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Adam Rich Ph.D.
Lennon Hall, Room B18, Tel: 395-5740
I use the zebrafish as a model system for human disease. We are developing a novel zebrafish-based model for human gastrointestinal (GI) motility. Zebrafish is a good model because of its transparency. We study the mechanisms that regulate coordinated GI motility, and focus on an important regulatory cell, the interstitial cell of Cajal (ICC). The ultimate goal is to use the zebrafish to develop new treatments for GI motility disorders.
Organogenesis is directly observable in zebrafish larvae. The GI tract is functional by 5 days post-fertilization (dpf) when larvae first swallow food. Spontaneous muscular contractions are observed at this stage, and the contractions become very regular by 7 dpf. We have shown that the zebrafish GI tract has ICC, and these ICC first appear by 7 dpf. Therefore patterns of coordinated motility and ICC develop concomitantly by 7 dpf. This observation is similar to what is observed in mice and in humans, and suggest that ICC are necessary to regulate GI motility.
The lab is beginning a new direction that will contribute to the understanding of development of ICC. Many common diseases (constipation, delayed gastric emptying) have been correlated with reduced ICC density. One current theory suggests that an imbalance between ICC apoptosis and ICC renewal results in reduced ICC density, contributing to GI motility disorders. Our lab will investigate the role of several genes on the development of ICC progenitor cells as well as maintenance of the ICC phenotype in adults. The overall objective is to better understand ICC turnover and to ultimately develop novel treatments that will restore ICC networks in humans.
Planned experiments will utilize real time PCR to examine the temporal expression patterns, and in-situ hybridization to examine spatial expression patterns for these genes. Fluorescence imaging and immunohistochemistry will quantify ICC density in intact tissues. Finally, functional GI motility experiments will quantify GI transit in living adult and larvae zebrafish, and spatiotemporal mapping experiments yield information about the development of coordinated motility patterns in larvae.
- A. Rich, S.A. Leddon, S.L. Hess, S.J. Gibbons, S. Miller, X. Xu, and G. Farrugia. Kit-like immunoreactivity in the Zebrafish gastrointestinal tract reveals putative ICC. Dev Dyn. 236: 903-11 (2007)
- A. Rich. A new high-content model system for studies of gastrointestinal transit: the zebrafish. Neurogastroenterology and Motility Neurogastroenterol Motil. 21: 225-8 (2009)
- J.L. Davis, X. Long, M.A. Georger, I.C. Scott, A. Rich, J.M. Miano. Identification and Characterization of Two Highly Conserved Serum Response Factor Genes in Zebrafish. Int J Dev Biol. 52: 389-96 (2008)
- V. Lamian, A. Rich, Z. Ma, J. Li, R. Seethala, D. Gordon, and Y. Dubaquie. Characterization of Agonist-Induced Motilin Receptor Trafficking and its Implications for Tachyphylaxis. Mol Pharmacol. 69: 109-18 (2006)
- A. Rich, S.M. Miller, S.J. Gibbons, J. Malysz, J.H. Szurszewski, G. Farrugia. Local presentation of Steel factor increases expression of c-kit immunoreactive interstitial cells of Cajal in culture. Am J Physiol Gastrointest Liver Physiol. 284: G313-20 (2003)