Shannon Fisher, M.D., Ph.D.
Assistant Professor of Cell and Developmental Biology
Department: Cell and Developmental Biology
Graduate Group Affiliations
Contact information
1213 BRB II/III
421 Curie Blvd.
Philadelphia, PA 19104
421 Curie Blvd.
Philadelphia, PA 19104
Office: (215) 898-7886
Fax: (215) 898-9871
Fax: (215) 898-9871
Email:
sfisher4@mail.med.upenn.edu
sfisher4@mail.med.upenn.edu
Publications
Education:
B.S. (Chemistry)
Purdue University, 1985.
MD
Johns Hopkins University, 1993.
Ph.D. (Neuroscience)
Johns Hopkins University, 1993.
Permanent linkB.S. (Chemistry)
Purdue University, 1985.
MD
Johns Hopkins University, 1993.
Ph.D. (Neuroscience)
Johns Hopkins University, 1993.
Description of Research Expertise
Research InterestsSkeletal development in the vertebrate embryo; transcriptional regulation and genome evolution
Key words
zebrafish, bone, cartilage, transcription factors, comparative genomics
Description of Research
The patterning and formation of the skeleton lends form and function to all vertebrate organisms; the maintenance and remodeling of bone in the adult is a striking example of tissue homeostasis via stem cells. We are taking genetic and cellular approaches in the zebrafish to understand both the early events in skeletal development and the regeneration of bone in the adult after injury. We have developed lines of transgenic zebrafish expressing fluorescent proteins in bone and cartilage, allowing us to visualize the establishment of the skeleton in live fish. We have also developed a method to trace cell lineages in the zebrafish, and used it to establish the contribution of neural crest to the skeleton.
Double transgenic embryo expressing egfp in cartilage and rfp in bone.
GFP expression marks neural crest descendents in a 2-day zebrafish embryo.
A second area of focus is in comparative genomics, examining how the sequences regulating transcription of important skeletal genes have evolved and function in diverse organisms. We have developed a highly efficient approach using zebrafish transgenesis to identify and study regulatory sequences, from the genomes of zebrafish and of distantly related species like human and mouse. We are applying this approach on a large scale to identify enhancers that control expression in skeletal tissues. These regulatory elements provide insight into the signaling pathways that control bone and cartilage formation, and variants in their sequence and function are likely to contribute to human diseases affecting the skeleton.
Rotation projects
Identify the regulatory elements for a gene important in skeletal development or associated with a human genetic disease, using zebrafish transgenesis
Describe an aspect of bone and cartilage formation using time-lapse microscopy, in wild-type or mutant zebrafish
Build and test constructs to aid in development of new technologies to manipulate the zebrafish genome
Lab personnel
Evanthia Pashos, graduate student
Gui Hu, research specialist
Michael Gallagher, research specialist
Selected Publications
Kague, E., Bessling, S. L., Lee, J., Hu, G., Passos-Bueno, M. R., Fisher, S.: Functionally conserved cis-regulatory elements of COL18A1 identified through zebrafish transgenesis. Developmental Biology 337(2): 496-505, January 2010.Brown, A. M., Fisher, S., Iovine, M. K.: Osteoblast maturation occurs in overlapping proximal-distal compartments during fin regeneration in zebrafish. Developmental Dynamics 238(11): 2922-8, November 2009.
Gerdes, Jantje M. Liu, Y, Zaghloul, Norann A. Leitch, Carmen C. Lawson, Shaneka S. Kato M. Beachy, Philip A. Beales, Philip L. DeMartino, GN, Fisher, Shannon. Badano Jose L. Katsanis Nicolas: Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response. Nature Genetics 39(11): 1350-60, Nov 2007.
J Xie, Jing. SL Bessling, TK Cooper, HC Dietz, AS McCallion, and S Fisher: Manipulating mitotic recombination in the zebrafish embryo through RecQ helicases. Genetics 176(2): 1339-42, Jun 2007.
S. Fisher, EA Grice, RM Vinton, SL Bessling, and AS McCallion: Conservation of RET regulatory function from human to zebrafish without sequence similarity. Science 312(5771): 276-9, Apr 14 2006.
Fisher, Shannon. Grice, Elizabeth A. Vinton, Ryan M. Bessling, Seneca L. Urasaki, Akihiro. Kawakami, Koichi. McCallion, Andrew S.: Evaluating the biological relevance of putative enhancers using Tol2 transposon-mediated transgenesis in zebrafish. Nature Protocols 1(3): 1297-305, 2006.
JL Badano, CC Leitch, SJ Ansley, H May-Shimera, S Lawson, RA Lewis, PL Beales, HC Dietz, S Fisher, and N Katsanis: Dissection of epistasis in oligogenic Bardet-Biedl syndrome. Nature 439: 326-330, 2006.
J Xie and S Fisher: Twisted gastrulation enhances BMP signaling through chordin dependent and independent mechanisms. Development 132(2): 383-91, Jan 2005.
Fisher, S. Halpern, M E.: Patterning the zebrafish axial skeleton requires early chordin function.[see comment]. Nature Genetics 23(4): 442-6, Dec 1999.
S Fisher, P Jagadeeswaran, and M. Halpern: Radiographic analysis of zebrafish skeletal defects. Developmental Biology 264(1): 64-76, Dec 1 2003.
Ross, Alison J. May-Simera, Helen. Eichers, Erica R. Kai, Masatake. Hill, Josephine. Jagger, Daniel J. Leitch, Carmen C. Chapple, J Paul. Munro, Peter M. Fisher, Shannon. Tan, Perciliz L. Phillips, Helen M. Leroux, Michel R. Henderson, Deborah J. Murdoch, Jennifer N. Copp, Andrew J. Eliot, Marie-Madeleine. Lupski, James R. Kemp, David T. Dollfus, Helene. Tada, Masazumi. Katsanis, Nicholas. Forge, Andrew. Beales, Philip L.: Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates.[erratum appears in Nat Genet. 2005 Dec;37(12):1381]. Nature Genetics 37(10): 1135-40, Oct 2005.
M Vega Flores, VWK Tsang, W Hu, MKalev-Zylinska, J Postlethwait, P Crosier, K Crosier, and S Fisher: Duplicate zebrafish runx2 orthologues are expressed in developing skeletal elements. Gene Expression Patterns 4(5): 573-81, Sep 2004.