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. 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. 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. He received more than $8 million in total funding over the following 12 years from the
National Institutes of Health (NIH) and other agencies. OyaGen is a biopharmaceutical company which develops therapies to fight viral illness through editing enzymes, with a focus on Human Immunodeficiency Virus (HIV). 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. 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. 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. The New York State Common Retirement Fund invested in OyaGen in 2006 and again in 2010. In February 2013, Cannabis Science, Inc. added Smith to its scientific advisory board. 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. He continues as a professor at the University of Rochester, School of Medicine and Dentistry, teaching biochemistry and biophysics. 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==