Harold Smith (scientist)

Last updated
Harold C. Smith Jr.
Harold C Smith - 2010.jpg
Dr Smith in 2010
Born(1954-02-05)February 5, 1954
Münich, Germany
NationalityAmerican
Alma materPurdue University, SUNY at Buffalo
Known forRNA editing
SpouseJenny ML Smith
Children3
Scientific career
FieldsMolecular Biology, Biochemistry, RNA Biology, Drug discovery, Higher Education
InstitutionsOyaGen, University of Rochester
WebsiteAcademic website www.haroldsmithlab.com
Company Website www.oyageninc.com

Harold C. Smith Jr. (born February 5, 1954) is an American scientist, researcher, professor, founder and CEO of OyaGen. [1] [2] Smith has written over 100 publications on his research in RNA editing, AIDS, oncology, and immunodeficiency, among others.

Contents

Early life

Harold Smith was born in Germany to an Austrian mother and American father who was stationed in Austria with the military at the end of World War II. [3] In 6th grade, Smith and his family moved from Frankfurt, Germany, to Massachusetts, where he completed his high school education. [3]

Education

Smith received his Bachelor of Arts in Biology in 1975 and his Master of Science in Veterinary Pharmacology and Physiology in 1978 at Purdue University. [4] He then went to the State University at Buffalo where he obtained his Masters of Arts in Molecular Biology in 1980 and his PhD in Molecular Biology in 1982. [4] He carried out postdoctoral studies at SUNY Buffalo and Baylor College of Medicine in Houston, Texas. [3] [4]

Career

After completing his postdoctoral position with Dr. Susan Berget at Baylor College of Medicine in Biochemistry in 1986, Smith became an assistant professor at the University of Rochester. Between 1991 and 1994, Smith discovered the molecular mechanism by which proteins recognize messenger RNA and participate in site-specific assembly of enzyme complexes to orchestrate the modification of select cytidines to uridines in a process known as C to U RNA Editing. [5] This work has served as the foundation for numerous findings concerning RNA sequence modifying mechanisms and DNA mutating mechanisms that determine cell and protein diversification and was cited for its groundbreaking ideas in an article written by L. Chan for Scientific American. [6] In 1992, he was given an associate professorship with a limited tenure, which became fully tenured in 1996. In that time, he was also the director of graduate studies in the Department of Pathology. In 1994, Smith organized an Albany Research Conference which was the first international meeting focused on RNA editing and in 1997, Smith organized and chaired the first Gordon Conference for RNA Editing. [3] [5] From 1997 to 1998 he served as the director of Medical School Biochemistry in Cell Structure and Function, and subsequently as director of Molecules to Cells in the Double Helix Medical School Curriculum. In 2001, Smith became a full professor. [7] He received more than $8 million in total funding over the following 12 years from the National Institutes of Health (NIH) and other agencies. [7]

Harold Smith founded OyaGen, Inc., in 2003. [8] OyaGen is a biopharmaceutical company which develops therapies to fight viral illness through editing enzymes, with a focus on Human Immunodeficiency Virus (HIV). [3] [9] Founded with a seed fund by the University of Rochester and the Trillium Group, Smith has successfully brought in $6.5 million in Angel investment and $2.1 million in total federal grant support for OyaGen. [10] In 2005, the company began preclinical trials on a drug that OyaGen believes will protect the body's natural A3G, which functions as an editing enzyme in mutating HIV DNA during its replication in such a way that the virus can no longer code for itself. [11] In 2008, he edited a book for Wiley and Sons on RNA and DNA Editing that brought together the next generation of scientists working in the field to comment on their work and the future of the field. [12] That same year, Smith, through the University of Rochester Medical Center, received a $100 thousand grant from the Bill & Melinda Gates Foundation to aid in research for curing infectious diseases, such as HIV. [13] The New York State Common Retirement Fund invested in OyaGen in 2006 and again in 2010. [14] In February 2013, Cannabis Science, Inc. added Smith to its scientific advisory board. [10] He was added to IGXBio's Scientific Advisory Board in 2014, as well as the Education Board at the American Health Council in August 2016. [15] [16] He continues as a professor at the University of Rochester, School of Medicine and Dentistry, teaching biochemistry and biophysics. [4] Throughout his academic career, Smith has provided his expertise in reviewing grant proposals for the NIH as well as European and Israeli funding agencies.

Selected publications

Personal life

Smith met his wife, Jenny, during his sophomore year at Purdue. They have three children, Owen, Hanna and Sam.[ citation needed ]

Related Research Articles

Deamination is the removal of an amino group from a molecule. Enzymes that catalyse this reaction are called deaminases.

