"Many times in science, you start out looking for “A,” but you end up finding “X.”
That’s the advice Dr. Jeffery Kelly gave to a young biochemistry student during his Homecoming Weekend visit to campus this past fall. He said this not only because it’s what he’s personally experienced throughout his career – it’s how he found himself in that career in the first place.
Jeff Kelly came to SUNY Fredonia as an aspiring engineer from his home town of Medina, N.Y., in the fall of 1978, intending to be a part of a “3-2 program” that would afford him three years at SUNY Fredonia and another two at a partner institution. Like many students, however, his plans changed after he gained some new experiences and was influenced by some key faculty along the way.
“I wound up working with [Chemistry] Professor Tom Harris,” Dr. Kelly recalls, “and I began to realize that my research was really what I was drawn to, where I was developing a passion.”
The word “passion” is an understatement – if that’s possible – for this Class of 1982 alumnus whose career reached a new high in recent years. Kelly led a team in the discovery of a drug that cures a rare amyloid disease, within a class of diseases that includes Alzheimer’s. The drug is so full of potential that, in 2010, pharmaceutical giant Pfizer acquired FoldRx, the company Kelly co-founded. This new drug, Tafamidis, is the culmination of a series of investigations that began in 1987, when Kelly was a postdoctoral fellow at The Rockefeller University. It is the result of decades of observations, trials and errors, frustrations and jubilations.
And for the 8,000 individuals worldwide who are afflicted with Transthyretin Amyloidosis (TTR), an organ-debilitating disease that eventually proves fatal, it is the miracle they have been waiting for, and a second chance at life.
Clearly, Kelly’s path has seen many turns as he’s gone from a young Western New Yorker hoping to find his calling to the Vice President of Academic Affairs and Dean of Graduate Studies of the Kellogg School of Science and Technology at The Scripps Research Institute in La Jolla, Calif. His journey, however, has been as satisfying for him as the actual results he’s produced along the way.
“That’s been a theme of my life. That’s come up again and again,” Kelly agrees. “I think it’s one of the most amazing things about science. If you are really good at making observations, you can often turn lemons into lemonade.”
The “lemons” in Jeff’s case was a general interest in how beta sheet proteins fold. As he was reading some literature, he came across transthyretin, a protein which caused a mysterious disease, and he realized that the studies he was involved in had revealed an idea about how this disease might occur. He later would “accidentally observe,” while pursuing a different series of experiments, that in order for the proteins to aggregate (cause the disease), they would have to surmount a very high activation barrier.
“We realized there was a small molecule binding site that wasn’t utilized, and so we took advantage of that and made a drug (Tafamidis) that increases the activation barrier,” Kelly says. “We made a series of observations that took us light years beyond what we originally envisioned the answer would be.”Best of all, this discovery has the potential to be the proverbial tip of the iceberg, due to the similarities between TTR and many other more prevalent neurodegenerative diseases, which means this research could possibly benefit the lives of millions.
“We’re really passionate about trying to understand diseases like Alzheimer’s, Parkinson’s and Huntington’s,” Kelly says,“but in order to accomplish that, we have to understand more about those diseases, so our research has both a biological and a chemical component.”
Jeff and his team are now focused on developing a few small-molecule drugs which activate specific pathways that protect against many neurodegenerative diseases, and they’re starting by looking at the mechanisms that protect people while they’re young.
“The biggest risk factor for these diseases is aging,” Kelly explains. “We now know something about the genetics of aging and the pathways that change. There is reason to believe that we can not only make people live longer, but make their so-called health span longer as well, so that people could live to, say, 95 without developing dementia.”
This new approach represents somewhat of a shift in the scientific approach he and his colleagues at Scripps and FoldRx have taken historically. “Heretofore, we’ve made small molecules that target a specific protein and prevent their aggregation,” he adds. “There are over 100 proteins whose aggregation leads to neurodegeneration, and I don’t have enough time left in my life to go after all of those. So we’re taking a more generic strategy. It’s a bit of a gamble, but I think it’s going to work.”
Despite his demanding career – and that he now lives on the opposite side of the country – Jeff has maintained a very strong bond with his alma mater. He comes back regularly to speak with students, visit with faculty, and assist in the growth of the campus. He has been a member of the board of the Fredonia College Foundation since 2008. More recently he was named to the Natural Sciences Advisory Council, a select group of alumni who are providing valuable insights in the planning and design of SUNY Fredonia’s new Science Center, set to break ground in May.
“Fundamentally, I enjoy it. I enjoy being here,” Jeff admits. “I guess it’s also a sense of obligation. A couple of people here made a huge difference in my life and enabled my career – and I would say enabled the discovery of Tafamidis and the training of almost 100 graduate students now. So I guess if I can impart a little bit of wisdom on aspiring students and motivate them to do things they might not think about, then maybe that will do some good.”
The two people Kelly credits are Dr. Philip Kumler, whom Jeff says taught him organic chemistry “in such a way as to make it really interesting,” and Dr. Harris, his undergraduate research advisor, who helped Kelly understand the practical aspects of science observation and the exciting parts about discovery.
But Jeff is imparting more than just wisdom to his alma mater. In addition to providing guidance for the new $60 million Science Center, he’s given the college a substantial financial gift as well.
His generosity will help the Department of Chemistry and Biochemistry fund new scholarships and equipment to complement the state-of-the-art facility set to open in two years.
“My motivation for making a gift to Fredonia was two-fold: to honor my family, who made my education possible, and to provide a yearly scholarship for a chemistry or biology student who is passionate about making the world a better place to live in the future,” he said.
Upon reflection, Kelly has seen just how perfect a fit Fredonia was for him to launch his career. Although he went on to earn his doctoral degree at the University of North Carolina, and was a faculty member at Texas A&M University – institutions much larger than Fredonia – he believes the smaller size and more personal approach he found in Houghton Hall was the difference maker in his life.
“For me, it was invaluable that I started learning about science here,” he says. “There are a lot more one-on-one interactions. I didn’t have a particularly strong training in science as a high school student, so I had a lot of catching up to do. The dedication of the faculty here enabled me to [learn more].”
He also recognizes that Fredonia is special, in terms of the significant research opportunities for undergraduates; at many schools, those are reserved for graduate students.
“Fredonia…gives you the opportunity to work with people in their labs, trying to solve real problems,” he explains. “That’s how you ultimately learn real science, by innovating and being creative and understanding that what you were taught yesterday isn’t really true. It’s mostly true, but science is never absolute. I thought Fredonia was particularly good at that, preparing you to solve real-world problems as opposed to an education that is largely philosophical.”
Fredonia also instilled in Kelly how important teaching is to science research, a tenet which some larger research institutions don’t always follow. “I view teaching and research as inextricably linked,” Kelly advises. “If you’re going to have a robust and scholarly research activity, you have to take teaching seriously. You need to know the background material to realize that, if your experiment doesn’t go as intended, you may have actually discovered something far more interesting than what you had envisioned.”
Despite the demanding lifestyle he has chosen, Kelly is quick to point out the importance of achieving balance in one’s life. He tells students that they can be serious scientists and still have time for outside activities and family.
“People who are good at time management can have it all,” he assures. “People who aren’t so good at it…their vocation tends to dominate their life. I personally like to have a little diversity in my life, so I try to get better at it all the time.”
And what does he do with his free time? Don’t let the white lab coat fool you. “I enjoy racing Porsches,” he admits with a grin. “It’s completely the opposite of what I do every day.”
Then again, in the race to find treatments for devastating neurodegenerative diseases, a little speed is surely an asset.
