|Business Address:||Division of Biology, 156-29|
|California Insititute of Technology|
|Pasadena, California 91125|
|Phone: (818) 395-4988; Fax: (818) 583-8351|
|Email address: Cathy@mirsky.caltech.edu|
|Ph. D.||National Yang-Ming Medical College Institute of Micrology and Immunology||1987-1992||Molecular Virology|
|B. S.||Fu-Jen CatholicUniversity||1983-1987||Biology|
|Teaching Assistant||National Yang-Ming Medical College||1989-1991||Microbiology and Immunology|
|Research Fellow in Biology||California Insititute of Technology||1992-1995||Molecular Developmental Biology|
|Senior Research Fellow in Biology||California Insititute of Technology||1995-present||Molecular Developmental Biology|
|Research Associate||Stowers Institute of Medical Research||1996-present||Molecular Developmental Biology|
1. Rank First Scholarship Award, Fu-Jen Catholic
2. Research Fellowship, Taiwan National Science Council
3. Wang Ming-Ning Scholorship, Wang Ming-Ning Memorial Fundation
1st of the comptitors, December 28, 1991.
4. Procter and Gamble Fellowship, Caltech
August, 1992 to August, 1993
5. Gordon Ross Fellowship, Caltech
August, 1993 to August, 1995.
6. Biology Divisional Fellowship, Caltech
August, 1994 to August, 1995
Oral Presentations and Posters
1. Yuh, C. H. and Ting, L. P.
"Human Hepatitis B Virus Contains Second Enhancer" (Oral)
The Twenty Thirdth Annual Meeting of the Chinese Society of Microbiology. December 10, 1989.
2. Yuh, C. H. and Ting, L. P.
"Identification of the Second Enhancer in the Human Hepatitis B Virus and Its Action Mechanism" (Oral)
The Fifth Joint Annual Conference of Biomedical Sciences. April 7-8, 1990.
3. Yuh, C. H., Chang, Y. L. and Ting, L. P.
"Action Mechanism of the Second Enhancer of Human Hepatitis B Virus" (Oral)
The Sixth Molecular Biology Retreat. September 6-8, 1990.
4. Yuh, C. H., Lee, S. C. and Ting, L. P.
"Cooperation Between II-A and II-B Regions of the Human Hepatitis B Viral Second Enhancer" (Poster)
The First Asian Conference on Transcription (ACT-I). December 6-8, 1990.
5. Yuh, C. H. and Ting, L. P.
"Dural Regulatory Roles of 106-bp Sequence on Gene Expression of Hepatitis B Virus" (Oral)
The Sixth Joint Annual Conference of Biomedical Sciences. March 23-24, 1991.
6. Yuh, C. H. and Ting, L. P.
"Functional Organization of the HBV Second Enhancer: C/EBP-Like Proteins Binding to the Box-a and Box-b Elements and Cooperation of the two Elememts Is Required for Its Function" (Oral)
The Seventh Joint Annual Conference of Biomedical Sciences. March 21-22, 1992.
7. Yuh, C. H. and Davidson, E. H.
"Transcriptional Regulation of Endo 16 in the Sea Urchin Embryo" (Oral) The Forfth Southwest Transcription Factor Meeting. May 5-6, 1995.
8. Yuh, C. H. and Davidson, E. H.
"Complex Spatial and Temporal Transcriptional Regulation of an Endoderm-Specific Marker Gene in the Sea Urchin Embryo" (Oral) The Fifth Biology Annual Retreat of Caltech. October 20-22, 1995.
9. Yuh, C. H. and Davidson, E. H.
"Modular Cis-Regulatory Organization of Endo16, a Gut-Specific Gene of the Sea Urchin Embryo " (Poster) The Research Directors Conference of Caltech. Febulary 1, 1996.
10. Yuh, C. H. and Davidson, E. H.
"Mutagensis analysis of Endo 16 Promoter" (Oral) The Sixth Biology Annual Retreat of Caltech. October 20-22, 1996.
11. Yuh, C. H. and Davidson, E. H.
"Quantitative investigation and Mutagensis analysis of Endo 16 Promoter" (Oral) The Fifth Southwest Transcription Factor Meeting, Nov. 15-16, 1996.
12. Yuh, C. H. and Davidson, E. H.
" The interaction and output of the functional elements in the module A of Endo 16 Promoter" (Oral) The Sixth Southwest Transcription Factor Meeting, Apr. 11-12, 1997.
1. Chang, H. K., Wang, B. Y., Yuh, C. H.,
Wei, C. L. and Ting, L. P.
A Liver-Specific Nuclear Factor Interacts with the Promoter Region of the Large Surface Protein Gene of the Human Hepatitis B virus. Mol. Cell Biol. 9: 5189-5197, 1989.
2. Yuh, C. H. and Ting,
Cooperation of Two Elements within the Second Enhancer of the Human Hepatitis B viral Genome in "Viral Hepatitis and Liver Disease" p. 176-182, Harper Graphics, Inc. Waldorf, MD. 1990.
3. Yuh, C. H. and Ting, L. P.
The genome of the Hepatitis B virus Contains a Second Enhancer: Cooperation of Two Elements within This Enhancer Is Required for Its Function. J. of Virol. 64: 4281-4287, 1990.
4. Yuh, C. H. and Ting, L. P.
C/EBP-like Proteins Binding to the Functional Box-a and Box-b of the Second Enhancer of Hepatitis B Virus. Mol. Cell Biol. 11: 5044-5052, 1991.
