Nicholas Marsh-Armstrong, Ph.D.
Kennedy Krieger Institute
707 N. Broadway
Baltimore, MD 21205
Dr. Nicholas Marsh-Armstrong is a research scientist at the Kennedy Krieger Institute. He is also an associate professor in the Department of Neuroscience at Johns Hopkins University School of Medicine.
Dr. Marsh-Armstrong graduated magna cum laude with his bachelor's degree in chemistry and philosophy at Haverford, where he won the Undergraduate Award in Analytical Chemistry. He went on to pursue graduate work in neuroscience and cellular and developmental biology at Harvard, receiving his doctoral degree in 1994. He then served as a post-doctoral fellow at the Carnegie Institution of Washington in the Department of Embryology until early this year, when he came to Hopkins and Kennedy Krieger Institute as an assistant professor.
Dr. Marsh-Armstrong was the recipient of the Certificate of Distinction in Teaching at Harvard in 1991, and was a recipient of a Howard Hughes Medical Institute pre-doctoral fellowship and a Jane Coffin Childs Memorial Fund for Medical Research post-doctoral fellowship.
During development, a symphony of gene expression sets up the structure and function of the nervous system. Dr. Marsh-Armstrong's lab focuses on the use of transgenic technologies to shed light on the rules that govern developmental gene regulation in the nervous system. His ultimate goal is to understand how aberrant gene regulation leads to developmental disorders.
To date, Dr. Armstrong's efforts have been directed at studying amphibian metamorphosis. A tadpole’s transformation into an adult frog is an example of a complex developmental gene regulatory program that is choreographed by a single molecule, thyroid hormone. In one frog species, Xenopus laevis, the surge in thyroid hormone at metamorphosis produces changes in proliferation and cell death throughout the nervous system, and results in the emergence of new neural structures, new physiology and new behavior.
More recently, Dr. Marsh-Armstrong has turned his attention to human gene regulation, taking advantage of the high-throughput nature of transgenesis in Xenopus frogs and the wealth of information emerging from the completion of the human genome. Transgenic studies in mice have been successful in studying questions of gene regulation on a gene-by-gene basis, but transgenic methodology in mice is laborious and expensive. Dr. Marsh-Armstrong has shown that using Xenopus laevis frogs, an individual researcher can generate daily hundreds of transgenic animals easily and inexpensively. Mammalian promoters expressed in Xenopus show the same expression pattern that they show in mice. This makes Xenopus an ideal vertebrate model organism in which to conduct a high-throughput transgenic study of human gene regulation.
Dr. Marsh-Armstrong's immediate goal is to produce "reporter frogs" for 1000 human genes, concentrating on neural genes already implicated in human disease, or genes whose function is known or presumed to be involved in the regulation of transcription. Commercially available clones that have large (approximately 200kb) fragments of human genomic DNA cloned in bacterial artificial chromosomes (BACs) will be made into vital reporter constructs by inserting the green fluorescent protein (GFP) using efficient recombination technology in bacteria. Since these frogs' embryonic development occurs externally, animals transgenic for these GFP-tagged BACs will report when and where the human genes are expressed during development. Expression patterns seen in transgenic frogs will be related to the phenotypes of genetic disorders that map near the chromosomal sites of origin for the BACs. Further, families of animals carrying these transgenes will become powerful tools to perform further high-throughput screens for genes and other molecules that regulate the expression of human genes.
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