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Harold C. Smith, Ph.D.

Contact Information

Phone Numbers

Office: (585) 275-4267

Fax: (585) 275-6007

Research Labs

Faculty Appointments

Biography

Research

Normal and cancer cells express more diversity in proteins than can be accounted for by the predicted number of expressed genomic DNA sequence. Expansion of the genomically encoded expressed sequences through alternative processing of RNA, such as mRNA editing, is a logical hypothesis for how protein diversity and variations seen as tissue-specific and regulated expression of proteins can be achieved. The specific focus of the research is to identify and characterize novel mammalian mRNA editing systems that employ a zinc-dependent deamination mechanism for the post-transcriptional conversion of cytidine to uridine at select sites within mRNAs. Computational modeling has suggested a family of mammalian enzymes known as Cytidine Deaminases Active on RNA or CDARs as responsible for C to U editing of mRNAs.

The expression of these enzymes in biology suggests that mRNA editing may be involved in numerous physiological processes and could be manipulated for the prevention of cardiovascular disease, HIV infection and cancer, and is also necessary for production of antibodies in B lymphocytes. Recent evidence indicates that the enzyme involved in suppressing HIV-1 infectivity (CEM15) and the enzyme that promotes antibody production (AID) may act to mutate deoxy cytidine in DNA rather than or in addition to RNA.

Our research involves molecular biology and protein techniques, DNA microarray analyses and computational biology to identify the mRNAs that are edited by CDARs and to determine the biological consequence of these editing events in terms of the predicted changes in the types of protein structures and functions that can be expressed. Our studies have demonstrated how cytidine to uridine mRNA editing contributes to expansion in the diversity of expressed mRNA sequences known collectively as the transcriptome.

We are also evaluating the regulatory mechanisms controlling the expression of editing factors and their localization in the cell nucleus. The development of this new information will establish an important new annotation of the human genome that will serve as a frame of reference for studies of proteins involved in health and disease and mechanisms regulating their expression.

Credentials

Education

1975
BS | Purdue University
Biology

1978
MS | Purdue University
Veterinary Medicine

1980
MA | St Univ at Buffalo
Molecular Biology

1982
PhD | St Univ at Buffalo
Molecular Biology

Patents

Patent Title: Methods and Compositions Related to the Structure and Function of APOBEC3G
Patent #: 8,999,317
Issue Date: Apr 07, 2015
Country: United States
Invented By: Ryan P Bennett, Harold C Smith, Joseph E Wedekind

Patent Title: Methods and Compositions Related to the Structure and Function of APOBEC3G
Patent #: 2104516
Issue Date: Jan 07, 2015
Country: Europe
Invented By: Harold C Smith, Joseph E Wedekind

Patent Title: Methods and Compositions Related to the Structure and Function of APOBEC3G
Patent #: DE2104516
Issue Date: Jan 07, 2015
Country: Germany
Invented By: Harold C Smith, Joseph E Wedekind

Patent Title: Methods and Compositions Related to the Structure and Function of APOBEC3G
Patent #: GB2104516
Issue Date: Jan 07, 2015
Country: United Kingdom
Invented By: Harold C Smith, Joseph E Wedekind

Patent Title: Methods and Compositions Related to Heightened Apobec-1 Related Protein (ARP) Expression
Patent #: 2006338523
Issue Date: Jul 12, 2012
Country: Australia
Invented By: Andrew Brooks, Xia Jin, Harold C Smith

Patent Title: Methods and Compositions Related to APOBEC-1 Expression
Patent #: 2059122
Issue Date: Jun 20, 2012
Country: Europe
Invented By: Harold C Smith

Patent Title: Methods and Compositions Related to APOBEC-1 Expression
Patent #: FR2059122
Issue Date: Jun 20, 2012
Country: France
Invented By: Harold C Smith

Patent Title: Methods and Compositions Related to APOBEC-1 Expression
Patent #: DE602007023457.3
Issue Date: Jun 20, 2012
Country: Germany
Invented By: Harold C Smith

