Fighting the good fight

Paul Goodfellow works to identify the genetic changes that lead to cancer

Paul J. Goodfellow, Ph.D., is in a professional war with cancer. The professor of genetics, surgery, and of obstetrics and gynecology brings an arsenal of knowledge and passion to his research battle with the formidable adversary.

“Disease is competition. In the case of cancer, it’s like Darwinian evolution: The best genetic material wins,” Goodfellow says. “With cancer, it’s a cat-and-mouse game. The cancer cell needs to change its genetic makeup to outsmart the host.”

Paul Goodfellow (right), and Israel Zighelbolm, clinical fellow in OB/GYN oncology, evaluate gels to identify mutations in a DNA repari gene in endometrial cancer specimens.
Paul Goodfellow (right), and Israel Zighelbolm, clinical fellow in OB/GYN oncology, evaluate gels to identify mutations in a DNA repari gene in endometrial cancer specimens.

Using what he calls “clinical specimens,” Goodfellow looks at inherited factors contributing to cancer risk. Through his research in the Cancer Genetics Program at the Siteman Cancer Center, Goodfellow works to identify the genetic changes that lead to cancer, particularly endometrial, or uterine, cancer. By better understanding the genetic causes of the disease, he hopes to halt its progression through screening, early detection and intervention.

Endometrial cancer is the most common cancer of the female reproductive organs, according to the American Cancer Society. There were an estimated 40,880 new cases diagnosed in the United States last year, making it the fourth most common cancer in women. Although 7,310 women died from the disease in 2005, Goodfellow says there are more survivors of endometrial cancer than any other gynecologic cancers.

Goodfellow’s work is a manifestation of his dedication to health.

“I believe in the importance of translating research findings to improved patient care,” he says.

David G. Mutch, M.D., the Ira C. and Judith Gall Professor of Obstetrics and Gynecology, collaborates with Goodfellow on endometrial cancer research. Mutch says Goodfellow is aptly named.

“He’s a great friend and collaborator,” Mutch says. “Paul is the ultimate team player. Paul spends more time helping others than helping himself. He is dedicated to teaching and helping others.”

It’s in the genes

Born near Kingston, Ontario, Goodfellow traces his interest in biology and botany to his childhood in rural Canada. He attended a one-room schoolhouse, and frequently he’d walk through fields to get there. Those walks sparked observation of and appreciation for nature.

After earning an undergraduate degree in biology from Queens University in Ontario in 1978, he came to the United States for a master’s degree in plant pathology at the University of Tennessee.

(From left) Paul Goodfellow, his wife, Carol Stewart, and sons Jonathan and Jamie are all outdoor enthusiasts who like to spend summers in eastern Ontario.
(From left) Paul Goodfellow, his wife, Carol Stewart, and sons Jonathan and Jamie are all outdoor enthusiasts who like to spend summers in eastern Ontario.

His early academic work involved agricultural genetics. He considered studying the effect rootworms have on different strains of tobacco. But the purpose of the research by tobacco companies is to be able to plant the most resistant strain of tobacco, something Goodfellow felt was “dirty.”

That led to his work in human genetics and a Ph.D. in biology/pediatrics from Queens University in 1985, a time when genetic research was blossoming.

The path was a good one for Goodfellow, whose excitement about his research is evident as he moves to the edge of his chair and gestures with animated enthusiasm to describe it.

“Genes are the root cause of cancer, and genetic research holds the promise of getting to what’s going wrong,” he says.

Specifically, he strives to understand how DNA replication fails in the cancer cell and what that means in terms of genetic decline.

DNA replication is a complex process. Each cell has 3 billion base pairs of DNA that must be copied with every cell division.

“With a genome of 3 billion base pairs, a lot can go wrong,” Goodfellow says. “Along the way, there can be mistakes.”

Under normal circumstances, each base pair match is checked, and any mismatches are repaired by enzymes. But if cells lose their ability to repair DNA mismatches, that can lead to genetic mutations. Such genetic damage can cause cells to grow where they shouldn’t, resulting in cancerous tumors.

