A pioneer in understanding the biochemistry of male hormones and their receptors and how they influenced the development and progression of prostate cancer, Shutsung Liao, PhD’61, professor emeritus in the University of Chicago’s Ben May Department for Cancer Research, died at his Hyde Park home on July 20. He was 83 years old.
In 1968, Liao and colleagues discovered that in many androgen target tissues, the male hormone testosterone had no effect until it had been converted by the enzyme 5-alpha-reductase to dihydrotestosterone, which bound and activated its receptor. This shattered the dogma of that era that steroid hormones always bound to their receptors without prior alteration. This finding later led to the development of better drugs for androgen-dependent disorders such as benign prostatic hyperplasia and hormone-driven cancers.
“Shutsung Liao has been one of the truly central figures in the study of prostate cancer,” said Paul Talalay, the John Jacob Abel Distinguished Service Professor of Pharmacology and Director of the Laboratory for Molecular Sciences at Johns Hopkins School of Medicine. “His discovery that dihydrotestosterone was the most active androgen was a major contribution.”
“He was also a completely first-class, decent, principled, warm, human being,” Talalay added. “He had enormous respect for scholarship and for the academic process.”
When Liao asked University administrators to patent his groundbreaking discoveries involving the conversion from testosterone to dihydrotestosterone, they declined. At that time, for many universities, applying for patents was not standard practice.
One of Liao’s students, however, Tehming Liang, PhD’73, went to work at the pharmaceutical giant Merck & Co., where he helped develop a drug based on Liao’s research. The drug, called finasteride, blocks the activity of 5-alpha-reductase. Sales of finasteride—marketed as Proscar for benign prostate hyperplasia (BPH) and as Propecia for male pattern baldness—exceeded $1 billion in 2005. The success of Proscar helped change the University's approach to applying for patents based on its scientists’ work.
Liao also bridged the gap between research and development in the late 1980s and 1990s, when he worked closely with the University’s initial business-development group, known as ARCH. He connected them with financiers from his native Taiwan, who were looking for foreign investment opportunities. In 1998, he formed his own biotech company, Chicago-based Anagen Pharmaceuticals, Inc.
In 1988, after many others had tried, Liao’s team cloned and sequenced the human and rat androgen receptor cDNAs. This led to a better understanding of how androgens worked and the recognition that male hormones sometimes had little or no effect in men with a mutated androgen receptor gene, a life-changing genetic flaw.
In 1994, Liao’s laboratory discovered a new nuclear receptor. Since it could be found in almost all cell types, they named it Ubiquitous Receptor (UR). At the same time, a different laboratory found a close relative of UR, which they called the Liver-X Receptor, because it was abundant in liver tissue. Both receptors play important roles in lipid and cholesterol metabolism and are considered drug targets for treatment of cardiovascular diseases and other metabolic disorders. UR became known at LXRbeta.
Although he made a series of celebrated discoveries, Liao retained his “humble, mild manner,” said Geoffrey Greene, the Virginia and D. K. Ludwig Professor and chairman of the Ben May Department for Cancer Research. “He helped others become successful. He was very protective of his staff and students. He was quiet, thoughtful, self-effacing, a gentle person—except on the subject of Taiwanese politics. Then he became a real tiger.”
novel approach to therapy
Liao was born Jan. 1, 1931 in Tainan, Taiwan, which was, at that time, under Japanese rule. He grew up in Taichung during a turbulent period: World War II brought an end to Japanese rule in 1945. Subsequently, under the one-party rule of Chiang Kai-shek and the Kuomingtang Party, Taiwan was renamed the Republic of China and placed under martial law, also known as the White Terror, which lasted 38 years.
In 1956, after earning his bachelor and master of science degrees in agricultural chemistry from National Taiwan University, where he studied the life cycle of mushrooms, Liao came to the United States to study at the Illinois Institute of Technology. He was about to transfer to Cornell in 1957 when a chance encounter with Paul Talalay, then at the University of Chicago, lured him to a doctoral program at UChicagoy. He worked in Guy Williams-Ashman’s laboratory, which specialized in steroid hormones.
In 1957, Liao met Shuching Kuo, who was also studying at the University of Chicago. They married in 1960.
Liao completed his PhD in biochemistry at the University in 1961 and was asked by Charles Huggins, director of the University’s Ben May Institute for Cancer Research, to stay on as a research associate. (Huggins received the Nobel Prize for his work on prostate cancer in 1966.) Liao accepted. He rose quickly through the faculty ranks, becoming an assistant professor in 1964, associate professor in 1969 and a professor in 1972.
In addition to his work on male hormones, Liao was interested in applying Western scientific methods to the study of Chinese herbal medicines. He shared this interest with a successful Chinese businessman, Cyrus Tang, who in 2000 made a generous donation to create the Tang Center for Chinese Herbal Medicine Research, with Liao as its first director. Its mission, Liao said at the time, is “to put science into herbal medicine, to investigate the molecular actions of herbal medicines and to study novel approaches to therapies.”
Liao already had one such project underway. A compound found in green tea, called epigallocatechin gallate, or EGCG, was shown to inhibit the growth of certain tumors. In 1995 he and his senior research associate Richard Hiipakka, PhD’77, found that it was a potent inhibitor of 5-alpha-reductase, the enzyme that converts testosterone to dihydrotestosterone, which accelerates the growth of prostate tumors.
While studying the compound’s effects in the lab, Liao also began consuming 10 to 20 grams a day of dried tea leaves, the best dietary source of EGCG. “I'm the only human I can experiment on,” he explained. “I put it on salads, sandwiches and meats.”
For almost 50 years, Liao’s laboratory remained highly productive. He published more than 250 papers, many in prestigious journals. He and his colleagues were awarded 29 patents. He won several prestigious honors, including selection as a fellow of the American Association for the Advancement of Science and the National Academy in Taiwan.
'inspiration to many taiwanese people'
He was also an outspoken critic of Taiwan’s single-party government, the Kuomintang, and an advocate for efforts to bring democracy and human rights to Taiwan. Despite being blacklisted, he would regularly visit Taiwan to meet with other dissidents, oversee elections, give speeches and galvanize support for Taiwan’s independence, sometimes at considerable personal risk.
“It wasn’t until later in life,” said his daughter, May, “that we truly understood the risks that he took to speak out for his beloved country. His passion for and dedication to Taiwan’s independence was an inspiration to many Taiwanese people.”
With a strong belief in community and giving back to one's homeland, Liao founded the North American Taiwanese Professor's Association in 1980. NATPA provided professors and scholars a forum for sharing ideas, exchanging scientific knowledge and research, strengthening cultural ties between the North America and Taiwan and working for the general welfare of Taiwanese communities. NATPA strengthened support and awareness surrounding issues related to Taiwan's move toward democracy and prosperity.
Liao's research and teaching philosophy was deeply influenced by his father, Chi Chun Liao, a highly respected Taiwanese painter and professor. Like his father, Liao never sought competition and invited his students to think independently. “I never advocate reading books every day in the library,” he said, “but encourage students to spare their mind to think, to find and to create."
His colleagues describe him as calm, patient, frugal, respectful and relentlessly polite. Simple mottos, rather than regulations, directed life in his office and lab. “Be creative, not competitive,” he told students and staff. A research project need not be fashionable “as long as it’s new, and as long as it’s true.” And when writing a paper, a grant proposal, or just a memo, authors should aspire to “a poem, not a dictionary.”
Liao is survived by his wife, Shuching; four daughters, Jane, Tzufen, Tzuming and May (Matthieu Schmitter); and two granddaughters, Leila and Cailin. Funeral services were private. A memorial service is being planned for mid-October.