Meng-Chao Yao

Appointments and Affiliations

 
 
Fred Hutchinson Cancer Research Center
Basic Sciences
Member
 
University of Washington
College of Arts and Sciences
Zoology
Affiliate Professor, Appointed: 1988
Professional Headshot of Meng-Chao  Yao

Mailing Address

1100 Fairview Ave. N.
P.O. Box 19024
Fred Hutchinson Cancer Research Center
Mailstop A2-025
Seattle, Washington 98109-1024
United States

Contact

Phone: (206) 667-4294
Fax: (206) 667-6522
http://www.imb.sinica.edu.tw/~mcyao/

 

Degrees

Ph.D., University of Rochester, Biology, 1975.

Research Interests

Gene amplification, DNA rearrangements and chromosome instability in eukaryotes.

My laboratory uses the ciliate Tetrahymena and other eukaryotes including yeast and mammalian cells to study the mechanisms of DNA rearrangements, gene amplification and other processes that affect the integrity and transmission of eukaryotic genomes. Tetrahymena is particularly suited for these studies because it carries out a remarkable series of DNA rearrangements during somatic nuclear differentiation, including massive chromosome breakage, telomere formation and DNA deletion, as well as specific gene amplification. Recently we have identified several critical cis-acting sequences involved in these processes, including a 15 bp sequence necessary and sufficient for chromosome breakage, two sets of sequences that promote DNA deletion and specify deletion boundaries, and a pair of inverted repeats essential for large DNA palindrome formation during gene amplification. This information set the stage for further investigation of the underlying molecular mechanisms. We have also begun to identify proteins involved in these processes and found a novel protein pdd1p that shows close cytological and physically association with the deleted DNA during the process. This protein contains two chromodomains and is thought to play a key role in re-organizing chromatin during DNA rearrangements. Reverse genetics studies have shown that the protein is needed for successful nuclear differentiation and DNA deletion. In order to identify additional proteins, we have recently established a method to screen for proteins that are localized in developing nuclei, and have identified ten additional novel genes. We are determining their roles in DNA rearrangements and/or nuclear differentiation. Most recently, we have shown that the deletion process can remove inserted foreign sequences, and probably serves to defend the genome against invading genetic agents. Furthermore, injection of double stranded RNA triggers DNA deletion, demonstrating a mechanistic link between DNA deletion and RNA intereference that occur widely among eukaryotes.

At least one mechanism of DNA rearrangements discovered in Tetrahymena has also been found to occur in other organisms. We have shown that giant DNA palindromes can be produced in budding yeast by introducing a double stranded DNA break next to a pair of short inverted repeats, just like in Tetrahymena. This finding suggests a common mechanism for generating amplified genetic elements in eukaryotes. We have now successfully tested this idea using Chinese hamster ovary cells, and begun to examine the role of this mechanism in gene amplification and cancer progression.

Additional Experience

The biogenesis and function of ribosomal RNA.

Languages

(Reading, Writing, Speaking)

Chinese, Mandarin: (Fluent, Functional, Fluent)

Memberships

American Association for the Advancement of Science
American Society for Cell Biology
Society of Protozoologists

Honors and Awards

Fellow, American Association for the Advancement of Science (AAAS)

Previous Positions

1978-1986, Assistant and Associate Professor, Washington University in St. Louis, Arts and Sciences, Biology

Patents

Ribosomes as vectors for RNA, Patent Number: 5739310, 1998, Institution-owned, United States of America.

Funding

  • National Cancer Institute: Pilot Project: A new approach to gene amplification in tumor cells., Jan 1, 2001 to Dec 31, 2002.
  • National Cancer Institute: Training Grant: Chromosome metabolism and cancer, 1991 to 2006.
  • NIH R01 GM26210: Chromosome Breakage and DNA Deletion in Tetrahymena, 1979 to 2006.

 

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