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Harold Smith, Ph.D.

Photo of Harold Smith
Scientific Focus Areas: Cell Biology, Chromosome Biology, Computational Biology, Developmental Biology, Genetics and Genomics, Systems Biology

Professional Experience

  • Ph.D., Columbia University, 1995
  • M.Phil., Columbia University, 1994
  • M.A., Columbia University, 1990

Research Goal

My field of research is the determination of stem cell fate. I seek to understand the regulation of gene expression that gives rise to a specific type of cell. My model of choice is the germ line of the nematode Caenorhabditis elegans, which produces both sperm and egg.

Current Research

The laboratory provides next-generation sequencing (NGS) service for the NIDDK community. In my own research, NGS is a tool to define patterns of cell-type-specific gene expression, to characterize chromatin modifications associated with that expression, and to identify mutations that alter cell fate or function. We also use these NGS data sets for the development and implementation of bioinformatics software for analysis pipelines.

Applying our Research

Stem cells possess the unique ability to develop into other types of cells. The mechanisms that underlie this ability might one day be harnessed for the treatment of developmental defects and degenerative diseases.

Need for Further Study

Currently, we do not understand many of the rules that govern cell fate determination, which limits our ability to apply stem cell treatment toward specific therapeutic ends.

Select Publications

Mutation frequency is not increased in CRISPR-Cas9-edited mice.
Willi M, Smith HE, Wang C, Liu C, Hennighausen L.
Nat Methods (2018 Oct) 15:756-758. Abstract/Full Text
A Genetic Analysis of the Caenorhabditis elegans Detoxification Response.
Fukushige T, Smith HE, Miwa J, Krause MW, Hanover JA.
Genetics (2017 Jun) 206:939-952. Abstract/Full Text
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Research in Plain Language

We determine the sequence of DNA and RNA samples. These data allow us to identify genetic variations or mutations that cause or influence disease, to determine the targets of DNA-binding proteins, and to identify which genes are turned on or off. We also develop software that allows us to extract this information from the sequence data.