<span class="mw-page-title-main">Activation-induced cytidine deaminase</span> Enzyme that creates mutations in DNA

Activation-induced cytidine deaminase, also known as AICDA, AID and single-stranded DNA cytosine deaminase, is a 24 kDa enzyme which in humans is encoded by the AICDA gene. It creates mutations in DNA by deamination of cytosine base, which turns it into uracil. In other words, it changes a C:G base pair into a U:G mismatch. The cell's DNA replication machinery recognizes the U as a T, and hence C:G is converted to a T:A base pair. During germinal center development of B lymphocytes, error-prone DNA repair following AID action also generates other types of mutations, such as C:G to A:T. AID is a member of the APOBEC family.

<span class="mw-page-title-main">RNA editing</span> Molecular process

RNA editing is a molecular process through which some cells can make discrete changes to specific nucleotide sequences within an RNA molecule after it has been generated by RNA polymerase. It occurs in all living organisms and is one of the most evolutionarily conserved properties of RNAs. RNA editing may include the insertion, deletion, and base substitution of nucleotides within the RNA molecule. RNA editing is relatively rare, with common forms of RNA processing not usually considered as editing. It can affect the activity, localization as well as stability of RNAs, and has been linked with human diseases.

<span class="mw-page-title-main">APOBEC3G</span> Protein and coding gene in humans

APOBEC3G is a human enzyme encoded by the APOBEC3G gene that belongs to the APOBEC superfamily of proteins. This family of proteins has been suggested to play an important role in innate anti-viral immunity. APOBEC3G belongs to the family of cytidine deaminases that catalyze the deamination of cytidine to uridine in the single stranded DNA substrate. The C-terminal domain of A3G renders catalytic activity, several NMR and crystal structures explain the substrate specificity and catalytic activity.

<span class="mw-page-title-main">ADAR</span> Mammalian protein found in Homo sapiens

The double-stranded RNA-specific adenosine deaminase enzyme family are encoded by the ADAR family genes. ADAR stands for adenosine deaminase acting on RNA. This article focuses on the ADAR proteins; This article details the evolutionary history, structure, function, mechanisms and importance of all proteins within this family.

<span class="mw-page-title-main">APOBEC1</span> Protein-coding gene in the species Homo sapiens

Apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 also known as C->U-editing enzyme APOBEC-1 is a protein that in humans is encoded by the APOBEC1 gene.

<span class="mw-page-title-main">Cytidine deaminase</span> Protein-coding gene in the species Homo sapiens

Cytidine deaminase is an enzyme that in humans is encoded by the CDA gene.

<span class="mw-page-title-main">APOBEC3F</span> Protein-coding gene in the species Homo sapiens

DNA dC->dU-editing enzyme APOBEC-3F is a protein that in humans is encoded by the APOBEC3F gene.

<span class="mw-page-title-main">APOBEC3C</span> Protein-coding gene in humans

DNA dC->dU-editing enzyme APOBEC-3C is a protein that in humans is encoded by the APOBEC3C gene.

<span class="mw-page-title-main">APOBEC3A</span> Protein-coding gene in the species Homo sapiens

Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A, also known as APOBEC3A, or A3A is a gene of the APOBEC3 family found in humans, non-human primates, and some other mammals. It is a single-domain DNA cytidine deaminase with antiviral effects. While other members of the family such as APOBEC3G are believed to act by editing ssDNA by removing an amino group from cytosine in DNA, introducing a cytosine to uracil change which can ultimately lead to a cytosine to thymine mutation, one study suggests that APOBEC3A can inhibit parvoviruses by another mechanism. The cellular function of APOBEC3A is likely to be the destruction of foreign DNA through extensive deamination of cytosine.Stenglein MD, Burns MB, Li M, Lengyel J, Harris RS. "APOBEC3 proteins mediate the clearance of foreign DNA from human cells". Nature Structural & Molecular Biology. 17 (2): 222–9. doi:10.1038/nsmb.1744. PMC 2921484. PMID 20062055.

<span class="mw-page-title-main">APOBEC3B</span> Protein-coding gene in the species Homo sapiens

Probable DNA dC->dU-editing enzyme APOBEC-3B is a protein that in humans is encoded by the APOBEC3B gene.

<span class="mw-page-title-main">APOBEC3D</span> Protein-coding gene in the species Homo sapiens

Probable DNA dC->dU-editing enzyme APOBEC-3D is a protein that in humans is encoded by the APOBEC3D gene.

<span class="mw-page-title-main">ADARB2</span> Protein-coding gene in the species Homo sapiens

Double-stranded RNA-specific editase B2 is an enzyme that in humans is encoded by the ADARB2 gene.

<span class="mw-page-title-main">APOBEC</span> Enzyme involved in messenger RNA editing

APOBEC is a family of evolutionarily conserved cytidine deaminases.

<span class="mw-page-title-main">APOBEC3H</span> Protein-coding gene in the species Homo sapiens

DNA dC->dU-editing enzyme APOBEC-3H, also known as Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3H or APOBEC-related protein 10, is a protein that in humans is encoded by the APOBEC3H gene.

