Christopher Nicchitta
Professor of Cell Biology
Overview
Our laboratory studies the cellular architecture and regulation of protein synthesis, with the goal of understanding how cells regulate the subcellular organization and temporal dynamics of protein synthesis. We focus on mRNA localization - the process by which cells control where and when a protein is synthesized by localizing its mRNA to a discrete location(s) in the cell. Such regulation is critical for many aspects of cell dynamics, cell signaling and cell division. Of the diverse mRNA localization phenomena that have been identified to date, the most prominent is mRNA localization to the endoplasmic reticulum (ER). mRNA localization to the ER operates on an unusually large scale (essentially the entire mRNA transcriptome is partially represented on the ER, with those mRNAs encoding secretory and membrane proteins being highly ER-enriched), and continuously– all newly exported mRNAs undergo selection for translation in the cytosol and/or the ER compartments.
We use a broad array of experimental approaches - biochemistry, cell biology, genomics, and computational biology - and are focusing on several related themes. First, we are working to identify the mRNA-encoded signals used to target mRNAs to the ER as well as the cellular factors that recognize these signals. One mechanism, in which a signal in nascent secretory and membrane proteins directs mRNA recruitment to the ER, has been previously described. It is clear though that there are multiple pathways that direct mRNAs to the ER, including pathways that direct cytosolic and nucleoplasmic protein-encoding mRNAs to the ER. We are also investigating how, once localized, mRNAs are anchored to the ER membrane. In a recent study, we reported that the cohort of mRNAs encoding organelle resident proteins(e.g., nuclear envelope, ER, Golgi, lysosomes, peroxisomes) are localized tothe ER and directly anchored to components of the ER membrane. We are very interested in understanding the cis-encoded anchoring signals and the integral membrane proteins that function in mRNA anchoring to biological membrane, and lastly, how direct mRNA anchoring influences mRNA translation and mRNA stability.
In parallel efforts, we discovered that mRNA translation is under distinct regulatory control in the cytosol and ER compartments, with translation being 3-5 fold more efficient on the ER. These differences are substantial and suggest that mRNA localization to the ER may represent an important post-transcriptional gene expression mechanism. To gain insight into the mechanisms and factors responsible for the compartmental regulation of mRNA translation we are using traditional biochemical approaches (pulse-labeling, cell fractionation, immunoprecipitation, proteomics) as well as genomic approaches (ribosome footprinting, deep sequencing).
Positions
Professor of Cell Biology in the School of Medicine
2008 School of Medicine
Associate Dean of Research Training in the School of Medicine
2014 School of Medicine
Associate Professor of Pathology in the School of Medicine
2007 School of Medicine
Professor of Biochemistry in the School of Medicine
2009 School of Medicine
Member of the Duke Cancer Institute in the School of Medicine
1993 School of Medicine
Education
Ph.D. 1987
1987 University of Pennsylvania
Publications, Grants & Awards
- Grants (32)
- Academics Articles (124)
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
American Heart Association
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
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
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
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
Nature Communications
Proc Natl Acad Sci U S A
Semin Cell Dev Biol
Molecular & Cellular Proteomics : Mcp
International Journal of Doctoral Studies
Cbe Life Sciences Education
Cbe Life Sciences Education
The Journal of Biological Chemistry
Molecular and Cellular Biology
Journal of Visualized Experiments : Jove
Nat Rev Mol Cell Biol
The Journal of Biological Chemistry
Curr Biol
Cell Host Microbe
J Am Chem Soc
The Journal of Cell Biology
The Journal of Biological Chemistry
Mol Biochem Parasitol
Molecular Biology of the Cell
Cell Biol Int
The Journal of Immunology
J Immunol
Immunity
Molecular Biology of the Cell
Methods in Molecular Biology (Clifton, N.J.)
Methods in Enzymology
The Journal of Biological Chemistry
Trends in Immunology
Bioorganic & Medicinal Chemistry Letters
Protein Science : a Publication of the Protein Society
Rna (New York, N.Y.)
Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire
Molecular Biology of the Cell
Cancer Research
Molecular Cell
The Journal of Gene Medicine
The Journal of Biological Chemistry
The Journal of Immunology
Cell Stress and Chaperones
The Journal of Biological Chemistry
The Embo Journal
Rna (New York, N.Y.)
The Journal of Clinical Investigation
The Journal of Biological Chemistry
Nature Reviews. Immunology
Current Opinion in Immunology
The Journal of Experimental Medicine
Proceedings 50th ASMS Conference on Mass Spectrometry and Allied Topics
Current Opinion in Cell Biology
The Journal of Biological Chemistry
The Journal of Biological Chemistry
The Journal of Immunology
Traffic (Copenhagen, Denmark)
Current Topics in Membranes
Traffic (Copenhagen, Denmark)
The Journal of Biological Chemistry
Trends in Cell Biology
The Journal of Biological Chemistry
The Journal of Biological Chemistry
The Journal of Biological Chemistry
International Journal of Molecular Medicine
The Journal of Biological Chemistry
The Journal of Biological Chemistry
Immunological Investigations
The Journal of Biological Chemistry
Essays in Biochemistry
The Journal of Biological Chemistry
Journal of Cell Science
The Journal of Immunology
Chemtracts
Current Opinion in Immunology
The Journal of Cell Biology
The Journal of Biological Chemistry
The Journal of Cell Biology
The Journal of Biological Chemistry
The Journal of Biological Chemistry
Biochemistry
Protein Expression and Purification
Seminars in Cell & Developmental Biology
The Journal of Cell Biology
Molecular Biology of the Cell
The Journal of Biological Chemistry
The Journal of Cell Biology
Methods in Cell Biology
Proceedings of the National Academy of Sciences of the United States of America
Cell
The Journal of Cell Biology
Biochimica Et Biophysica Acta
The Biochemical Journal
The Journal of Pharmacology and Experimental Therapeutics
Febs Letters
The Journal of Biological Chemistry
The Journal of Biological Chemistry
Analytical Biochemistry
Federation Proceedings
Comparative Biochemistry and Physiology Part B: Comparative Biochemistry
Offices & Contact
Durham, NC
27708 Duke Box 3709
Durham, NC
27710