Gene Regulation and Chromosome Biology Laboratory

Chief
Jeffrey N. Strathern, Ph.D.
Deputy Chief
Mikhail Kashlev, Ph.D.

The Gene Regulation and Chromosome Biology Laboratory includes research in a variety of organisms, notably bacteriophage lambda, Escherichia coli, Saccharomyces cerevisiae, and Schizosaccharomyces pombe. This research is unified by interests in chromosome dynamics (recombination, chromosome segregation, and transposable elements) and regulation (transcription, silencing, and cell cycle control).

Dr. Strathern's laboratory is focused on the fidelity of recombination and transcription. They demonstrated that DNA synthesis associated with recombination is relatively low fidelity.The investigators identified mutations that elevate the level of aberrant genome rearrangements including DNA palindromes and developed ways to clone and sequence these palindromes. Their research in transcription is focused on the isolation of mutations that increase the error rate during mRNA synthesis.

Dr. Klar's laboratory studies the positional silencing and the site-specific recombination mechanisms that are components of cell type switching in S. pombe. Their studies have revealed several novel genes involved in establishing or maintaining epigenetic states of gene expression. They are also characterizing a strand-specific genome marking system that programs cell type switching. In addition, Dr. Klar's laboratory studies the segregation of DNA strand in mammals using mouse models.

Dr. Court's laboratory has demonstrated that the N gene of bacteriophage lambda exhibits two different levels of regulation on lambda genes: N binds to its own mRNA and inhibits the synthesis of more N protein, and it modifies RNA polymerase so that transcription continues through termination sites into downstream genes. The laboratory staff is investigating how these two mechanisms are related and what other cellular functions contribute to these processes. They developed an improved method for genetic engineering in E. coli.  This technique, known as recombineering, has been adopted to facilitate site directed mutagenesis and genetic engineering in mouse models.

Dr. Kashlev's laboratory, established in August 1996, is elucidating the role of RNA polymerase in transcription elongation and termination in E. coli. The lab is also carrying out an investigation of transcription elongation and fidelity in yeast and in E. coli .

Dr. Jin's laboratory studies RNA polymerase (RNAP), RNAP-associated proteins including RapA that is a Swi2/Snf2 protein and regulation of transcription using simple model system Escherichia coli. They are studying the effects of nutrient starvation and other stress responses on the distribution of RNAP and structure of bacterial chromosome. In collaboration with several PIs in GRCBL, Dr. Jin also isolates and characterizes RNAP mutants defective in transcription fidelity. Recently, his laboratory initiated a basic research on Helicobacter pylori pathogenesis.

Dr. Gu’s laboratory is focused on the mechanisms of RNA interference and microRNA pathways, and their applications in cancer treatment. MiRNAs play essential roles in gene regulation networks, human diseases and cancer. They study the mechanisms of miRNA biogenesis, post-transcriptional modifications, turnover and biological functions in mammalian systems. This information will then be used to test novel RNA-based approaches designed to alter gene expression with improved safety, off-targeting, and potency profiles, which can then be used as tools for biological discovery and therapeutics.

Dr. Zheng's laboratory is focused on RNA cis-elements and protein-RNA interactions in regulation of viral and host gene expression in various infections with tumorviruses, including high-risk human papillomaviruses and Kaposi sarcoma-associated herpesvirus. This study aims to understand how RNA processing and non-coding RNAs are involved in viral carcinogenesis. The long-term goal is to identify biomarkers for clinical diagnosis and to develop strategies to control viral or host gene expression.

About

The Gene Regulation and Chromosome Biology Laboratory includes research in a variety of organisms, notably bacteriophage lambda, Escherichia coli, Saccharomyces cerevisiae, and Schizosaccharomyces pombe. This research is unified by interests in chromosome dynamics (recombination, chromosome segregation, and transposable elements) and regulation (transcription, silencing, and cell cycle control).

Dr. Strathern's laboratory is focused on the fidelity of recombination and transcription. They demonstrated that DNA synthesis associated with recombination is relatively low fidelity.The investigators identified mutations that elevate the level of aberrant genome rearrangements including DNA palindromes and developed ways to clone and sequence these palindromes. Their research in transcription is focused on the isolation of mutations that increase the error rate during mRNA synthesis.

Dr. Klar's laboratory studies the positional silencing and the site-specific recombination mechanisms that are components of cell type switching in S. pombe. Their studies have revealed several novel genes involved in establishing or maintaining epigenetic states of gene expression. They are also characterizing a strand-specific genome marking system that programs cell type switching. In addition, Dr. Klar's laboratory studies the segregation of DNA strand in mammals using mouse models.

Dr. Court's laboratory has demonstrated that the N gene of bacteriophage lambda exhibits two different levels of regulation on lambda genes: N binds to its own mRNA and inhibits the synthesis of more N protein, and it modifies RNA polymerase so that transcription continues through termination sites into downstream genes. The laboratory staff is investigating how these two mechanisms are related and what other cellular functions contribute to these processes. They developed an improved method for genetic engineering in E. coli.  This technique, known as recombineering, has been adopted to facilitate site directed mutagenesis and genetic engineering in mouse models.

Dr. Kashlev's laboratory, established in August 1996, is elucidating the role of RNA polymerase in transcription elongation and termination in E. coli. The lab is also carrying out an investigation of transcription elongation and fidelity in yeast and in E. coli .

Dr. Jin's laboratory studies RNA polymerase (RNAP), RNAP-associated proteins including RapA that is a Swi2/Snf2 protein and regulation of transcription using simple model system Escherichia coli. They are studying the effects of nutrient starvation and other stress responses on the distribution of RNAP and structure of bacterial chromosome. In collaboration with several PIs in GRCBL, Dr. Jin also isolates and characterizes RNAP mutants defective in transcription fidelity. Recently, his laboratory initiated a basic research on Helicobacter pylori pathogenesis.

Dr. Gu’s laboratory is focused on the mechanisms of RNA interference and microRNA pathways, and their applications in cancer treatment. MiRNAs play essential roles in gene regulation networks, human diseases and cancer. They study the mechanisms of miRNA biogenesis, post-transcriptional modifications, turnover and biological functions in mammalian systems. This information will then be used to test novel RNA-based approaches designed to alter gene expression with improved safety, off-targeting, and potency profiles, which can then be used as tools for biological discovery and therapeutics.

Dr. Zheng's laboratory is focused on RNA cis-elements and protein-RNA interactions in regulation of viral and host gene expression in various infections with tumorviruses, including high-risk human papillomaviruses and Kaposi sarcoma-associated herpesvirus. This study aims to understand how RNA processing and non-coding RNAs are involved in viral carcinogenesis. The long-term goal is to identify biomarkers for clinical diagnosis and to develop strategies to control viral or host gene expression.

PI & Key Staff

Contact Info

Gene Regulation and Chromosome Biology Laboratory
Center for Cancer Research
National Cancer Institute
Building 539, Room 152
Frederick, MD 21702-1201
301-846-1225