Victor Ambros

Academic Role: Professor

Faculty Appointment(s) In:
   Interdisciplinary Graduate Program
   Program in Molecular Medicine

Molecular and genetic control of animal development; microRNA regulatory mechanisms

We are interested in the genetic regulatory mechanisms that control animal development, and in particular the molecules that function during animal development to ensure the proper timing of developmental events. We have primarily employed the nematode Caenorhabditis elegans as a model system for studying the function of regulators of developmental timing, which in C. elegans are known as the “heterochronic genes”, in  reference to the remarkable changes in relative timing of developmental event that are elicited by mutations in these genes. The heterochronic genes comprise a set of interrelated regulatory pathways that include proteins that regulate the transcription of other genes, and also a class of small RNA, known as microRNAs, that regulate the production of protein by the messenger RNAs of specific target genes. Much of our research in recent years has been aimed at understanding how microRNAs are integrated into broader regulatory networks related to animal development and human disease, and at uncovering the molecular mechanisms for how microRNAs exert their effects on gene expression. 

Publications

Ambros V, Horvitz HR. (1984) Heterochronic mutants of the nematode Caenorhabditis elegans. Science. Oct 26;226(4673):409-16.

Ambros V. (1989)A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans. Cell. Apr 7;57(1):49-57.

Lee, R., Feinbaum, R., and Ambros, V. (1993).  The heterochronic gene lin-4 of C. elegans encodes small RNAs with antisense complementarity to lin-14.  Cell, 75, 843-854.

Moss, E., Lee, R., and Ambros, V. (1997) Control of developmental timing by the cold shock domain protein Lin-28 and its regulation by the lin-4 RNA. Cell 88, 637-646.

Olsen, P. H. and Ambros, V. (1999) The lin-4 regulatory RNA controls developmental timing in C. elegans by blocking LIN-14 protein synthesis after the initiation of translation.  Develop Biol. 216,671-680

Lee, R. C. and Ambros, V. (2001) An extensive class of small RNAs in Caenorhabditis elegans. Science 294, 862-864

Lee, R.C., Hammell C.H., Ambros V.R. (2006) Interacting endogenous and exogenous RNAi pathways in C. elegans. RNA, Apr;12(4):589-97

Gaur, A.B. , Jewell, D.A.,  Liang, Y., Ridzon, D. , Moore, J.H. Chen, C., Ambros,V. R. and Israel, M. A.  (2007). Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res 67: (6). 2456-2468.

Long, D., Lee, R., Williams, P.,  Chan, C.Y., Ambros,V. and Ding, Y. (2007). Potent Effect of Target Structure in MicroRNA Function. Nature Struct Mol Biol. 14; 287-294.

Hinas, A, Reimegård, J. Wagner, E.G.H., Nellen, W., Ambros, V.R. and Söderbom, F. (2007) The small RNA repertoire of the unicellular amoeba Dictyostelium discoideum: microRNA candidates, small antisense RNAs that may be derived from longer transcripts and multiple classes of repeat-associated RNAs. Nucleic Acids Research 2007;35(20):6714-26.

Miska, E. A., Alvarez-Saavedra, E., Abbott, A. L., Lau, N. C., Hellman, A. B., McGonagle, S. M., Bartel, D. P., Ambros, V.R. and Horvitz, H. R. (2007) Most Caenorhabditis elegans microRNAs are individually not essential for development or viability. PLoS Genet. 2007 Dec 14;3(12):e215

Sokol, N. S., Xu, P., Jan, Y. N., and Ambros, V. (2008) Drosophila let- 7 microRNA is required for remodeling of the neuromusculature during  metamorphosis. Genes and Devel. In press

Rotations

Project 1: Genetic screens for proteins that modify or regulate the activity of microRNAs in C. elegans.

Project 2: Yeast 2-hybrid screens for proteins that interact with the microRNA machinery. 

Project 3: Microscopic analysis of the effects of C. elegans microRNA gene mutations on the neural development and function.

Project 4: Computational analysis of microRNA target interactions.

Personnel

Rosalind Lee, Research Associate/Lab Manager

Christopher Hammell, Postdoctoral Fellow

Molly Hammell, Postdoctoral Fellow

Maria Ow, Postdoctoral Fellow

Xantha Karp, Postdoctoral Fellow

Anna Zinovyeva, Postdoctoral Fellow

Omid Harandi, Postdoctoral Fellow

Biography

Victor Ambros grew up in Vermont and graduated from MIT in 1975. He did his graduate research (1976-1979) with David Baltimore at MIT, studying poliovirus genome structure and replication. He began to study the genetic pathways controlling developmental timing in the nematode C. elegans as a postdoc in H. Robert Horvitz's lab at MIT, and continued those studies while on the faculty of Harvard (1984-1992), Dartmouth (1992-2007), and the University of Massachusetts Medical School (2008-present).  In 1993, members of the Ambros lab identified the first microRNA, the product of lin-4, a heterochronic gene of C. elegans. Since then, the role of microRNAs in development has been a major focus of his research.

Office: Biotech II - Suite #306
Phone: (508) 856-6380
Fax: (508) 856-4289
E-mail: Victor.Ambros@umassmed.edu

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