Institute of Biotechnology gains momentum

By Will Sansom

A gene that stops cancer. Cells that control obesity and diabetes. Nerves that might point the way to treating muscular dystrophy.

These and other molecular frontiers are being explored by geneticists at The University of Texas Institute of Biotechnology (IBT). Work at the IBT could have profound effects on diagnosing and treating a host of diseases and conditions.

Research at the institute is yielding exciting results in laboratory animals findings that one day may have significant implications for human health.

The IBT represents a second generation of research and development that began with the opening of The University of Texas Health Science Center at San Antonio. And now, 2 1/2 years since scientists first filled the IBT laboratories, the institute already is making a major difference in the region's basic research activities.

The IBT is part of a new vision that, in less than 10 years, has turned hundreds of acres of Bexar County brushland into a promising new research mecca - the Texas Research Park. The research park is a place where research - and its clinical applications - are thriving, and it's a place where there is plenty of room to grow.

If this scenario sounds familiar, it's because it was played out some four decades ago, when the South Texas Medical Center in San Antonio was just a glimmer in visionary eyes. Now, thousands of health care providers, researchers and support personnel work in the medical center's many institutions, including its crown jewel, the Health Science Center.

Pioneering cancer geneticists Wen-Hwa Lee, PhD, and his wife, Eva Lee, PhD, moved their laboratories to the IBT from Southern California in 1991. Joining a handful of researchers from the Health Science Center, they began to recruit faculty and staff for the brand-new facility.

Except for the laboratories of IBT Deputy Director Z. Dave Sharp, PhD, the $10 million Hayden Head Building was largely vacant when the Lees arrived. But things soon changed.

Under the leadership of Dr. Wen-Hwa Lee, who is cross-appointed in cellular and structural biology, the IBT has evolved as a dynamic component of the Health Science Center. The institute is a haven of unbridled scientific pursuit and optimism, situated in a scenic natural setting between San Antonio and the quiet farming community of Castroville.

In two short years, the IBT has expanded almost threefold from the Lees' teams of 20 researchers and Dr. Sharp's team of five researchers. Ten IBT faculty now run their own laboratories, and they are helped by 14 graduate students, 16 post-doctoral research scientists and a group of a dozen or more technicians. Including the support people who help the IBT run, the institute is the central workplace for nearly 80 people.

"We anticipate that, when we're fully staffed, we will employ 110 to 120 people," said Dr. Wen-Hwa Lee, who is IBT director.

With a host of research projects up and running, the IBT's national and international prominence is growing quickly. Grant support from the National Institutes of Health (NIH) increased 800 percent from 1991 to 1992, and the IBT's total of federal support for the next three to four years is $6 million. The institute ranked 12th in NIH funding in 1992 among similar departments in the United States, up from 35th the previous year.

In just two years, IBT faculty members have established a national reputation. They have published 22 original research articles, and another is soon to be published in the international journal Nature. IBT investigators serve on a number of NIH peer-review study sections. Dr. Eva Lee was invited to give presentations at the prestigious Cold Spring Harbor Laboratory and the University of California at San Diego. Dr. Wen-Hwa Lee was invited to speak at Stanford, Harvard, University of Michigan, the American Association of Cancer Researchers Symposium at Galveston, and many other major symposiums.

"For a young institute with a lot of young faculty, it's all very exciting," he said.

Faculty also helped start the Texas Triangle Meeting, an annual meeting of geneticists that rotates between the IBT, the UT M.D. Anderson Cancer Center and the UT Southwestern Medical Center at Dallas. The IBT hosted the first of the meetings in 1992 and faculty traveled this year to M.D. Anderson for the meeting.

The IBT's seminar series, inaugurated in April 1991, has drawn distinguished speakers from the nation's cradles of molecular biology and genetics. Visitors have hailed from Stanford, Princeton, Johns Hopkins, Duke, Baylor College of Medicine, UT Southwestern, Texas A&M, Cold Spring Harbor Laboratory, the University of California at San Francisco, and UCLA.

