Faculty

Raymond C. Chan, Ph.D.
Assistant Professor

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Research Interests

Our laboratory research studies the role of higher-order structure and organization of chromosomes in fundamental biological processes in germ cells, including chromosome segregation, DNA damage repair, and germline maintenance. Proper organization of DNA is critical for the replication, repair and accurate segregation of genomic DNA. Specifically, we are focusing on the Structural Maintenance of Chromosomes (SMC) proteins, since SMC proteins are fundamental chromatin components that regulate higher-order chromosome organization. SMC proteins typically form multi-subunit complexes, and there are three types of SMC complexes conserved from yeast to human cells.

Working with the nematode Caenorhabditis elegans, we have applied a combination of high-resolution 3D microscopy, genetics and biochemistry to characterize two conserved SMC protein complexes in the proper packaging of meiotic chromosomes in the adult germline. Two emerging research areas for SMC studies focus on 1) how SMC proteins act locally within a chromosome to facilitate DNA damage repair, and 2) how SMC functions impact metazoan development. Humans with mutations in Smc and Smc-related genes exhibit birth defects and post-natal developmental dysfunctions. However, a significant barrier to the studies of SMC's role in development and in specific tissues stems from the essential needs for most SMC proteins for cellular division and viability during early development. We have identified a set of SMC proteins that are highly enriched in the nematode germ cells. We have also identified mutations in these smc genes that do no disrupt the viability of the mutant worms, providing the ideal system for the genetic and cell biological dissection of their germ cell functions.

Current research efforts in our lab will dissect the functions of these SMC proteins in the adult germline during gamete production and in the progenitor and developing germ cells in embryos and larvae. We are also applying genetics and biochemical methods to identify proteins that interact or associate with this SMC complex, in order to gain better insights into how the complex functions in a coordinated manner with other chromosome factors. Our research using this genetically tractable nematode model will have important implications for understanding how disruptions in these conserved chromosomal factors could contribute toward infertility, birth defects and developmental dysfunctions in humans.

Education

1987-1991 B.A., Molecular Biology Major, Pomona College, Claremont, CA.

1992-1997 Ph.D., Molecular Biology Institute, University of California, Los Angeles, CA Thesis Advisor: Douglas L. Black
Dissertation Title: The polypyrimidine tract binding protein mediates the splicing repression required for c-src neuronal-specific alternative pre-messenger RNA splicing.

1998-2006 Postdoctoral Research, University of California, Berkeley, CA Research Advisor: Barbara J. Meyer
Research Focus: The maintenance of genomic stability during cell division, using the nematode Caenorhabditis elegans as a model system to study the impact of higher order DNA architecture on chromosome segregation.

Honors and Awards

1990-1991 Research Laboratory Technician, Laboratory of Loren H. Rieseberg, Rancho Santa Ana Botanic Gardens, Claremont, CA

1991-1992 Research Associate, Cetus (Chiron) Corporation, Emeryville, CA.

1993-1996 Cellular and Molecular Biology Training Grant, UCLA

1996 Molecular Biology Institute Graduate Fellowship, UCLA

1999-2002 Leukemia and Lymphoma Society Postdoctoral Fellowship

2003-2006 Staff Research Associate, Laboratory of Barbara J. Meyer, UC Berkeley and HHMI

2006 Assistant Professor, University of Michigan Medical School

Recent Publications

Peer-Reviewed Journals and Publications

Rieseberg, L. H. , Choi, H., Chan, R., and Spore, C. (1993) Genomic map of a diploid hybrid species. Heredity 70, 285-293.

Min, H., Chan, R. C., and Black, D. L. 1995. The generally expressed hnRNP F is involved in a neural-specific pre-mRNA splicing event. Genes Dev.9: 2659-2671.

Chan, R. C. and Black, D. L. 1995. Conserved intron elements repress splicing of a neuron-specific c-src exon in vitro. Mol. Cell. Biol.15: 6377-6385.

Chan, R. C. and Black, D. L. 1997. The polypyrimidine tract binding protein binds upstream of neural cell-specific c-src exon N1 to repress the splicing of the intron downstream. Mol. Cell. Biol.17: 4667-76.

Chu, D. S., Dawes, H. E., Lieb, J. D., Chan, R. C., Kuo, A. F., and Meyer, B. J. 2002. A molecular link between gene-specific and chromosome-wide transcriptional repression. Genes Dev.16: 796-805.

Chan, R. C., Chan, A., Jeon, M., Wu, T. F., Pasqualone, D., Rougvie, A. E., and Meyer, B. J. 2003. Chromosome cohesion is regulated by a clock gene paralogue TIM-1. Nature423: 1002-1009.

Chan, R. C., Severson, A. F., and Meyer, B. J. 2004. Condensin restructures chromosomes in preparation for meiotic divisions. J. Cell Biol.167: 613-625.

Bickel, J.S., Chen, L., Hayward, J., Yeap, S.L., Alker, A.E., and Chan, R.C. 2010. Structural Maintenance of Chromosomes (SMC) proteins promote homolog-independent recombination repair in meiosis crucial for germ cell genomic stability. PLoS Genet. In press.

Verbrugghe, K. and Chan, R. C. Imaging C. elegans embryos using an epifluorescent microscope and open source software. J. Visualized Experiments. In Press

Jia, L., Bickel, J. S., Wu, J., Morgan, M. A., Li, H., Yang, J., Yu, X., Chan, R.C., and Sun, Y. (2010)
RBX1 (RING-Box Protein 1) E3 ubiquitin ligase is required for genomic integrity by modulating DNA
replication licensing proteins. J.Biol. Chem. In Press

Book Chapter

1. Black, D. L., Chan, R. C., Min, H., Wang, J., and Bell, L. 1998. The Electrophoretic Mobility Shift Assay for RNA Binding Proteins. In RNA:Protein Interactions: A Practical Approach (ed. C. W. J. Smith), pp. 109-136. Oxford University Press, Oxford.

Lab Members