Teamwork

Baylor's Institute for Biomedical Studies proves a beneficial collaboration for students, researchers alike

Imagine probing the secrets of the immune system,working to relieve chronic knee pain or studying the neurobiology of a notorious "date-rape" drug.

Baylor's Institute for Biomedical Studies (BMS) gives students a chance to do all that and more.

Since its first full year of operation in 1991-92, BMS has grown to include 23 graduate students pursuing medical research opportunities on both the Waco campus and at Baylor University Medical Center (BUMC) at Dallas, says Robert Kane, an associate professor of chemistry who directs Baylor's Center for Drug Discovery and is interim BMS director.

University-appointed Dallas faculty members regularly interact with Waco students to teach one or two lecture courses a semester, participate in videoconferencing and provide career-building advice in the BMS Seminar class, a parallel course taught in both Waco and Dallas in which recent topics have included intellectual property rights and good manufacturing practices. BMS students finish the majority of their coursework in Waco and then participate in a 12-week rotation that exposes them to four different research laboratories and helps them determine the one in which they will do their graduate research, says Kane, who came to Baylor in 1996 following a National Institute of Health postdoctoral fellowship. 

The association between the University and BUMC, the second-busiest hospital in the Dallas-Fort Worth area, has strengthened both institutions, says William Hillis, BS '53, a Johns Hopkins-trained specialist in virology (the study of viruses) and immunology, who has served in many academic and administrative roles at Baylor. As chair of biology in the 1980s, Hillis served on a committee investigating ways to strengthen the relationship between Baylor and what is now BUMC. The BMS program was one result of that self-study.

"The intent was to have some of our graduate students in the biomedical sciences at Baylor have an opportunity to actually be engaged in some human medical research that might serve as a basis for their master's theses. We, at that time, did not have a PhD in biology. Gradually, as that institute became better organized, we started making appointments to the BMS program and the degree programs began to multiply," says Hillis, the Cornelia Marschall Smith Distinguished Professor of Biology.

Meanwhile in Dallas, Boone Powell Jr., president and chief executive officer at the medical center from 1980 to 2000, was eager to create a formal association, Hillis recalls.

The partnership has worked beautifully: improving the medical center's ability to get research grants by being attached to a university and providing it with a steady flow of well-trained graduate students, who in turn get the chance to work on progressive research early in their careers, Hillis says.

During the past two decades, BUMC has been expanding its research base by capitalizing on the medical center's core strengths in transplantation and immunology. That vision led to the 1982 founding of Baylor Research Foundation, now the Baylor Research Institute (BRI), which oversees all BUMC medical research -- 550 active research protocols at the end of 2005, says BRI President Michael A.E. Ramsay, a world-renowned anesthesiologist and co-creator of the Ramsay Scale used by hospitals worldwide to assess a patient's level of sedation.

"Our whole focus is on what I call clinically relevant research," Ramsay says, meaning research that will benefit patients as soon as possible. "That is now what the National Institutes of Health has emphasized, taking their lead from us, as of last year."

That approach has many benefits to Baylor and BUMC, he says. "When you are doing cutting-edge research, you attract the best physicians, the best researchers and the best health care workers. This pays off enormously for the students in having the best teachers, seeing the research in action and participating in the work."

Word is getting out. A case in point is Baylor graduate student Chun-I "Junnie" Yu, who was working at a mouse laboratory in Taiwan when she read a paper written by a researcher at BUMC, Jacques Banchereau, that changed her life. Yu was inspired to write asking to join his work, which has the potential to improve the lives of cancer patients, transplant recipients and flu sufferers.

In 2003, Yu completed her coursework in Waco and immediately began work in the laboratory of Banchereau's colleague Anna Karolina Palucka in Dallas.

Banchereau and Palucka are two of the original investigators in one of BRI's newest strategic initiatives, the Baylor Institute of Immunological Research (BIIR), established 10 years ago by Banchereau, the former director of the Schering-Plough Laboratory for Immunological Research near Lyon, France, where he was one of the first scientists in the world to grow human dendritic cells (DCs).

Banchereau is the lead author of the 1998 Nature paper, "Dendritic Cells and the Control of Immunity" (Nature, 392: 245-52, 1998) -- the sixth most-cited paper of the last decade, according to The Scientist magazine's October 2002 issue -- that helped usher in the dendritic cell era in medical research.

