O'Malley's Legacy Grew from Fowl Beginnings

The luck of the Irish coupled with an enduring dedication to education and research has earned Bert O'Malley, M.D., a place in history in the field of molecular endocrinology.

The fascination of Bert O'Malley, M.D., with steroid hormones and their effects on the cell nucleus, genes and the level of gene expression began with a theory and chickens-—many chickens.

In an essay published in 1991 in the journal Endocrinology, Peter O. Kohler, M.D., President Emeritus of Oregon Health and Science University, remembered O'Malley and the chickens from their days together in the late 1960s at the National Institutes of Health.

"One of my strongest memories is of Bert O'Malley's chicken studies... In order to carry out the experiments, large numbers of chicks had to be injected every six hours around the clock for six successive days. Bert dutifully came in every six hours to make the evening, night and holiday injections. I always believed Bert deserved every accolade after watching him try to reach recalcitrant chickens hiding in the far corners of a side-entry cage in the wee hours of the morning....Those were the halcyon days."

Those halcyon days resulted in one of O'Malley's seminal discoveries-—the one most of his colleagues credit with initiating the whole field of molecular endocrinology.

O'Malley, Chair of Baylor College of Medicine's Department of Molecular and Cellular Biology, said, "At that time, people didn't know what hormones did. I knew that when you gave estrogen to the chicken, the oviduct (the passage from the bird's ovaries to the outside) grew pretty big. It was a good model to figure out what was happening inside the cell." Those studies led to that first discovery about the effect of hormones on the nucleus.

"That really changed thinking," said O'Malley. Prior to that, studies of the endocrine system had focused on the physiological effects. By the 1970s, it was time to look deeper at the molecular beginnings. For O'Malley, that deeper look has resulted in unraveling the intricacies of how hormones such as estrogen and progesterone initiate processes of gene transcription and the discoveries of more molecules that actually regulate how those things occur. It's a lifelong obsession that has borne fruit in fields from inflammation to cancer.

His piercing blue eyes flash with excitement as he describes the new finding about one his favorite molecules—steroid receptor coactivator-3 or SRC-3.

"It's important to recognize how beautiful evolution is and how a molecule can be used many ways to get a hormone response just right," he said. He speaks with considerable authority on the subject, given that the first such steroid receptor coactivator was described in his laboratory, a key finding in the field of molecular endocrinology. He has since given spark to the notion that these coactivators are masters of cellular activity.

"The coactivators are master genes. They turn on many genes at the same time," said O'Malley. "They respond to what's going on in terms of the effects of other hormones or stress on the cells. These coactivators receive all of these external signals and then coordinate all the internal events the cell needs for a response."

Coactivators are growing in importance in the field of molecular endocrinology in which O'Malley is a pioneer. The beginning of the field itself can be dated to 1972 when he described how steroid hormones such as estrogen and progesterone act on the nucleus, directly inducing the transcription of the language of genes into new messenger ribonucleic acids or RNAs that are the blueprint for the production of key proteins. These proteins affect the development of hormone-producing tissues, ultimately having implication in a variety of diseases and conditions including cancer and inflammation. That key study and others that followed eventually translated into treatments such as tamoxifen that work directly in this cellular pathway.

Dr. Bert O'Malley and other researchers in 1986

Lab sweet lab: Despite ever-increasing responsibilities during his career, Bert O'Malley, M.D., has stayed committed to laboratory science, as seen here in 1986 with Donald McDonnell, Ph.D., and Orla Conneely, Ph.D.

That was a seminal finding that had its beginnings in the kitchen of O'Malley's grandmother, who predicted his scientific bent as she watched him mix concoctions out of ingredients taken from her cupboards. However, it took a while for him to accept that fate.

"I went to medical school (at the University of Pittsburgh) to be a physician," he said. "I considered many fields—from psychiatry to internal medicine. I worked in a biochemistry laboratory because I needed the money, and in my senior year, I did an elective course with the chief of endocrinology there. I got hooked on research then and just got drawn more and more into it."

That interest took him to the National Institutes of Health in 1965. "It was hard to get in there (at the NIH) and it was very exciting because virtually everyone there was good," he said.

