Moving Toward Firsts, Research, and Impact

Although a chemist by training, Robert Guenette has followed a simple physics principle throughout his life: forward momentum. While he has not always known what he is moving toward, he always keeps going, pushing through any obstacles to chart new paths. “That sense of progressing and like feeling like you’re going somewhere,” he says, has been central to his success.

While a 2008 Amgen Scholar — in the first summer of the Program — Guenette had no plans to work at Amgen one day, or even to work in the biotech industry, but he knew he was moving toward a research career. And that forward momentum would propel him to grad school and then eventually to a postdoctoral fellowship at Amgen, where he is now a senior scientist working on target protein degradation as a silencing mechanism in drug discovery.

Guenette says he is not surprised he ended up in industry but he was surprised to find himself leaving the Midwest and moving to the West Coast after growing up and getting his education in Wisconsin. At the 2024 Amgen Scholars North American symposium at UCLA, Guenette shared how he navigated his career and had the opportunity to connect with current Scholars and other alumni who are now facing uncertainties within their own paths. 

In his own self-reflection on his career, Guenette has identified two clear themes. One theme is about what it has been like for him to live through a series of “firsts.” In addition to being in the first cohort of Amgen scholars, Guenette was the first in his family to attend college and did his PhD with a brand new professor — giving him unique insights into what it’s like to be a first-time PI. In each of these events, Guenette found useful milestones, “a sense of newness that I have always appreciated,” he says. “These are personal milestones that may not end up on a CV or in an award, but pioneering those things for yourself is an incredible opportunity.”

Participating in Amgen Scholars while in college was a logical step for Guenette who had always been interested in science and whose interests intensified when he reached high school. “It was an instant love affair,” he remembers.”There’s magic in science. Even just mixing clear solutions with other clear solutions in the lab environment, you’re discovering the world.”

Guenette attended a small liberal arts college in his home state Wisconsin, Lawrence University, where he enjoyed the smaller classes and the opportunity to pair chemistry with classes in the arts. His Amgen Scholars summer at the University of Washington gave him the valuable experience of doing research in a bigger university and solidified his desire to pursue grad school. He would go on to get a PhD at the University of Wisconsin-Madison. 

“Amgen Scholars was my first formal research experience in a large lab,” he says. “And it crystallized that I could do research.” It also helped spur his decision to switch from analytical chemistry to organic chemistry with a focus on chemical biology. 

This leads to the second big theme for Guenette’s reflection on his path: “position yourself as proximal to what you want to do as possible,” he says. “If you want to see what biotech is like, go on and live it; get that experience.” 

When Gunette was in grad school, he knew he was interested in a potential industry path. He saw industry as a way to continue in research but with more work-life balance and with the potential for greater impact. So, he helped to position himself as part of a biotechnology training program fellowship grant. That program helped give him resources and tools to learn about and then look for positions in industry after completing his PhD. This was at a time when many companies were just starting to establish more formal postdoc programs. The post he took at Amgen in oncology was a great fit for his work in target protein degradation, which uses ubiquitin biology that he had been studying.

The postdoctoral work led to his current position at Amgen, where Guenette has been for five years, working to identify E3 ligases that will induce degradation of key targets in cells. He likens it to a silencing technique like that of CRISPR but at the protein level rather than the genetic level. “Rather than knocking out a gene to have an effect on a disease state, we’re targeting proteins to degrade them,” he explains. 

Much of the work is on cardiometabolic disorders but the technique has broad applications for drug discovery in different therapeutic areas. Guenette spends most of his time in the lab but also in meetings with collaborators, from other scientists to physicians.

Whether he is talking to Amgen Scholars or to his nieces and nephews, Guenette loves to explain his work to others, through simple questions that can help establish a baseline. “It’s been an interesting transition from being educated to now educating other people on what your day-to-day looks like,” he says. “For me, it’s always been a story of movement, taking my research skills and moving toward cancer biology and then moving to drug discovery.”