If the proverb that says two heads are better than one holds true, then one can just imagine what 40-plus heads might accomplish.
Steven Goodman, Ph.D., and director of the Institute of Biomedical Sciences and Technology (IBMST) at The University of Texas at Dallas, should soon find out for himself whether a multi-headed approach to research yields more powerful and impressive results.
After 23 years of conducting research at medical schools, he thought it might be better to attack a problem on many fronts at the same time. And thanks to the Human Genome Project, which allowed scientists to map and identify the genes of the human body, and proteomic and bioinformatic tools, such approaches can be attempted.
“I realized that, post-human genome, the types of science that needed to be done required a more diverse group of expertise than one finds within medical schools. Medical schools have wonderful basic science departments but they don’t really have chemists and physicists and mathematicians and engineers and computer scientists, and I felt that those folks were needed, as well as the physicians and biologists, to be involved in the science that I wanted to do.
“I shared that vision with the leadership here. And UTD president [Franklyn] Jenifer, effective Jan. 2003, created the Institute of Biomedical Sciences and Technology and asked me to be its first director,” Goodman said.
The growth of IBMST has been impressive. The institute features four focus groups: diseases of the aging brain; molecular diagnostics and biomolecular technology; blood disorders; and bioengineering, security and defense.
“We started with 11 faculty members, all from UTD. And a year and a half later, we have 46 faculty members from six different universities and medical schools. Some of them are from UTD, U.T. Arlington, U.T. Brownsville, U.T. Southwestern Medical Center and Texas A&M Medical Center, and the Baylor Research Institute,” he said.
“Each one of us has our own individual funding that supports our own research, but, in addition to that, over the last academic year we put in almost $20 million worth of interdisciplinary grant proposals and now we are waiting to see the fruits of that effort,” Goodman said.
Sickle cell research
Sickle cell anemia, a blood disorder affecting mostly African-Americans, falls under the gaze of the IBMST. And Goodman has done extensive work in the area, formerly heading sickle cell disease research centers at UTD and at the University of South Alabama.
“My major interest has been in sickle cell disease. I, along with George Buchanan, M.D., at U.T. Southwestern Medical Center, brought the National Institutes of Health’s Sickle Cell Center here to Texas three years ago,” Goodman said.
Buchanan is a U.T. Southwestern professor of pediatrics and director of hematology/oncology at Children’s Medical Center in Dallas. He also heads the sickle cell program there.
“As early as the 1950s, we knew there were two forms of sickle cells: reversibly sickled cells and irreversibly sickled cells. The latter always stay in the sickle shape, independent of whether the hemoglobin is oxygenated or deoxygenated and independent of whether the hemoglobin S is polymerized or depolymerized.
Until Goodman proved otherwise, it was thought irreversibly sickled cells were just that – irreversible.
“They [irreversibly sickled cells] can represent anywhere from the low side – two percent of all red blood cells – up to 45 percent of the total red blood cells in the circulation of the sickle cell patient. They are thought to be key players in the blockage of blood vessels,” he said.
“In sickle cell research,” Goodman continued, “the major thing that my lab has accomplished is working out the molecular basis of the irreversibly sickle cell and trying to figure out how one can keep them from forming.”
“The thing that worked the best was N Acetyl -Cysteine (NAC). It is a very effective antioxidant. But also, when it enters into cells, the acetyl group comes off and you’re left with L-cysteine, a precursor in the metabolic pathway to reduced glutathione. So the cells now have their own protection from oxidative damage.
“The result was that, in vitro, we were able to block the formation of irreversibly sickled cells. We also were able to do what we thought impossible, which was convert irreversibly sickled cells back into biconcave cells,” Goodman said. The drug also blocked dehydration of sickle cells, he said.
Glutathione is described in Webster’s as the product of an amino-based chemical reaction that plays an important role in oxidation-reduction processes.
NAC has been used since the 1960s in clinical trials for all kinds of diseases and is considered a safe drug, even when used at very high doses, according to Goodman.