By 1967, he had become head of the Molecular Biology Section of the Endocrine Branch at the National Cancer Institute, but in 1969, academia lured him away to Vanderbilt University School of Medicine in Nashville where he occupied an endowed chair and was named Director of the Reproductive Biology Center, a pioneering effort that crossed departmental lines. It was a model of collegiality that he established in the days to come at Baylor College of Medicine.

"It was a very productive time," he said. He and his colleagues began to determine how the molecular pathway for steroid hormone action worked.

"I think basic science directed toward understanding how something works eventually leads to big breakthroughs," said O'Malley. When the understanding is translated into information directly related to a specific disease, it seems like it is a big event.

"Those findings, however, are always preceded by prior fundamental discoveries related to basic research," said O'Malley. "It is important to preserve basic research in this country so that we can continue to make those findings."

Early in his career, O'Malley settled on the Endocrine Society as his professional touchstone and served as its President in 1985. During his tenure, he pushed for the establishment of the journal Molecular Endocrinology, a move that has proven important in moving the whole area forward.

After four years at Vanderbilt, O'Malley had another big decision to make. He could move his research and his laboratory to Harvard Medical School, Rockefeller University in New York or to a little-known private school in Houston—Baylor College of Medicine.

"Everyone thought I would go to one of the first two. But this place seemed like it was ready to take off. It had a Texas attitude. Come on down here, show us what you can do and you will grow with us," he said. Suffice it to say that he did.

With Michael E. DeBakey, M.D., as President, BCM was poised to dive into basic research. "The leadership said this school won't take off until it really grows through science. That's what put this school in the top 10," said O'Malley. "Now around the country, they say that BCM is a really good science school."

When O'Malley arrived, he found four existing faculty members in his department. Two did not have the credentials necessary for teaching in the medical school and he had to fire them. "I had to fire a nun and a priest," he said. "How was that for a way to start?"

"O'Malley is a pioneer in the field of molecular endocrinology whose work over the past 40 years has provided the scientific framework for understanding a variety of endocrine diseases and cancer. He continues to be a leader in the field."
- Mitchell A. Lazar, M.D., Ph.D.
Professor of Medicine and Genetics
University of Pennsylvania School of Medicine

Jeffrey Rosen, Ph.D., Professor in the department, was one of six faculty members who moved from Nashville to Houston with O'Malley. They were given two floors of laboratories to design and fill with new faculty. O'Malley shepherded his department carefully, while pursing his own research. While others who trained with him at the NIH went on to head institutions, "Bert just wanted to maintain an active research program. He could have become a medical school dean, but I think he gets much more satisfaction out of science," said Rosen.

He and O'Malley still teach a course on gene regulation together, similar to one they started at Vanderbilt. "He still wants to teach this graduate course because it is something he clearly enjoys,"
said Rosen.

Rosen sees the department and the people he has trained as O'Malley's greatest accomplishment.

"He not only built this department, but also influenced the whole field by training so many people. That's a bigger legacy," said Rosen.

David Moore, Ph.D., who came to BCM a decade ago, remembers that the reputation of the department drew him from Boston. "It's not as though Boston is weak in any field of science,
but in specific areas, notably the nuclear receptor area, things are better at Baylor." O'Malley has assembled some of the best minds, making BCM the top place in the world for the study of nuclear receptors.

O'Malley remembers that when he came to the department, there was one grant for $76,000, two students and one postdoctoral student. Now the department is home to 120 postdoctoral students, 75 graduate students and is number one in NIH funding for a U.S. basic science department.

To Mitchell A. Lazar, M.D., Ph.D., Professor of Medicine and Genetics at the University of Pennsylvania School of Medicine, O'Malley is a pioneer in the field of molecular endocrinology "whose work over the past 40 years has provided the scientific framework for understanding a variety of endocrine diseases and cancer. He continues to be a leader in the field."

More than that, he said, O'Malley is a visionary as well. "Science is a puzzle and there are two parts to the scientific puzzle. One is finding the pieces of the puzzle, and I think O'Malley is a leader in that area. But one must also sense what the puzzle is a picture of. That is even more creative than finding the pieces. I think you can find examples of that creativity in Bert O'Malley's work as well."

