Person
Mumm, Jeff
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Biography and Research Interest
RESEARCH INTERESTS
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.
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.
Non-Zebrafish Publications
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.