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Harold Smith is a tenured professor of biochemistry and biophysics at the University of Rochester, School of Medicine and Dentistry. Dr. Smith's primary function at the University is basic research and in this context he is fully engaged in biomedical laboratory research as well as training postdocs, graduate and undergraduate students.
The Smith lab's primary interest is understanding the composition, regulation and structure of macromolecular complexes involved in regulating gene expression at the level of messenger RNA expression and processing. Our focus is on a platform of enzymes that change the genetic code at the DNA or RNA level by deaminating cytidine to form uridine. Current data suggest that this family of cytidine deaminase function with other proteins (auxiliary proteins) as holoenzymes complexes which we refer to as editosomes (for RNA) or mutasomes (for DNA). RNA editing or DNA mutational activity by these enzymes affect the protein coding capacity of mRNAs and thereby can diversify the proteins that are expressed by cells (the proteome).
The lab is harnessing the power of molecular engineering, genomics, protein biochemistry and cell biology to address how the activity and specificity of these enzymes are controlled by cells such that only select nucleic acids are affected, at the appropriate time and only in appropriate cells. Proper regulation of enzyme expression and activity is important for normal biological responses such as anti-viral host cell defense, dietary lipid transport in the blood and enabling a specific and robust immune response. Conversely, when these enzymes are not expressed or their activity is blocked or inappropriately activated, diseases may be acquired such as AIDS, atherosclerosis, cancer and immunodeficiency.
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