"He not only built this department—which ranks number one in NIH funding among all biology departments in the nation—but influenced the whole field by training so many people. That's a bigger legacy."
- Jeffrey Rosen, Ph.D.
Professor of Molecular and Cellular Biology
Baylor College of Medicine

Benita Katzenellenbogen, Ph.D., Professor of Cellular and Development Biology at the University of Illinois at Urbana-Champagne, said O'Malley set the tone for inclusive and positive interactions among researchers in the field of molecular endocrinology and nuclear receptors. "I think he has encouraged young scientists and challenged them to do their best possible work," she said.

Ming-Jer Tsai, Ph.D., a Professor in O'Malley's department, said the chair's leadership keeps people at BCM. "All the good people have other job offers. The majority of them have stayed. He has kept the atmosphere here good for science."

Science has remained a priority in his life. "I will do a little of everything else, but I won't ever let my science suffer," said O'Malley.

A supportive and loving wife, Sally, and four children who understood his concentration on science made it possible, he said. "They decided to live with the inconvenience of a scientist who travels and works long hours."

O'Malley once said that opportunity brought him to Baylor College of Medicine and the collegiality of the place—the openness to collaboration—kept him here.

"It's been a good, wild ride and a lot of fun," he said. "The secret is to recruit good people and stay out of their way."

