1. Olfactomedin Project: As a neuroscience laboratory, our lab studies on the role of olfactomedin 2 protein using zebrafish as a model system. Similar to other proteins in the olfactomedin family, our functional analysis demonstrated that olfactomedin 2 plays key roles in the early nervous system development. These important functions include (i) branchiomotor neuronal axon guidance, (ii) cranial neural crest cell differentiation, and (iii) late-onset vasculogenesis of the brain. We are currently working to identify molecular mechanisms for olfactomedin 2 functions. We believe that our olfactomedin 2 research on these critical aspects will shed new light on our mechanistic understanding of the early brain development.
2. Alzheimer’s Disease Project: Collaboration between Dr. Gregory Cole’s and our lab has produced the first zebrafish transgenic fish line, which expresses Green Fluorescent Protein by the zebrafish expression elements of the most intensively studied Alzheimer’s Disease gene, amyloid precursor protein (APP). This transgenic fish line will be used to screen environmental toxins and potential drug candidates in a high-throughput screening, which will be of importance for the better understanding and even development of medicine for Alzheimer’s Disease. We are currently developing another transgenic zebrafish line with a human mutant form of APP, which could be used as the first zebrafish model of Alzheimer’s Disease. The importance of this project was recently recognized and funded by the North Carolina Biotechnology Center.
3. Other Collaboration Projects: We have also developed a collaboration with Dr. Somnath Mukhopadhyay’s laboratory, in which we study the role of the main Marijuana receptor, CB1R, in early vessel development using zebrafish (presented in 2007 Vasculata conference). In addition, Dr. Gordon Ibeanu at BRITE institute and our laboratory are working together to develop an efficient bioassay technology using zebrafish to conduct a high-throughput screening for drug candidates for Huntington’s Disease.
Methodology: We are currently using state-of-the-art molecular, cellular, imaging, and bioinformatics technologies and constantly developing new methods, which include, but not limited to, DNA cloning, gene expression in live animals by microinjection and electroporation, genetic knockdown via RNAi and morpholino, cDNA microarray, immunohistochemistry and in situ hybridization, cell culture and transfection, extensive use of microscopy, and a diverse array of bioinformatic tools for computational biology. Personally, I am currently in charge of the maintenance of and education for the use of BBRI’s Zeiss LSM510 Multiphoton Laser Confocal Microscope.
Recent PublicationsLee, J.-A. and Cole, G.J. (2007) Generation of transgenic zebrafish expressing green fluorescent protein under control of zebrafish amyloid precursor polypeptide gene regulatory elements. Zebrafish. 2007 Winter;4(4):277-86
Lee, J.-A., Anholt, R.R. H. and Cole, G.J. (2008). Olfactomedin-2 mediates development of the anterior central nervous system in zebrafish. Mechanisms of Development, 125(1-2):167-81
Kim, M.J., Liu, I.-H., Song, Y., Lee, J.-A., Halfter, W., Balice-Gordon, R.J., Linney, E., and Cole, G.J. (2007). Agrin is required for posterior development and motor axon outgrowth and branching in embryonic zebrafish. Glycobiology 17, 231-247.
Wakamatsu, Y., Nakamura, N., Lee, J.-A., Cole, G.J., and Osumi, N. (2007) Transitin, a Nestin-like intermediate filament protein, mediates cortical localization and lateral transport of Numb in mitotic avian neuroepithelial cells. Development 134, 2425-2433.