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Research: Employee Profiles

Annual Report - 2006-2007

Viral Attack


By Scott Merville

Juan Fueyo, M.D. and Candelaria Gomez-Manzano, M.D.

As a neurology resident in one of the largest hospitals in Barcelona, Juan Fueyo, M.D., had two patients with an extremely rare brain disease caused by a cancer in their lungs.
 
His work on those cases with a leading Spanish neuro-oncologist nudged Fueyo toward a career in research and on the road to M. D. Anderson, where he has led the development of a brain cancer-killing virus now headed for a clinical trial.

Fueyo, along with his wife and research colleague Candelaria Gomez-Manzano, M.D., came to M. D. Anderson in 1994 as a postdoctoral fellow.

The couple, who have three children and independent labs in M. D. Anderson’s Department of Neuro-Oncology, collaborate with others on Delta-24-RGD, a virus designed to destroy a highly resistant and lethal form of brain cancer known as glioblastoma multiforme.

“Our research interests are complementary,” Fueyo says. Gomez-Manzano studies cancer stem cells and angiogenesis (the birth of new blood vessels) while Fueyo focuses on virology.

These interests came together in a study showing Delta-24-RGD kills brain cancer stem cells, which are thought to drive tumor growth.

The research team led by Fueyo, study co-senior author Frederick Lang Jr., M.D., professor in the Department of Neurosurgery, and first author Hong Jiang, Ph.D., instructor in the Department of Neuro-Oncology, characterized four brain tumor stem cell lines from four specimens of glioblastoma multiforme. Each line exhibited the characteristics and protein signatures of stem cells. Delta-24-RGD succeeded in killing all four types.

Researchers then grafted the cancer stem cell lines into the brains of mice and treated the resultant tumors with injections of Delta-24-RGD. Mice treated with Delta-24-RGD survived longer than those left untreated. Two of the eight treated mice survived until the end of the experiment, with no neurological symptoms.

“In evaluating an experimental cancer treatment, it’s important to see improvement in survival in the majority of animals, but for some to be cured and survive a long time without neurological symptoms is rare,” Fueyo says.

These results have led to the development of a clinical quality version of Delta-24-RGD by the National Cancer Institute. A clinical trial testing the virus in patients with glioblastoma multiforme is expected to begin soon. 

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Aging and Cancer


By Mary Jane Schier

Sandy Chang, M.D., Ph.D.

The telescope he received for his 10th birthday propelled Sandy Chang, M.D., Ph.D., toward becoming an award-winning physician-scientist at M. D. Anderson.
 
The gift allowed him to view the belts of Jupiter and the rings of Saturn before he designed and built a larger telescope that took second place in the 1984 Westinghouse Science Talent Search and provided a college scholarship. His early fascination with astronomy evolved into a keen interest in the molecular mechanisms of human diseases and motivated him to earn a Ph.D. at The Rockefeller Institute and a medical degree from Cornell University Medical College.

After a residency in clinical pathology at Brigham and Women’s Hospital and a postdoctoral fellowship at the Dana-Farber Cancer Institute, Chang came to M. D. Anderson five years ago. Since then, he has advanced understanding of the role of telomere function in senescence (aging) and cancer. He wants to know how telomeres, the repetitive DNA sequences at the ends of chromosomes, maintain genome stability.

“When we fully understand telomeres, then we’ll appreciate how they protect us as well as contribute to both the aging process and cancer. In time, I think it will be important to assess telomere status prior to planning targeted therapies for cancer patients,” explains Chang, associate professor in the Departments of Cancer Genetics and Hematopathology.

Chang’s laboratory generated the first mouse model of human Werner Syndrome to probe the interaction between telomere dysfunction, genomic instability in aging and development of cancer. A rare disease that strikes adults in their 30s, Werner Syndrome is marked by premature aging and early onset of cancer. Most recently, his group discovered a key protein that is essential to maintain telomere stability.

In addition to his research, Chang directs the T. C. Hsu Molecular Cytogenetics Laboratory, an institutional core facility he developed to help colleagues perform experiments. He teaches future scientists at The University of Texas Graduate School of Biomedical Sciences and Baylor College of Medicine’s Huffington Center for Aging in Houston.

During 2007, Chang was one of three junior faculty chosen for an M. D. Anderson Faculty Scholar Award for outstanding achievements and dedication to excellence. He also received the Academy of Clinical Laboratory Physicians and Sciences’ Ellis S. Benson Award, recognizing meritorious accomplishments by a young specialist in laboratory medicine. 

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Harnessing the Immune System


By Mary Jane Schier

Larry Kwak, M.D., Ph.D.

Larry W. Kwak, M.D., Ph.D., decided to become a physician-scientist because he wanted to combine caring for cancer patients with conducting research that would improve their survival rates.
 
“That dream still drives me every day,” he confides.

Kwak was well known for developing a vaccine against non-Hodgkin’s lymphoma when he was recruited from the National Cancer Institute in 2004 to chair M. D. Anderson’s Department of Lymphoma and Myeloma. He also is associate director of the Center for Cancer Immunology Research.

While at NCI, Kwak showed that a vaccine for follicular low-grade lymphoma was effective in mice, coordinated the first-in-human clinical trial and initiated three, late-stage multicenter trials involving more than 500 patients each.

At M. D. Anderson, he leads the development of new vaccines, including a second generation vaccine made with a genetically engineered chemokine molecule for patients with low-grade lymphoma. A first-in-human clinical trial will start this year as part of a large U.S. Department of Defense grant.

Kwak is especially encouraged about a customized vaccine for patients with relapsed myeloma developed in his laboratory and now undergoing early clinical evaluation in collaboration with Study Principal Investigator Sergio Giralt, M.D., professor in the Department of Stem Cell Transplantation and Cellular Therapy, and Richard Champlin, M.D., chair of the department. This translational research is being expanded through a five-year, $6.25 million grant from the Leukemia and Lymphoma Society.

“The new grant is one of three Marshall A. Lichtman Specialized Center of Research grants awarded by the society in 2007. It provides important support for developing vaccines that can summon an immune system attack against both multiple myeloma and acute lymphocytic leukemia,” explains Kwak, the grant’s principal investigator.

Ten multiple myeloma patients whose disease had relapsed after therapy have received the myeloma vaccine, which is made from healthy matched T cells collected from patients’ siblings. About 20 more patient-sibling pairs likely will participate in the early vaccine study.

“I’ve been intrigued with the idea of harnessing the immune system since I first heard about it while working in a research lab in high school,” Kwak recalls. “Now I’m increasingly optimistic about our ability to develop vaccines and other targeted therapies that, in combination with chemotherapy, should improve the outlook for many patients.”

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