Steven Sheriff was born in Washington, DC and moved with his family to Bethesda, Maryland just before his fifth birthday. His father was a lawyer and his mother was trained as a teacher. Sheriff was raised in a Jewish family and attended religious school, though his family was not observant. He was the oldest child and had three younger sisters.

In school, Sheriff enjoyed learning about a variety of subjects, including science, and the textbook Biological Science: Molecules to Man made an impression on him. Sheriff had a subscription to Science News Letter and once grew algae for a school science project. He was a lab assistant in biology in eleventh grade and chemistry in the twelfth grade. He was also a member of his high school’s bridge club and an alternate on the It’s Academic quiz bowl team.

Seeking a liberal arts education, and wanting to go to California, Sheriff decided to attend Pomona College. At Pomona, he took liberal arts and science courses, including coursework towards a major in chemistry/biochemistry. He was a student during the Vietnam War and remembers and participated in student protests on campus. Sheriff learned some computer programming in PL/I and had some exposure to Fortran. For his undergraduate thesis, he conducted research about solid-phase peptide synthesis. Outside of class, he participated in folk dancing and volleyball on campus. Sheriff spent summers during college in summer school, including in Pau, France, in Cambridge, Massachusetts at the Harvard Summer School, and in Davis, California at the University of California, Davis.

Sheriff applied to graduate programs and decided to accept an offer from the University of Washington. During his first summer there, Sheriff studied bacterial photosynthesis in the lab of William “Bill” W. Parson. The next summer, Sheriff worked in Jon R. Herriott’s (1937- ) lab, learning about protein crystallography. He started off conducting research about ribosomal proteins, but his advisor encouraged him to join work on the protein ferredoxin-NADP+ oxidoreductase. Sheriff introduced the lab to the use of isoelectric focusing as a technique. When he eventually got data, he converted it into an electron density map and also collected anomalous scattering data, leading to a published paper on his findings. Sheriff was a Teaching Assistant (TA) as a graduate student and he also trained an undergraduate student in the lab.

After his graduate studies, Sheriff accepted a postdoctoral position at the University of California, Los Angeles (UCLA) to pursue his interest in ribosomes. He was a National Institutes of Health (NIH) Postdoctoral Fellow working in the lab of James A. Lake (1941- ). Sheriff used biochemistry techniques to prepare samples for use with negative stain electron microscopy in his research on attempting to localize where elongation factor G bound to the ribosome. As an offshoot of preparing samples for electron microscopy, Sheriff and a fellow postdoc, Jerome Langer, were involved in research demonstrating that larger pore gels could be used in a centrifuge to separate large molecules from small molecules, including with ribosomes.

Sheriff eventually decided to continue his NIH postdoctoral fellowship in the lab of Wayne A. Hendrickson (1941- ) at the Naval Research Laboratory. Soon after moving to Washington, DC for the position, Sheriff met his wife. In Hendrickson’s lab, Sheriff worked on refining the structure of myohemerythrin. Anisotropic scaling and anomalous scattering were useful techniques in his research. Sheriff continued his work in Hendrickson’s lab through funding from the National Research Council. While at the Naval Research Laboratory, Sheriff used computer graphics equipment for the first time. Based on the success of accounting for anisotropic diffraction for myohemerythrin and other proteins undergoing refinement in the Hendrickson lab, he became an advocate for correcting for anisotropic diffraction.

Looking for a more permanent position, Sheriff accepted a role at Genex, where he knew most of the crystallographers in the company. There, Sheriff was charged with getting the diffractometer working, and he then used it to collect data. Sheriff also used the program Define Secondary Structure of Proteins (DSSP) to analyze the regular secondary structure of proteins.

After his work at Genex, Sheriff was hired as a consultant for Hendrickson, who had moved to Columbia University. Sheriff remained in Washington, DC and worked as a consultant from an office on the NIH campus. He attended meetings in David Davies’s lab and was eventually hired by David Davies (1927-2016) to work at the NIH.

At the NIH, Sheriff was based in the Laboratory of Molecular Biology in the National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases (NIADDK), which became the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). One of his projects was on the topic of diabetes in collaboration with Peter F. Kador in the National Eye Institute, though his overall work remained basic research using computational methods.

In the Davies lab, Sheriff worked on anti-lysozyme antibodies. He collaborated with Sandra J. Smith-Gill (1944- ), who mapped antibodies generated by immunizing mice with chicken egg lysozyme and ascertaining where they bound by using a panel of egg lysozymes from various bird species including bobwhite quail. Sheriff, Eduardo A. Padlan, who was a permanent staff member in David Davies’s lab, and a group at the Pasteur Institute led by Roberto Poljak (1932-2019) were each working on a different anti-lysozyme. Their findings allowed them to structurally define all three sites. Sheriff learned to use molecular replacement as a method for this project. Computational methods, including the program BRUTE, were helpful in getting the structure.

Eventually, Sheriff interviewed for a position at Squibb, which later merged with Bristol-Myers to become Bristol-Myers Squibb (BMS). Tasked with starting a protein crystallography group, Sheriff purchased equipment and hired staff. He served as a group leader at various points during his time at BMS, sometimes stepping back to take a break from the stress of the leadership role.

The group worked on a variety of projects over the years, including on thrombin, an anti-Lewis Y antibody, the protein MurB, the protein tyrosine phosphatase 1B, PTP γ (protein tyrosine phosphatase gamma), mannose-binding protein, cell surface receptor CD40, TGFβR-1 (transforming growth factor beta receptor one), polymerase HCV NS5B, and TNF-α (tumor necrosis factor-alpha). The work on mannose-binding protein and the anti-Lewis Y antibody were published in Nature Structural Biology articles. Sheriff also worked on factor XI, contributing to a drug that is in phase three trials and may make it to market. He worked on another drug, atazanavir, that made it to market and was in-licensed.

Sheriff discusses his approach to professional service, including serving on advisory and review panels and editing journal articles. He talks about the impact of the COVID-19 pandemic on his research and on the number of journal articles received for review. Sheriff reflects on changes over time in the kinds of drugs developed at BMS, stability in his crystallography group, and the use of patents in his work. He discusses the future use of crystallography in the pharmaceutical industry and changes in the industry. Sheriff reflects on the impact of his work. He shares his plans for retirement, including scientific involvement, spending time with family, and enjoying hobbies and traveling.

This interview was conducted remotely via Zoom.