William Weis, a pioneer of molecular imaging, dies at 64

William “Bill” Weis, PhD, known for elucidating the three-dimensional structures of a variety of molecules and for developing advanced X-ray crystallography methods, died of brain cancer on Oct. 13 in his Palo Alto home. He was 64.

Before he took medical leave for glioblastoma, Weis was chair of the structural biology department. He was also a professor of molecular and cellular physiology and of photon science and was the William M. Hume Professor in the School of Medicine. He worked at Stanford Medicine for 30 years.

“The department of structural biology’s longstanding preeminence owes greatly to Bill’s extraordinary contributions as a scientist and mentor,” said Lloyd Minor, MD, dean of the Stanford School of Medicine. “He encouraged and enlightened other scientists even far outside his own field. He truly was a bright and guiding light, illuminating his own and others’ research at Stanford Medicine.”

Weis described the structure of many proteins, including a group called catenins, which bind cells together and build tissue. His research also focused on cell-cell communication and the internal and external organization of cells. The imaging techniques he developed include advanced X-ray crystallography methods, which enhance the resolution of three-dimensional structures of proteins. These structures help scientists determine how the proteins interact with surrounding molecules and which molecules are good possibilities for drugs.

“Bill was an incredible force at Stanford Medicine and pushed forward the latest and greatest technologies to image protein structures, applying forefront methods from physics to understand biology,” said Ted Jardetzky, PhD, a professor of structural biology and the department’s current chair.

Early life

Weis was born June 10, 1959, in Queens, New York, where he grew up in a middle-class family, according to an interview with Helene Cohen at Stanford University in 2000. He graduated with a bachelor’s in biochemical sciences in 1981 from Princeton University. In 1988 he earned his PhD at Harvard University, where he worked on influenza hemagglutinin, a surface protein responsible for binding the flu virus to host cells.

He completed two postdoctoral fellowships: At Yale University, he enhanced and refined three-dimensional structures of influenza virus hemagglutinin. At Columbia University Medical Center, he studied protein-carbohydrate interactions, a molecular detail that largely determines how cells stick together.

Weis accepted a position as an assistant professor of structural biology at Stanford Medicine in 1993. He was promoted to associate professor in 1999 and became a full professor of structural biology, of molecular and cellular physiology, and of photon science in 2004. He was the director of the graduate program in biophysics from 1999 to 2008, then chaired the department of photon science from 2013 to 2016 and the department of structural biology from 2014 to 2022, when he took a sabbatical after his glioblastoma diagnosis.

Weis was elected to the U.S. National Academy of Sciences in 2019 and received many teaching honors, including Stanford Medicine’s Outstanding Instruction in Preclinical Teaching Award five times. He was a member of the Sigma Xi, American Society for Cell Biology, the Biophysical Society and the American Crystallographic Association, among other organizations. He served on several editorial boards including those of the Journal of Structural Biology and eLife.

A generous nature

Although Weis was one of the best X-ray crystallographers in the world, said Brian Kobilka, MD, a professor of molecular and cellular physiology, he wasn’t too proud to help inexperienced junior colleagues with their endeavors.

When Kobilka arrived at Stanford Medicine in 1990 as an assistant professor, he wanted to reveal the structures of proteins called G-protein-coupled receptors, which are proteins on the cell membrane that bind hormones and neurotransmitters and trigger physiological effects. This family of receptors are targets for approximately 30% of drugs used in the clinic. With Weis’s help, Kobilka was able to determine the shapes of these G-protein-coupled receptors.

“Bill played an essential role in these studies that led to me to be awarded a Nobel Prize in chemistry,” said Kobilka, the Hélène Irwin Fagan Chair in Cardiology. “Bill knew much more about my primary focus than I knew about his primary focus. That’s just the kind of person he was; he was really engaged in science beyond his own research.”

Weis loved figuring out how things worked, his colleagues said. The Wnt signaling pathway, Kobilka said, was a great example of that. Weis elucidated the structural features of the pathway, which helps regulate renewal of tissue. When dysregulated, Wnt signaling drives many cancers. It’s one of the more complicated signaling pathways in the human body, Kobilka said.

Understanding fundamental concepts and helping others excited Weis the most, Jardetzky said. “Bill was always someone I turned to for advice and insight. He was a person who enjoyed all advances in science and was supportive of other people’s work just as much as his own.”

“Bill was an all-around mensch,” said Georgios Skiniotis, PhD, a professor of molecular and cellular physiology, of structural biology, and of photon science. “He was a genuinely good person who devoted his energy to whom or what needed it the most, and he deeply cared about the community and its progress as a whole.”

In 2015, Weis and Axel Brunger, PhD, professor of molecular and cellular physiology, of neurology and of photon science, were among a group of faculty and Stanford Medicine leaders who spearheaded the Stanford Cryo-Electron Microscopy Center and Stanford-SLAC Cryo-Electron Microscopy Facilities to capture high-resolution images of cells through cryogenic electron microscopy, a technique that visualizes flash-frozen samples under extremely low temperatures. Brunger said that working and collaborating with Weis on the center is one of his fondest memories.

“Bill made major contributions in basic cell science,” Brunger said. “He had a great interest in applying the latest technologies to interesting biological problems and actually made it possible by making the methods accessible for other scientists.”

Travel and leisure

Although Weis spent most of his time in the lab, he made time for himself and others outside of Stanford Medicine. Weis met his future wife, Sherin Halfon, a biotechnology scientist, in 1995, and they married in 2017.

“Bill was dedicated to science and to others,” Halfon said, noting that he attended one of his student’s qualifying exams during his last week in hospice.

Weis valued spending time with his wide circle of friends, was an avid swimmer and chef, and enjoyed renovating his mid-century home in Palo Alto with his pit bull rescue, Kermit, at his side. When he wasn’t at home, he enjoyed dining at fine restaurants or traveling with Halfon, often before and after conferences.

Weis is survived by Halfon and two older brothers, Philip and Richard Weis.  

Bill supported several nature and social justice charities, including the Nature Conservancy and the Southern Poverty Law Center, and donations in his name may be made to these organizations.