In addition, IBT scientists regularly hear presentations about the studies of their colleagues at the Health Science Center and at other local institutions such as the Southwest Foundation for Biomedical Research.

The IBT, a three-story building, consists of four sets of laboratories on the second and third floors. Support services include a transgenic mice laboratory, a facility for breeding transgenic fruit flies and a room containing an ultra-powerful microscope and computer package that can capture multiple images of a cell and, using these images, construct detailed three-dimensional representations of the cell's structure.

Steady growth for the young institute is still expected. A new interdepartmental degree program in molecular medicine sponsored by the IBT is on the horizon, pending final approval by the Texas Higher Education Coordinating Board.

"The scientists of the IBT were chosen for their potential to make important contributions in molecular medicine," Dr. Wen-Hwa Lee said. "It is the firm conviction of every scientist at the IBT that molecular biology is the primary force driving the future development of treatments for a wide variety of human maladies.

"Every project at the institute is either directly or indirectly focused on the problems fundamental to disease," he said. "We look forward to a future of continued development and, especially, toward the many exciting discoveries from our institute that will contribute to the health and well-being of everyone."

These are some of the researchers at the IBT, and their projects:

-- Robert Christy, PhD, is studying the genetic pathway to fat cell development. He's looking at pre-adipocytes, which are precursor cells to fat cells. If scientists can learn how cells become committed toward adipocyte development, they may one day learn how to control obesity, diabetes and other health problems.

-- Steven Britt, MD, is studying rhodopsin, a light receptor that is important in vision. When light enters the eye, the rhodopsin molecule becomes activated. Dr. Britt's work, which involves studying rhodopsin's effects on the vision of transgenic fruit flies, may have important implications for diseases such as retinal degeneration. Transgenic animals are animals that may be genetically altered for the purpose of studying disease.

-- Paul Gardner, PhD, is studying points in the body where nerves and muscles come into contact. These neuromuscular junctions are believed to be critical for nerves' communication with muscles. Dr. Gardner's work may have implications in the treatment of degenerative muscle diseases such as muscular dystrophy.

-- Wen-Hwa Lee, PhD, is continuing his pioneering research of retinoblastoma, a childhood eye cancer. Dr. Lee's laboratory is cloning proteins associated with the retinoblastoma gene, which is called a "tumor-suppressor" gene because it regulates cell growth.

-- Eva Lee, PhD, also is working with retinoblastoma. She and her collaborators have engineered a mouse in which both copies of the retinoblastoma gene are "knocked out," or defective, and have observed formation of tumors and other interesting results. "This mouse model should be a valuable resource for trying to work out therapies or maybe even gene replacement to correct the hereditary tendency toward getting cancer," she said.

"Retinoblastoma is the prototypical tumor-suppressor gene," said Dr. Sharp. "Several of these suppressors have been discovered, but RB is one of the best understood and the Lees lead the pack in understanding how it works."

-- Barbara Christy, PhD, is studying the role of gene regulatory proteins in the development of mouse embryos, as well as the role of these proteins in controlling growth in cultured cells. She hopes to identify other genes that are targets for regulation by these proteins. These genetic regulators may play a key role in abnormal development that results in numerous human diseases.

-- Eduardo Montalvo, PhD, and his team are studying molecular aspects of the Epstein-Barr virus, particularly factors involved in replication of the virus. The laboratory's long-term objective is to help in the development of therapies for human diseases.

-- Edward Seto, PhD, is studying the way in which proteins collaborate to control transcription of genes important in metal detoxification -- the process by which our genetic material is copied into RNA, which can be used to produce proteins such as enzymes.

-- Dr. Sharp's laboratory is examining a regulatory protein involved in pituitary development. The protein, called Pit-1, appears to activate development of cells that produce growth hormone, prolactin and thyroid stimulating hormone.

-- Alan Tomkinson, PhD, is exploring the relationship between DNA damage, DNA repair and carcinogenesis (the development of cancer). Damage to genetic material appears to play a substantial role in a number of hereditary, cancer-prone human diseases (xeroderma pigmentusum and Cockayne's syndrome).