“In a phase 2 human trial we were able to lower the crisis rate in people taking the highest doses [of NAC] by greater than 50 percent, which is good because it matches the rate of another drug, hyroxyurea, which is currently a drug in use,” he said.
However, he warned that NAC must complete Phase 3 trials before it can be recommended by physicians for use by patients.
One step beyond
Now Goodman has begun a major project that’s going to take at least the next five years and probably is the single biggest undertaking in the sickle cell field, he said.
“Using the techniques of proteomics – the study of protein systems, their forms and functions – I’m trying to figure out why we have such a difference in clinical severity among patients with sickle cell disease. This ranges all the way from very young children who have more than 10 crises a year and die at a very young age to people who rarely ever have a crisis and live into their 70s. They all have the same primary genetic defect, which means that there needs to be other differences that explain that particular conundrum. We are trying to look at the complete proteome of red blood cells, which is where the primary defect occurs,” Goodman said.
The IBMST team recently applied for a grant seeking roughly $5 million for the study, which Goodman said they’ve already started.
“In a study like this, I calculated that we would derive about a half billion ratios, which means you also need mathematicians and statisticians and the computer scientists to write the necessary programs in order to analyze this much data. Only at an institute such as IBMST would you have the diverse, multidisciplinary expertise to be able to pull off research like this,” Goodman said.
“We are looking at the proteome in patients with the severe form of the sickle cell disease and those with the mild form of the disease. Every single situation where a protein is changing drastically, either in terms of its amount or in its modifications, is of interest to us. Contributors to the process of vasoclussion (blocking blood vessels) are not only the red blood cells, which are very important, but also the white blood cells, especially monocytes and plasma. Monocyes are very adhesive to the endothelial walls (lining) of the blood vessel, in the case of sickle cell disease,and also adhesive to the sickle cells themselves.
“So if one wanted to have a complete look at what factors might be changing to cause vasocclusion – and the more vasocclusion you get, the more crises you have, the more crises you have, the more severe disease you have – you need to look at the red blood cells, the white blood cells and at the plasma because you cannot get the complete story without looking at all of them in terms of protein changes,” Goodman said.
Despite his earlier accomplishments, Goodman said, “The most important thing in my career will be what we are doing right now.”
Creative juices flowing
When he became director of IBMST, the administration offered to ease his workload, but he didn’t take it seriously. “What it did allow me to do was to teach only what I felt I wanted to teach,” Goodman said.
As a result, Goodman said, he created two new courses, both core courses for the new masters program in biotechnology at UTD. One is on proteomics, which he described as being equally populated by graduate students and undergraduates. He also is teaching a biotechnology laboratory course with other members of the IBMST faculty.
Goodman said he also is excited about two other courses created by IBMST faculty members: Applied Bioinformatics, the quantitative and statistical analysis of biological sequence and structural information, taught by Steve Levene, Ph.D.; and Genomics, the study of genetic sequencing, taught by Betty Pace, M.D.
“What excites me is coming up with new courses that are current and that really will prepare the students for what’s going to be their future, independent of whether their future is in academic biological research or whether it’s in the biotech industry or whether it’s as a medical student or dental student. They are going to need these courses because that’s where the field is going,” Goodman said.
Also, as of Jan. 21, he became president of the Association of Anatomy, Cell Biology and Neurobiology Chairs.
The organization represents all of the chairmen and directors of institutes at all of the schools and universities that cover anatomy, neurobiology and cell biology in the United States, Canada and Puerto Rico.
“It is my responsibility to create the annual meeting for 2006. This meeting is going to take place in Aruba, January 18 through the 21.
“My real passion these days is to putting together people of very diverse backgrounds. I decided that the theme of this meeting would be ‘The Future of Interdisciplinary Research and Training: Breaking Down the Barriers.’
“We have three Nobel laureates coming to the meeting: Professor Aaron Ciechanover, Professor Russell Hulse and Professor Alan MacDiarmid,” Goodman said. “We’d like them to talk about their research, but will also involve them in round table discussions related to the future of interdisciplinary research and training.”
- Updated: February 6, 2006
