U.S. Department of Health and Human Services

 Contact Info

Tel: 301-594-3285
Email: charlesj@niddk.nih.gov

 Select Experience

  • Ph.D.University of Maryland1995
  • M.S.Clemson University1983

 Related Links


    • Molecular Biology/Biochemistry
    Research Summary/In Plain Language

    Research Summary

    Research Goal

    My research goal is to clarify the biochemistry of L1 ORF1p by showing which peptide segments in the enzyme’s amino acid sequence bind RNA.  The purpose is to shed light on the underlying biochemistry of retrotransposition and its mutagenic effects, which have led to numerous genetic diseases.

    Current Research

    Retrotransposons, mainly LINE1 (L1) and SINES, account for about 40 percent of the human genome and have played major roles in genome evolution, yet the biochemistry of L1 replication is not understood.  ORF1p, one of two enzymes encoded in L1, is a nucleic acid–binding protein that acts as a nucleic acid chaperone in in vitro assays, and has been shown to be required for successful retrotransposition in cell culture assays.  How ORF1p functions in retrotransposition is largely unknown.  In particular, how the relationship between the in vitro nucleic acid binding and chaperone properties of the protein are related to its role in retrotransposition in vivo is not clear.  Thus, we have isolated retrotransposition negative mutants of the protein that are seemingly indistinguishable from the active protein in terms of both nucleic acid binding and chaperone activity.  This means that our biochemical understanding of the protein is incomplete, and one of my current goals is to define more precisely how the protein interacts with nucleic acids in vitro.  To this end, I am now determining what regions of the protein make contact with nucleic acids and whether these contacts are altered in the retrotransposition defective ORF1p proteins.​

    Applying our Research

    A recent review of the field (Beck et al. (2011), Annu. Rev. Genomics Hum. Genet., 12) estimated that retrotransposition-induced alterations in human genomes are responsible for one of every 1,000 spontaneous, disease-producing mutations in humans.  Basic research on the biology and biochemistry of these DNA-altering events informs the ongoing clinical research on these diseases.

    Need for Further Study

    Areas of retrotransposon biology in need of further study include the insertion mechanism whereby the copied retrotransposon reinserts into the genome, the manner in which mutagenic activity accompanies retrotransposition events, and, from an evolutionary standpoint, how the human “host” has managed to control the ongoing, mostly deleterious activity of LINE1 elements throughout human history.