“Genetic damage occurs over time,” Goodfellow says. “It’s wear-and-tear on genetic material that leads to cancer. We live a long time, and as we age the machine begins to break down. Once you lose genetic repair in long-lived cells that normally repopulate tissues, you are on a slippery slope. The ability to acquire lots of genetic damage allows a tumor cell to compete in a body.”

Goodfellow’s research involves comparing healthy cells with cancerous tumors. Using a library of more than 700 tumors, Goodfellow sometimes compares them to cancer-free cells from 750 healthy subjects older than 65 (his goal for the project is 2,000 healthy men and women). As the tumors carry the mutations, comparison with healthy cells could be the key to recognizing where and how the damage occurred.

Paul J. Goodfellow

Title: Professor of genetics, surgery and of obstetrics and gynecology

Family: Wife, Carol Stewart, an artist; two sons, Jamie and Jonathan.

Goodfellow collaborates with his wife on art projects, including collages on display in the Farrell Learning and Teaching Center. The works, which are representations of his medical research, contain DNA gel analyses and colorized images of actual tumors.

Those findings will help identify the inherited factors that lead to the shut down of DNA repair, allowing women and their family members to learn who is at risk and seek earlier cancer screening and detection.

Already, Goodfellow’s research has contributed to medical knowledge, Mutch says.

“I feel very lucky to have shared a collaboration with him over the past 12 years,” Mutch says. ” We have published more than 40 papers together, and during this time, he has identified many genetic abnormalities that have led to a better understanding of the genesis of endometrial cancer.”

Alison J. Whelan, M.D., associate dean for medical student education, agrees. She has worked with Goodfellow as co-director of the Hereditary Cancer Registry Core at Siteman.

“Paul Goodfellow is the quintessential academic scientist,” she says. “He is a critical thinker with a great curiosity and attention to detail that together lead to first-rate research.”

His best genetic work

Goodfellow is as dedicated to family as he is to his work. It is his personal life that he says is “the best genetic work I’ve done.” By that, he means his two sons, Jamie, a freshman majoring in economics and history at Queens University, and Jonathan, a sophomore at Clayton High School.

In Goodfellow’s office hang two oil paintings by his wife, artist Carol Stewart, and photographs of his family on vacation. As outdoor enthusiasts, the family spends summers in what Goodfellow calls “cottage country” in eastern Ontario. Both boys are avid lacrosse players — the national sport of Canada.

“Our children are both of the Canadian lifestyle,” Goodfellow says.

Along with medical-research collaboration, Goodfellow collaborates with his wife on art projects, including collages on display in the Farrell Learning and Teaching Center. Representations of his medical research, the works contain DNA gel analyses and colorized images of actual tumors.

Goodfellow, who joined the School of Medicine in 1992, said he enjoys the St. Louis area.

“St. Louis has been a wonderful home academically and for our family,” says the Clayton resident.

Previously, he had spent four years as an assistant professor in the Department of Medical Genetics at the University of British Columbia and three years at the Imperial Cancer Research Fund in London as a postdoctoral fellow and visiting research fellow.

Through the years, he has co-authored 126 journal articles, 13 reviews and book chapters and 92 abstracts. He also has received numerous awards, including the 2003 Washington University School of Medicine Academic Women’s Network Mentor Award. “It was an honor to receive that as a recognition of contributing to the career advancement of women,” Goodfellow says.

Passing the torch

Teaching and assisting others in their careers are areas in which Goodfellow shines.

“Paul is a standout as a role model for academic medicine,” Whelan says. “He is a terrific collaborator and a wonderful teacher and mentor to students, postdocs and young faculty members. His willingness to invest time, energy, enthusiasm and intellect in support of others’ research is truly remarkable.”

Such investment pays off in personal satisfaction.

“Knowledge sharing is really important to me,” Goodfellow says. “I am part of a team.”

That team includes not only Goodfellow’s colleagues — with whom he enjoys sparring intellectually in review panels — but also the students, other trainees and staff who work in his lab. Among his greatest rewards, he says, is knowing that he helped someone as they progress in academic medicine.”

Like genetic copying, Goodfellow passes his knowledge to future generations who will keep up the good fight.

“The one thing we aspire to,” he says, “is to replace ourselves with better people who will make a difference.”