Cell 5, 197-206.

Huppert, S., Le, A., Schroeter, E., Mumm, J.S., Saxena, M.T., Milner, L., and R. Kopan (2000). Embryonic lethality in mice homozygous for a processing deficient Notch1 allele. Nature 405, 966-970.

Ray, W.J., Yao, M., Mumm, J., Schroeter, E.H., Saftig, P., Wolfe, M., Selkoe, D.J., Kopan, R. and A. M. Goate (1999). Cell surface presenilin-1 participates in the gamma-secretase-like proteolysis of Notch. J. Biol. Chem., 274, 36801-36807.

De Strooper, B., Annaert, W., Cupers, P., Saftig, P., Craessaerts, K., Mumm, J.S., Schroeter, E.H., Schrijvers, V., Wolfe, M.S., Ray, W.J., Goate, A., and R. Kopan (1999). A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature. 398: 518-522.

Ray, W.J., Yao, M., Nowotny, P., Mumm, J., Zhang, W., Wu, J.Y., Kopan, R., and A. M. Goate (1999). Evidence for a physical interaction between Presenilin and Notch. Proc. Natl. Acad. Sci. USA. 96: 3263-3268.

Calof, A.L., Mumm, J.S., Rim, P.C, and J. Shou (1998). The neuronal stem cell of the olfactory epithelium. Jour. Neurobio. 36: 190-205.

Mumm, J.S., Shou, J. and A.L. Calof (1996). Colony-forming progenitors from mouse olfactory epithelium: Evidence for feedback regulation of neuron production. Proc. Natl. Acad. Sci. USA. 93: 11167-11172.

Calof, A.L., Hagiwara, N., Holcomb, J., Mumm, J.S. and J. Shou (1996). Neurogenesis and cell death in olfactory epithelium. Jour. Neurobio. 30: 67-81.

Gordon, M.K., Mumm, J.S., Davis, R.A., Holcomb, J.D. and A.L. Calof (1995). Dynamics of MASH1 expression in vitro and in vivo suggest a non-stem cell site of MASH1 action in the olfactory receptor neuron lineage. Mol. Cell. Neuro. 6: 363-379.

Holcomb. J.D., Mumm, J.S., and A.L. Calof (1995). Apoptosis in the neuronal lineage of the mouse olfactory epithelium: Regulation in vitro and in vivo. Develop. Bio. 172: 307-323.

Book Chapters and Reviews:

Mumm, J.S. and C. Lohmann (2006). Dendritic growth. In: Retinal Development, E. Sernagor, S. Eglen, W. Harris, and R. Wong, eds. (Cambridge University Press, New York), pp. 242-264.

Mumm, J.S., Godinho, L., Morgan, J.L., Oakley, D.M., Schroeter, E.H., and R.O.L. Wong (2005). Laminar circuit formation in the vertebrate retina. In: Development, Dynamics and Pathology of Neuronal Networks: From Molecules to Functional Circuits, Progress in Brain Research, vol. 147, J. van Pelt , M. Kamermans, C.N. Levelt, A. van Ooyen , G.J.A. Ramakers, P.R. Roelfsema, eds. (Elsevier BV, Amsterdam, The Netherlands), pp. 155-169.

Lohmann, C., Mumm, J., Godinho, L., Schroeter, E., Stacy, R., Wong, W.T., Oakley, D., and Wong, R.O.L. (2005). Live imaging of the developing retina. In: Imaging in Neuroscience and Development, R. Yuste, and A. Konnerth, eds. (Cold Spring Harbor Laboratory Press), pp. 171-183.

Kopan, R., Huppert, S., Mumm, J.S., Saxena, M.T., Schroeter, E.H., Ray, W.J., and Goate, A. (2001). The NEXT step in Notch processing and its relevance to Amyloid Precursor Protein. In: Neurodegenerative disorders: loss of function through gain of function, K. Beyreuther, Y. Christen, and C.L. Masters, eds. (Springer-Verlag, New York), pp. 119-128.

Mumm, J.S., and R. Kopan (2000). Notch signaling: From the outside in. Develop. Bio. 228: 151-165.

Calof, A.L., Mumm, J.S., Rim, P.C, and J. Shou (1999). In vitro analysis of neuronal progenitors from mouse olfactory epithelium. In: The Neuron in Tissue Culture (L. Haynes, ed.) Wiley, Chichester.

Calof, A.L., Rim, P.C, Askins, K,J., Mumm, J.S., Gordon, M.K., Iannuzzelli, P., and J. Shou (1998). Factors regulating neurogenesis and programmed cell death in mouse olfactory epithelium. In: Olfaction and Taste XII (C. Murphy, ed.) Ann. N.Y. Acad. Sci. 855: 226-229.

Calof, A.L., Holcomb, J.D., Mumm, J.S., Hagiwara, N., Tran, P., Smith, K.M., and D. Shelton (1996). Factors affecting neuronal birth and death in the mammalian olfactory epithelium. In: Growth Factors as Drugs for Neurological and Sensory Disorders. Wiley, Chichester, (Ciba Foundation Symposium No. 196): 188-210.

Calof, A.L., Adusumalli, M.D., Dehamer, M., Guevara, J.L., Mumm, J.S., Whitehead S.J. and A.D. Lander (1994). Generation, differentiation, and maturation of olfactory receptor neurons in vitro. In: Olfaction and Taste XI (K. Kurihara, N. Suzuki, H Ogawa, eds.) Tokyo, Springer-Verlag: 36-40.