DCs are named for their treelike projections called dendrites. The cells once were regarded as unimportant, but in part due to Banchereau's work, they are now known to act as sentries that recognize foreign invaders and present their antigens to the immune system, which makes antibodies against the interlopers. The antigen-antibody reaction is at the basis of the immune response.

That response can be both beneficial, as in the case of a foreign virus or bacteria, or problematic, as when the immune system targets a transplanted organ or a person's own cells in autoimmune diseases. Clearly, learning to manipulate DCs holds the potential to treat many diseases and conditions.

The National Institutes of Health has awarded several grants to Palucka for her efforts to manipulate the immune system to fight cancer. Since 1999, Palucka and Banchereau have conducted Phase I and Phase II clinical trials of highly personalized cancer vaccines in 80 patients with treatment-resistant stage IV malignant melanoma, a condition with a bleak prognosis. Approximately 80 patients have been vaccinated and the results are encouraging, Palucka says.

"What we've found is that the dendritic cell vaccines can induce immune responses against melanoma and in some patients they can induce durable regression of tumors," she says. In fact, four of the original 18 patients remain alive more than five years after entering the study and many others have survived at least two years.

Unlike traditional cancer therapies, the vaccine approach has virtually no side effects. "So far, the safety profile has been amazing," she says.

"You can draw a parallel that what we are trying to do is much like what people are trying to do with the flu vaccine," she says. When a person gets the flu vaccine, the dendritic cells in the patient's body will pick up vaccine antigens, and then educate the immune cells in the blood to recognize them and protect the person by forming antibodies, Palucka says.

For Yu's graduate research project, she is working to develop a deeper understanding of the human immune response. In order to test the DC therapy, Banchereau and Palucka created a special mouse, the HuMouse, that lacks its own immune system and has been given a human one. Yu is using the HuMouse to study the human immune system's response to human influenza virus, which causes flu in people but fails to sicken mice.

The HuMouse is a unique model for influenza, says Yu, who recognizes her fortune in being associated with the project. "I think everybody would think I am lucky to be able to do this kind of work," she says.

Palucka says the feeling is mutual. "I have an absolutely wonderful student who is working with me on the HuMouse," she says, referring to Yu, and added that the plan is to expand the vaccine research into breast cancer with the HuMouse central to that effort. "We hope that this program will be strengthened so we can have more students." 

Certainly having world-famous researchers in Dallas doing applied biomedical research that quickly gets transferred to actual patients is a big pull, but there are also amazing research projects going on in Waco, says Brandi Wasek, one of the first students to participate in the 12-week rotation program that began last summer.

"The rotation program was great. Previously, students had to basically choose who they wanted to work under just from hearing about the research," she says. "We got to see it."

Her first rotation was in the Waco neuroscience lab of N. Bradley Keele, BS '90, where she studied the brain's response to different chemicals. During those three weeks with Keele, an associate professor who holds a doctorate from the University of Texas Medical Branch in Galveston, she learned to inject substances into rats' brains.

Next, she worked in Kane's lab in collaboration with the School of Engineering and Computer Science on a tissue-repair technology that is the subject of a recently filed patent application. This technique shows promise for repairing damage to a shock-absorbing part of the knee called the meniscus. Wasek tested various photochemicals on bovine meniscus tissue to study the substances' ability to bond the tissues when exposed to light, she says.

Then Wasek spent six weeks living at the nursing residence hall in Dallas and working in two labs at BUMC. The first was Douglas M. Smith's immunology laboratory, which provided a thorough introduction to the competing demands of clinical and basic research in the biomedical sciences, she says.

Her fourth rotation was in Teodoro Bottiglieri's laboratory, where research is focused on metabolic pathways that are involved in the pathophysiology of vascular disease and brain disorders, including Alzheimer's and Parkinson's disease, and depression. Another area of research studies brain function effects of gamma hydroxybutyrate (GHB) -- also known as the "date-rape" drug because of crimes in which offenders put the substance into victims' drinks. 

She chose Bottiglieri's lab for her graduate research and is looking forward to him sending her descriptions of some of his recently funded grants on which she can elect to work.

"He has many, many projects. I'm not even sure which one I'm going to work on yet," she says, adding that the BMS program has exceeded her expectations.

"I've heard that at a lot of other colleges when you go into a lab it's so large and you have so many people over you that you are just the "go-to guy" for mixing solutions and doing what undergraduates could do," Wasek says. "At these labs, you are respected."