Features

News

Spotlight

Briefs

Development & Alumni News

Volume 3, Issue 2, Summer 2007


	O'Malley's Legacy Grew from Fowl Beginnings by Ruth SoRelle, M.P.H. The luck of the Irish coupled with an enduring dedication to education and research has earned Bert O'Malley, M.D., a place in history in the field of molecular endocrinology. The fascination of Bert O'Malley, M.D., with steroid hormones and their effects on the cell nucleus, genes and the level of gene expression began with a theory and chickens-—many chickens. In an essay published in 1991 in the journal Endocrinology, Peter O. Kohler, M.D., President Emeritus of Oregon Health and Science University, remembered O'Malley and the chickens from their days together in the late 1960s at the National Institutes of Health. "One of my strongest memories is of Bert O'Malley's chicken studies... In order to carry out the experiments, large numbers of chicks had to be injected every six hours around the clock for six successive days. Bert dutifully came in every six hours to make the evening, night and holiday injections. I always believed Bert deserved every accolade after watching him try to reach recalcitrant chickens hiding in the far corners of a side-entry cage in the wee hours of the morning....Those were the halcyon days." Those halcyon days resulted in one of O'Malley's seminal discoveries-—the one most of his colleagues credit with initiating the whole field of molecular endocrinology. O'Malley, Chair of Baylor College of Medicine's Department of Molecular and Cellular Biology, said, "At that time, people didn't know what hormones did. I knew that when you gave estrogen to the chicken, the oviduct (the passage from the bird's ovaries to the outside) grew pretty big. It was a good model to figure out what was happening inside the cell." Those studies led to that first discovery about the effect of hormones on the nucleus. "That really changed thinking," said O'Malley. Prior to that, studies of the endocrine system had focused on the physiological effects. By the 1970s, it was time to look deeper at the molecular beginnings. For O'Malley, that deeper look has resulted in unraveling the intricacies of how hormones such as estrogen and progesterone initiate processes of gene transcription and the discoveries of more molecules that actually regulate how those things occur. It's a lifelong obsession that has borne fruit in fields from inflammation to cancer. His piercing blue eyes flash with excitement as he describes the new finding about one his favorite molecules—steroid receptor coactivator-3 or SRC-3. "It's important to recognize how beautiful evolution is and how a molecule can be used many ways to get a hormone response just right," he said. He speaks with considerable authority on the subject, given that the first such steroid receptor coactivator was described in his laboratory, a key finding in the field of molecular endocrinology. He has since given spark to the notion that these coactivators are masters of cellular activity. "The coactivators are master genes. They turn on many genes at the same time," said O'Malley. "They respond to what's going on in terms of the effects of other hormones or stress on the cells. These coactivators receive all of these external signals and then coordinate all the internal events the cell needs for a response." Coactivators are growing in importance in the field of molecular endocrinology in which O'Malley is a pioneer. The beginning of the field itself can be dated to 1972 when he described how steroid hormones such as estrogen and progesterone act on the nucleus, directly inducing the transcription of the language of genes into new messenger ribonucleic acids or RNAs that are the blueprint for the production of key proteins. These proteins affect the development of hormone-producing tissues, ultimately having implication in a variety of diseases and conditions including cancer and inflammation. That key study and others that followed eventually translated into treatments such as tamoxifen that work directly in this cellular pathway. Lab sweet lab: Despite ever-increasing responsibilities during his career, Bert O'Malley, M.D., has stayed committed to laboratory science, as seen here in 1986 with Donald McDonnell, Ph.D., and Orla Conneely, Ph.D. That was a seminal finding that had its beginnings in the kitchen of O'Malley's grandmother, who predicted his scientific bent as she watched him mix concoctions out of ingredients taken from her cupboards. However, it took a while for him to accept that fate. "I went to medical school (at the University of Pittsburgh) to be a physician," he said. "I considered many fields—from psychiatry to internal medicine. I worked in a biochemistry laboratory because I needed the money, and in my senior year, I did an elective course with the chief of endocrinology there. I got hooked on research then and just got drawn more and more into it." That interest took him to the National Institutes of Health in 1965. "It was hard to get in there (at the NIH) and it was very exciting because virtually everyone there was good," he said. By 1967, he had become head of the Molecular Biology Section of the Endocrine Branch at the National Cancer Institute, but in 1969, academia lured him away to Vanderbilt University School of Medicine in Nashville where he occupied an endowed chair and was named Director of the Reproductive Biology Center, a pioneering effort that crossed departmental lines. It was a model of collegiality that he established in the days to come at Baylor College of Medicine. "It was a very productive time," he said. He and his colleagues began to determine how the molecular pathway for steroid hormone action worked. "I think basic science directed toward understanding how something works eventually leads to big breakthroughs," said O'Malley. When the understanding is translated into information directly related to a specific disease, it seems like it is a big event. "Those findings, however, are always preceded by prior fundamental discoveries related to basic research," said O'Malley. "It is important to preserve basic research in this country so that we can continue to make those findings." Early in his career, O'Malley settled on the Endocrine Society as his professional touchstone and served as its President in 1985. During his tenure, he pushed for the establishment of the journal Molecular Endocrinology, a move that has proven important in moving the whole area forward. After four years at Vanderbilt, O'Malley had another big decision to make. He could move his research and his laboratory