David MacAlpine
Professor of Pharmacology and Cancer Biology
Overview
Our laboratory is interested in understanding the mechanisms by which the molecular architecture of the chromosome regulates fundamental biological processes such as replication and transcription. Specifically, how are replication, transcription and chromatin modification coordinated on a genomic scale to maintain genomic stability? We are addressing this question by using genomic, computational and biochemical approaches in the model organism Drosophila melanogaster.
DNA replication is an essential cell cycle event required for the timely and accurate duplication of chromosomes. Replication initiates at multiple sites (called origins of replication) distributed across each chromosome. The failure to properly regulate origin selection and activation may result in catastrophic genomic instability and potentially tumorigenesis. Recent metazoan genomic studies have demonstrated a correlation between time of DNA replication and transcriptional activity, with actively transcribed regions of the genome being replicated early. However, the underlying mechanism of this correlation remains unclear. By systematically characterizing the replication dynamics of multiple cell types, each with distinct transcriptional programs, we will be in a position to understand how these processes are coordinated.
Another goal of the laboratory is to identify the chromosomal features that direct and regulate metazoan DNA replication. Origins of DNA replication are marked by the formation of multi-protein complex, called the preRC. Despite conservation of the proteins that comprise the preRC in all eukaryotes, very little is known about the sequence elements required for the selection and regulation of metazoan origins. We are using genomic tiling microarrays to systematically map all the sites of preRC assembly in the Drosophila genome. The high resolution mapping of thousands of replication origins will provide an unprecedented opportunity to use both computational approaches and comparative genomics to identify cis-acting elements that may regulate replication.
Positions
Professor of Pharmacology and Cancer Biology in the School of Medicine
2021 School of Medicine
Professor of Biochemistry in the School of Medicine
2022 School of Medicine
Professor of Cell Biology in the School of Medicine
2022 School of Medicine
Member of the Duke Cancer Institute in the School of Medicine
2006 School of Medicine
Education
Ph.D. 2001
2001 University of Texas Southwestern Medical Center, Medical School
Publications, Grants & Awards
- Grants (25)
- Academics Articles (66)
- Conference Pages (1)
- Book Sections (1)
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
University of North Carolina - Chapel Hill
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
American Society for Pharmacology and Experimental Therapeutics
American Cancer Society, Inc.
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Cancer Institute
American Cancer Society, Inc.
National Institutes of Health
National Institutes of Health
National Institutes of Health
Genome Research
Genes Dev
Nucleic Acids Res
Nature Communications
Nucleic Acids Res
Nucleic Acids Res
Proc Natl Acad Sci U S A
Molecular and Cellular Biology
Molecular and Cellular Biology
The Embo Journal
Genome Res
Genome Biology
Cold Spring Harbor Perspectives in Biology
Curr Biol
Dev Dyn
Genome Research
Proc Natl Acad Sci U S A
Genes & Development
Crit Rev Biochem Mol Biol
Genome Research
Genes & Development
Genes & Development
Genome Research
Plos Biology
The Embo Journal
Genes & Development
Proceedings of the National Academy of Sciences of the United States of America
Molecular Biology of the Cell
Proceedings of the National Academy of Sciences of the United States of America
Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology
Genes & Development
Genes & Development
The Journal of Cell Biology
The Embo Journal
Proceedings of the National Academy of Sciences of the United States of America
Molecular Biology of the Cell
Molecular and Cellular Biology
Molecular and Cellular Biology
Plant Physiology
The Initiation of DNA Replication in Eukaryotes
Offices & Contact
Durham, NC
27710 LSRC C333
Durham, NC
27710