<span class="mw-page-title-main">APOBEC4</span> Protein-coding gene in the species Homo sapiens

C->U-editing enzyme APOBEC-4, also known as Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 4, is a protein that in humans is encoded by the APOBEC4 gene. It is primarily expressed in testis and found in mammals, chicken, but not fishes.

<span class="mw-page-title-main">Kataegis</span>

In molecular biology, kataegis describes a pattern of localized hypermutations identified in some cancer genomes, in which a large number of highly patterned basepair mutations occur in a small region of DNA. The mutational clusters are usually several hundred basepairs long, alternating between a long range of C→T substitutional pattern and a long range of G→A substitutional pattern. This suggests that kataegis is carried out on only one of the two template strands of DNA during replication. Compared to other cancer-related mutations, such as chromothripsis, kataegis is more commonly seen; it is not an accumulative process but likely happens during one cycle of replication.

<span class="mw-page-title-main">OyaGen</span>

OyaGen is a Rochester, New York-based startup company that is focused on developing treatments for HIV. The company was founded in 2003 by Harold Smith, a professor of biochemistry and biophysics at the University of Rochester. OyaGen was founded on research conducted by Smith and Hui Zang, an HIV researcher at Thomas Jefferson University.

<span class="mw-page-title-main">Nina Papavasiliou</span> Immunologist

Nina Papavasiliou is an immunologist and Helmholtz Professor in the Division of Immune Diversity at the German Cancer Research Center in Heidelberg, Germany. She is also an adjunct professor at the Rockefeller University, where she was previously associate professor and head of the Laboratory of Lymphocyte Biology. She is best known for her work in the fields of DNA and RNA editing.

Viviana Simon is a Professor of Microbiology at the Icahn School of Medicine at Mount Sinai (ISMMS). She is a member of the ISMMS Global Health and Emerging Pathogens Institute. Her research considers viral-host interactions and the mode of action of retroviral restriction factors. During the COVID-19 pandemic, Simon developed an antibody test that can determine immunity to Coronavirus disease 2019.

References

  1. ↑ Gail Dutton (1 October 2013). "HIV Researchers Seek a Potential Cure". Genetic Engineering & Biotechnology News. Retrieved 1 June 2014.
  2. ↑ David Miller; Mariel Selbovitz (February 2014). "The Deeper End of the Ocean: Host restrictive factors create research excitement". A&U: America's Aids Magazine. p. 52. Retrieved 1 June 2014.
  3. 1 2 3 4 5 "Dr. Harold C. Smith: A Life of Discovery". 11 March 2007. Retrieved 1 June 2014.[ self-published source ]
  4. 1 2 3 4 "Harold C. Smith, Ph.D." University of Rochester Medical Center. Retrieved 1 June 2014.
  5. 1 2 "RNA Editing". Gordon Research Conferences. Retrieved 1 June 2014.
  6. ↑ L Chan (22 May 1994). "Apolipoprotein B Messenger RNA editing: An Update". Departments of Cell Biology and Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Biochimie. 77 (195) (published 15 October 1994): 75–78. doi:10.1016/0300-9084(96)88107-7. PMID   7599279.
  7. 1 2 Smriti Jacob (19 July 2002). "Biotech researcher works to crack secrets of editing". Rochester Business Journal. Retrieved 1 June 2014.
  8. ↑ "Oyagen Inc. Corporate Summary". OyaGen. Retrieved 1 June 2014.
  9. ↑ Michael Wentzel (12 January 2004). "UR Invests in Anti-HIV Startup". Rochester Democrat & Chronicle. Retrieved 1 June 2014.
  10. 1 2 "Cannabis Science, Inc. Appoints Harold C. Smith, Ph.D., Professor in Biochemistry, Biophysics and Oncology and a Member of the Center for RNA Biology at the University of Rochester, School of Dentistry and Medicine, to Company's Scientific Advisory Board". Cannabis Science. 12 February 2013. Archived from the original on 1 May 2013. Retrieved 1 June 2014.
  11. ↑ Nishad Majmudar (1 September 2005). "OyaGen blazing path toward anti-AIDS drug". Rochester Democrat & Chronicle. Retrieved 1 June 2014.
  12. ↑ Harold C. Smith (February 2008). "RNA and DNA Editing: Molecular Mechanisms and Their Integration into Biological Systems". Wiley. Retrieved 1 June 2014.
  13. ↑ "University of Rochester Medical Center Receives $100,000 Grand Challenges Explorations Grant for Innovative Global Health". University of Rochester Medical Center. 22 October 2008. Retrieved 1 June 2014.
  14. ↑ Matthew Daneman (25 September 2010). "State pension fund invests in Henrietta biotech firm". Rochester Democrat & Chronicle. Retrieved 1 June 2014.
  15. ↑ "Scientific Advisory Board". IGXBio. Retrieved 1 June 2014.
  16. ↑ "American Health Council Names Dr. Harold Smith, Ph.D. to Education Board". GlobeNewswire News Room. Retrieved 2017-05-10.
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