5. Yuh, C. H. Chang, Y. L.and Ting, L.
Transcriptional Regulation of the Precore and Pregenomic RNAs of Hepatitis B Virus. J. of Virol. 66: 4073-4084, 1992.
6. Yuh, C. H. and Ting, L. P.
Differentiated Liver Cell Specificity of the Second Enhancer of Hepatitis B Virus. J. of Virol. 67: 142-149, 1993.
7. Yuh, C. H., Ransick, A., Martinez, P., Britten, R. J.
and Davidson, E. H.
Complexity and Organization of DNA-Protein Interactions in the 5’-Regulatory Region of an Endoderm-Specific Marker Gene in the Sea Urchin Embryo. Mech. Development. 47: 165-186, 1994.
8. Wang, H. D., Yuh, C. H., Dang, C.V., and Johnson
The Hepatitis B Virus X Protein Increases the Cellular Level of TATA-binding Protein which Mediates Transactivation of RNA Polymerase III Genes. Mol. Cell. Biol.,15: 6720-6728, 1995.
9. Yuh, C. H. and Davidson, E. H.
Modular Cis-Regulatory Organization of Endo16, a Gut-Specific Gene of the Sea Urchin Embryo.. Development. 122, 1069-1082, 1996.
10. Kirchhamer, C. V., Yuh, C. H. and Davidson, E.
Modular Cis-Regulation of Developmentally Expressed Genes: Two Genes Transcribed Territorially in the Sea Urchin Embryo, and Additional Examples. Proc. Natl. Acad. Sci. USA. 93, 9322-9328, 1996.
11. Yuh, C. H., Moore, J. G. and Davidson, E.
Quantitative Functional Interrelations within the Cis-Regulatory System of the S. purpuratus Endo16 Gene. Development. 122, 4045-4056, 1996.
A fundamental question in biology today concerns how complex tissue-specific and inducible gene expression is regulated. In eukaryotes, it is often difficult to ascribe specific roles to individual regulatory molecules or signal transduction pathways when several cues impinge simultaneously on a given gene. The net gene expression, therefore, must relate to the relative combinations of various transcription factors and accessory proteins, both positive and negative, tissue-specific and ubiquitous, that bind to the target DNA at any one time. I have attempted to elucidate the regulation of Endo16, a lineage specific, differentially regulated gene of the sea urchin embryo, as a model system to dissect these events. My primary goal is to make significant and pivotal contributions to our understanding of the molecular mechanisms which govern this process.
I received my Ph.D. degree in the Graduate Institute of Microbiology & Immunology at National Yang-Ming Medical college in Taiwan. My thesis work involved characterization of the mechanism of action of the second enhancer and the core promoter of the Hepatitis B virus. I discovered that the genome of Hepatitis B virus contains a second enhancer, and the cooperation of two elements within this enhancer is required for its function. Furthermore, I purified and characterized the transcription factors responsible for this tissue-specific enhancer . This work have was published in six papers in major journals. My training provided me with a strong background in molecular biology and biochemistry. At Caltech, I was awarded the Gordon Ross post-doctoral fellowship in 1992. I chose to work with Dr. Eric Davidson, since his laboratory has been studying early developmental gene regulation in sea urchin. Research in this field would allow me to acquire the use of embryology techniques, and would tremendously facilitate my ability to examine the complex transcriptional regulation of a lineage-specific gene in early development.
During the past four years I have been studying transcription regulation of the Endo16 gene in the sea urchin. The expression of the Endo16 gene is confined to the definitive vegetal plate at blastula stage. Expression is continuous throughout the archenteron at gastrula stage, and by 72 hr is found only in the midgut. To investigate the lineage-specific regulation of Endo16, I have analyzed the DNA-binding proteins that bind to the upstream regulatory region of this gene. Mapping studies of the 2.3 Kb upstream region required for correct regulation in transgenic embryo have revealed thirty-eight sites of highly specific DNA-protein interaction. A complete series of oligonucleotide gel shift cross-competitions among the target sites was carried out and revealed nine "unique" factors and five "common" factors that occupy to those sites. The target sites appear to be organized in a sequence of modules around unique factors. (Yuh et al., Mech. Development. 47: 165-186, 1994).
The regulatory region of Endo16 gene can be divided into seven modules, from A ( proximal) to G (distal), each one of which has one unique factor and many common factors binding on it. They are separated from each other by a region of non-protein binding spacer. To investigate the regulatory function of the seven Endo16 promoter modules in vivo, I generated a series of reporter constructs in which the bacterial chloramphenicol acetyltransferase (CAT) gene is under the control of specific Endo16 promoter modules, and then injected these constructs into fertilized eggs. The embryos were used to assay the level of the CAT activity, and others were processed for localization of CAT message by whole-mount in situ hybridization. I discovered that the regulation of Endo16 gene expression can be divided into two phases. The early phase of Endo16 regulation directly reflects vegetal plate specification. During this phase module A primarily establishes the transcription of Endo16 in vegetal plate, while modules B and G can cooperate with module A to strengthen this activity. Modules E and F negatively regulate expression in ectodermal cells and module DC negatively regulates expression in primary mesenchyme cells. These negative function modules are sensitive to LiCl treatment, since LiCl treatment results in ectopic Endo16 expression. The late phase of Endo16 regulation controls stomach specific expression. Module B is the major module for regulating stomach specific expression ( Yuh et. al.,Development. 122, 1069-1082, 1996). These studies have elucidated an important modular regulatory organization. This is a major feature of gene regulation molecular biology. Recombinations among modular regulatory regions resulting in novel patterns of developmental gene expression may play an important role in evolution.