Patent Title: Methods and Compositions Related to APOBEC-1 Expression
Patent #: GB2059122
Issue Date: Jun 20, 2012
Country: United Kingdom
Invented By: Harold C Smith

Patent Title: Method and Compositions for Modifying Apolipoprotein B mRNA Editing
Patent #: 1392846
Issue Date: Jun 11, 2008
Country: Europe
Invented By: Harold C Smith

Patent Title: Method and Compositions for Modifying Apolipoprotein B mRNA Editing
Patent #: FR1392846
Issue Date: Jun 11, 2008
Country: France
Invented By: Harold C Smith

Patent Title: Method and Compositions for Modifying Apolipoprotein B mRNA Editing
Patent #: DE1392846
Issue Date: Jun 11, 2008
Country: Germany
Invented By: Harold C Smith

Patent Title: Method and Compositions for Modifying Apolipoprotein B mRNA Editing
Patent #: GB1392846
Issue Date: Jun 11, 2008
Country: United Kingdom
Invented By: Harold C Smith

Patent Title: Method and Compositions for Modifying Apolipoprotein B mRNA Editing
Patent #: NL 1392846
Issue Date: Jun 11, 2008
Country: Netherlands
Invented By: Harold C Smith

Patent Title: Method and Compositions for Modifying Apolipoprotein B mRNA Editing
Patent #: IT1392846
Issue Date: Jun 11, 2008
Country: Italy
Invented By: Harold C Smith

Patent Title: Human Immunodeficiency Virus Antiviral Screening Assay Involving the Detection of CEM15 Expression
Patent #: 8,841,068
Issue Date: Sep 23, 2014
Country: United States
Invented By: Andrew Brooks, Xia Jin, Harold C Smith

Patent Title: Drug Screening Via Nanopore Silicon Filters
Patent #: 8,501,668
Issue Date: Aug 06, 2013
Country: United States
Invented By: James L McGrath, Harold C Smith

Patent Title: Context-Dependent-Inhibitors of Cytidine Deaminases and Uses Thereof
Patent #: 8,158,770
Issue Date: Apr 17, 2012
Country: United States
Invented By: Harold C Smith, Joseph E Wedekind

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Publications

Journal Articles

8/2018
Salter JD, Smith HC. "Modeling the Embrace of a Mutator: APOBEC Selection of Nucleic Acid Ligands." Trends in biochemical sciences.. 2018 Aug 0; 43(8):606-622. Epub 2018 May 23.

5/2018
Bennett RP, Salter JD, Smith HC. "A New Class of Antiretroviral Enabling Innate Immunity by Protecting APOBEC3 from HIV Vif-Dependent Degradation." Trends in molecular medicine.. 2018 May 0; 24(5):507-520. Epub 2018 Mar 30.

9/2/2017
Smith HC. "RNA binding to APOBEC deaminases; Not simply a substrate for C to U editing." RNA biology.. 2017 Sep 2; 14(9):1153-1165. Epub 2016 Nov 21.

Books & Chapters

2008
Book Title: RNA and DNA Editing: Mechanisms and Their Impact on Biological Systems
Author List: J. Cruz-Reyes, J.D. Alfonzo, T. Meier, S. Maxwell, C. McElrevey, J.E. Wedekind, G.L. Verdine, B. Brown, E. Esinberg, S. Mass,, S. Lin, Y.-T. Yu, V. Blanc, N.O Davidson, M. Ohman, R. Harris, A.M. Sheehy, G. Carmichael
Published By: Wiley & Sons 2008

2007
Chapter Title: Determination of C to U Editing Activity in Cells and Biochemical Isolates
Book Title: methods in Enzymology
Author List: Smtih, Harold, C.
Edited By: Gott, J
Published By: Academic Press 2007

2006
Chapter Title: Editing Informational Content of Expressed DNA Sequences and Their Transcripts
Book Title: The Implicit Genome
Author List: Smith, Harold, C.
Edited By: Caporale, L.
Published By: Oxford University Press 2006

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