Chemistry Nobel Prize winner Carolyn Bertozzi had a hand in early stem cell research

Carolyn Bertozzi. Image credit: Andrew Brodhead

The 2022 Nobel Prize in Chemistry has been awarded to Carolyn R. Bertozzi of Stanford University, Morten Meldal of the University of Copenhagen, and K. Barry Sharpless of Scripps Research. The three scientists are recognized for their independent development and contributions to the field known as click chemistry and bioorthogonal chemistry. 

Sharpless and Meldal are credited with laying the foundation for click chemistry, a functional form of chemistry in which molecular building blocks snap together quickly and efficiently. But it’s Bertozzi—a Stanford professor, chemist, mentor and early CIRM grantee—who is being recognized for taking click chemistry to a new dimension and utilizing it in living organisms.

A press release from The Royal Swedish Academy of Sciences describes Bertozzi’s accomplishments as follows:  

“To map important but elusive biomolecules on the surface of cells – glycans – Bertozzi developed click reactions that work inside living organisms. Her bioorthogonal reactions take place without disrupting the normal chemistry of the cell.  

These reactions are now used globally to explore cells and track biological processes. Using bioorthogonal reactions, researchers have improved the targeting of cancer pharmaceuticals, which are now being tested in clinical trials.” 

Click chemistry and bioorthogonal reactions, the press release notes, have taken chemistry into the era of functionalism and brings the greatest benefit to humankind. 

Bertozzi celebrates her Nobel Prize win. Image courtesy Kurt Hickman and Harry Gregory for Stanford.

A Hand in Early Stem Cell Research 

Bertozzi also had a hand in early stem cell research funded by the California Institute for Regenerative Medicine (CIRM), California’s stem cell agency.  

As a recipient of a SEED Grant from the agency in 2007, Bertozzi helped jump-start human embryonic stem cell (hESC) research in California. Through that funding, Bertozzi’s lab at UC Berkeley studied the roles of cell surface sugars in the transformation of hESCs into cell types useful for the treatment of human diseases.  

“This work will contribute to a better understanding of how stem cells interact with other cells in their environment and how they mature into different cell types,” Bertozzi said. 

A Prolific Mentor

Bertozzi is also recognized as a prolific mentor, having advised more than 250 undergraduates, graduate students, and postdoctoral fellows, including CIRM Bridges alumni Ian Blong, whose experience working in Bertozzi’s lab was profiled in The Stem Cellar.  

Bertozzi founded and continues to lead the Sarafan ChEM-H Chemistry-Biology Interface Predoctoral Training Program, which helps train graduate students to bridge the gap between chemistry, biology, and medical research.  

She also helped launched a program to prepare recent college graduates from diverse and historically underrepresented backgrounds to apply for doctorate programs in the sciences. In 2022, Bertozzi was recognized with a Lifetime Mentor Award from the American Association for the Advancement of Science for her commitment to mentorship and increasing diversity in science.

CIRM congratulates Bertozzi, Meldal and Sharpless on their Nobel Prize award and for their impressive accomplishments. Read an in-depth profile of Bertozzi and her work on the Stanford Magazine website. Read more about all three scientists and their work here. Read the news release from Stanford here.

CIRM Bridges program prepared student for research of a rare disease

Ian Blong, Ph.D., CIRM San Francisco State University Bridges to Stem Cell Research Alumnus

Recently, The New York Times released a powerful article that tells the stories of four different families navigating the challenges of having a family member with a rare disease. One of these stories focused on Matt Wilsey, a tech entrepreneur and investor in California’s Silicon Valley, and his daughter Grace, who was born with an extremely rare genetic disorder named NGLY1 deficiency. This genetic disorder causes developmental delay, intellectual disability, seizures, and other movement issues.

Matt and Kristen Wilsey with their 10-year-old daughter Grace, who has a rare genetic disorder, at the Grace Science headquarters in Menlo Park, Calif.
Image Credit: James Tensuan for The New York Times

Matt decided to put his entrepreneurial and networking skills to good use in order to form Grace Science Foundation, an organization whose focus is to pioneer approaches to scientific discovery in order to develop a cure for NGLY1 deficiency. One researcher that Matt brought on board was Carolyn Bertozzi, Ph.D., a chemist from Stanford University. A graduate student in her laboratory, Ian Blong, Ph.D., decided to study NGLY1 and was able to complete his dissertation while working on this topic at Stanford University.

Ian’s journey towards obtaining his Ph.D. started after being accepted into the San Francisco State University (SFSU) CIRM Bridges to Stem Cell Research Master’s Program. CIRM funding for this program allowed students like Ian to take courses at SFSU while also working in labs at world renown institutions in the Bay Area such as UCSF, Stanford, and UC Berkeley.

Carolyn Bertozzi, Ph.D.
Image Credit: L.A. Cicero

In exploring the various options afforded to him by the CIRM, Ian found Dr. Bertozzi’s lab at UC Berkeley, where he focused on early stage discovery research. His master’s thesis project focused on how to generate rare neuronal and and neural crest cells from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). Both of these stem cell types can generate virtually any kind of cell, but iPSCs are unique in that they can be generated from the adult cells (such as skin) of a patient.

Ian decided to continue his studies in Dr. Bertozzi’s lab by continuing his research in a Ph.D. program at UC Berkeley. He credits the SFSU CIRM Bridges Program with giving him the opportunity to work under a prestigious PI and in her lab at UC Berkeley, which allowed him to continue his studies there.

“The CIRM Bridges Program gave me the confidence and resources to pursue my dreams. Being able to have the capability of going to Berkeley and do research with top tier scientists along with the support from CIRM. Without CIRM, I wouldn’t have had the courage to go to those universities to get my foot in the door.”

Eventually, Dr. Bertozzi move her operations to Stanford University and Ian continued his Ph.D. studies there. Stanford provided him the opportunity to focus more on the translational stage, which is an area of research aimed at developing a therapeutic candidate. Going into his Ph.D. work, Ian was able to build upon his previous “discovery stage” knowledge of generating neuronal and neural crest cells from iPSCS and hESCs.

An area of his work at Stanford focused on generating neural crest cells from iPSCs of those with NGLY1 deficiency. The goal was to identify a phenotype, which is an observable characteristic such as physical form. Identifying this would help better understand potential differentiation pathways that underlie NGLY1 deficiency, which could lead to the development a potential treatment for the condition.

Flash forward to present day and Ian is still using the knowledge he learned from his time in the SFSU CIRM Bridges to Stem Cell Research Program. He is currently a scientist at the healthcare company Roche, where his focus is on manufacturing future diagnostics and therapeutics on a much larger scale, a complex and extremely critical process necessary in widely distributing potential stem cell-based treatments.

Ian’s experience and opportunities provided to him is just one of the many examples of how the various CIRM Bridges Programs across California have given students the resources needed to become the next generation of scientists.