to Harvard Medical School, Rockefeller University in New York or to a little-known private school in Houston—Baylor College of Medicine. "Everyone thought I would go to one of the first two. But this place seemed like it was ready to take off. It had a Texas attitude. Come on down here, show us what you can do and you will grow with us," he said. Suffice it to say that he did. With Michael E. DeBakey, M.D., as President, BCM was poised to dive into basic research. "The leadership said this school won't take off until it really grows through science. That's what put this school in the top 10," said O'Malley. "Now around the country, they say that BCM is a really good science school." When O'Malley arrived, he found four existing faculty members in his department. Two did not have the credentials necessary for teaching in the medical school and he had to fire them. "I had to fire a nun and a priest," he said. "How was that for a way to start?" "O'Malley is a pioneer in the field of molecular endocrinology whose work over the past 40 years has provided the scientific framework for understanding a variety of endocrine diseases and cancer. He continues to be a leader in the field." - Mitchell A. Lazar, M.D., Ph.D. Professor of Medicine and Genetics University of Pennsylvania School of Medicine Jeffrey Rosen, Ph.D., Professor in the department, was one of six faculty members who moved from Nashville to Houston with O'Malley. They were given two floors of laboratories to design and fill with new faculty. O'Malley shepherded his department carefully, while pursing his own research. While others who trained with him at the NIH went on to head institutions, "Bert just wanted to maintain an active research program. He could have become a medical school dean, but I think he gets much more satisfaction out of science," said Rosen. He and O'Malley still teach a course on gene regulation together, similar to one they started at Vanderbilt. "He still wants to teach this graduate course because it is something he clearly enjoys," said Rosen. Rosen sees the department and the people he has trained as O'Malley's greatest accomplishment. "He not only built this department, but also influenced the whole field by training so many people. That's a bigger legacy," said Rosen. David Moore, Ph.D., who came to BCM a decade ago, remembers that the reputation of the department drew him from Boston. "It's not as though Boston is weak in any field of science, but in specific areas, notably the nuclear receptor area, things are better at Baylor." O'Malley has assembled some of the best minds, making BCM the top place in the world for the study of nuclear receptors. O'Malley remembers that when he came to the department, there was one grant for $76,000, two students and one postdoctoral student. Now the department is home to 120 postdoctoral students, 75 graduate students and is number one in NIH funding for a U.S. basic science department. To Mitchell A. Lazar, M.D., Ph.D., Professor of Medicine and Genetics at the University of Pennsylvania School of Medicine, O'Malley is a pioneer in the field of molecular endocrinology "whose work over the past 40 years has provided the scientific framework for understanding a variety of endocrine diseases and cancer. He continues to be a leader in the field." More than that, he said, O'Malley is a visionary as well. "Science is a puzzle and there are two parts to the scientific puzzle. One is finding the pieces of the puzzle, and I think O'Malley is a leader in that area. But one must also sense what the puzzle is a picture of. That is even more creative than finding the pieces. I think you can find examples of that creativity in Bert O'Malley's work as well." "He not only built this department—which ranks number one in NIH funding among all biology departments in the nation—but influenced the whole field by training so many people. That's a bigger legacy." - Jeffrey Rosen, Ph.D. Professor of Molecular and Cellular Biology Baylor College of Medicine Benita Katzenellenbogen, Ph.D., Professor of Cellular and Development Biology at the University of Illinois at Urbana-Champagne, said O'Malley set the tone for inclusive and positive interactions among researchers in the field of molecular endocrinology and nuclear receptors. "I think he has encouraged young scientists and challenged them to do their best possible work," she said. Ming-Jer Tsai, Ph.D., a Professor in O'Malley's department, said the chair's leadership keeps people at BCM. "All the good people have other job offers. The majority of them have stayed. He has kept the atmosphere here good for science." Science has remained a priority in his life. "I will do a little of everything else, but I won't ever let my science suffer," said O'Malley. A supportive and loving wife, Sally, and four children who understood his concentration on science made it possible, he said. "They decided to live with the inconvenience of a scientist who travels and works long hours." O'Malley once said that opportunity brought him to Baylor College of Medicine and the collegiality of the place—the openness to collaboration—kept him here. "It's been a good, wild ride and a lot of fun," he said. "The secret is to recruit good people and stay out of their way."		Search all issues: Features Saving Twins Before Birth Blessing to Botswana Preserving Brains Cocaine Vaccine Shows Promise News Building, Bucks & BBQ DNA Discoverer Gets His Own BCM Cancer Center One of Select Few Spotlight Bert O'Malley: A Pioneer in Molecular Endocrinology Making Sense of the Sense of Touch Tissue Samples Go Digital Severe Skin Conditions Take a Back Seat at Camp Dermadillo Health Economist Must Put Price Tag on the Priceless Doctor Creates Cartoon that "Bugs" Kids About the Risks of Tobacco Briefs Living Longer is Smelly Business Clinical Trials for Cancer Southward Bound Green Tea Component Blocks HIV Cell Entry Genetics Technique Takes Bite out of Research Barriers Sports Legends Lend Helping Hands, Arms to College Development & Alumni News Mitchell Gift Furthers Brain Research Lambert Receives Lifetime Achievement Award Kleberg Foundation Gift Establishes RNAi Screening Core Facility Alumnus Named White House Fellow New Trustees Announced Tailoring Technology to Benefit You, the Patient

	Volume 3, Issue 2, Summer 2007



	BCM Home \| BCM Intranet \| Privacy Notices \| Contact BCM \| BCM Site Map © 2005-8 Baylor College of Medicine® Office of Public Affairs One Baylor Plaza, Houston, Texas 77030 Mail: One Baylor Plaza, Mail Stop 106, Houston, Texas 77030 Phone: 713-798-4710 \| Fax: 713-798-3692 E-mail: solutions@bcm.edu