Translational Research The Houston Methodist Research Institute focuses primarily on translational research — aiming to bridge the gap between laboratory science and clinical research through multidisciplinary approaches designed to speed up the development of new therapies and new cures. This “bench to bedside” approach is reflected in the research currently underway here, with physicians, scientists, and engineers using cutting-edge technologies, creativity, and ingenuity to develop new treatments for disease.
Bioinformatic approaches to medical research
Dr. Stephen Wong is holder of the John S. Dunn Distinguished Endowed Chair in Biomedical Engineering, director of the bioengineering and bioinformatics programmatic core, and Chief Research Information Officer at the Houston Methodist Research Institute. In an example of the distinctly different approach the Research Institute takes toward scientific disciplines, Dr. Wong is a computer scientist, bioengineer, medical physicist, and systems biologist, rather than a medical doctor.
Drug repositioning One challenge that Dr. Wong and his collaborators are addressing is the slowing pace of new drug development. This is partly the result of the extended process required to bring a new drug from development through clinical testing to final regulatory approval, and partly the result of scientists’ running out of known biological targets to hit. Dr. Wong’s team is instead using computer algorithms to search for existing or approved drugs whose side effects and mechanisms may make them applicable to other illnesses. In one example, he and his team have identified a new use for a drug, dasatinib, already approved to treat certain types of leukemia. Based on his computer analysis, he has identified it as a candidate for use against breast cancer stem cells. A second drug, sunitinib (used to treat certain kidney cancers) may also be effective against breast cancer metastasis to the brain. Since these drugs are already FDA approved, they have gone directly to Phase II clinical trials under the direction of Dr. Jenny Chang, Director of the Houston Methodist Cancer 8
Houston Methodist Research Institute
Center. In effect, Dr. Wong’s approach has reduced from 10 years to 18 months, the time it takes to move an investigational drug into the clinical trials stage.
Cancer stem cell modeling Cancer stem cells are known to be the precursor cells from which cancer cells are created; some consider them the “root” of cancer. These cells are, however, extremely difficult to isolate. Using advanced microscopic imaging and molecular biology techniques, Dr. Wong and his team are working to develop a better understanding of breast cancer stem cells, and to create mathematical and computational models for simulating their behavior. Dr. Wong received a National Cancer Institute Center Grant, supporting research in this field at the new Center for Modeling Cancer Development. By learning how these cells react to different types of stimuli, Dr. Wong hopes to develop a comprehensive computer model that can accurately predict the response of these elusive stem cells to different medications. If he and his team are successful, they will have created an accurate, virtual stem cell that can help predict the response of these stem cells to different medications — potentially helping predict what drugs will be effective in preventing cancer from spreading, or even killing it off altogether.
Image-guided intervention for lung, prostate, and breast cancer With many types of lung cancer, diagnosis alone can require as many as four different imaging studies and image-guided biopsy procedures. Dr. Wong and his team
2 are working to develop a new system using 3D molecular imaging to guide a fine needle into potentially cancerous nodules in a patient’s lungs, view the nodules through an integrated microscope, and draw cells from the nodule for testing. If these nodules prove cancerous, the same system will be used to destroy them using radiofrequency ablation — pinpoint pulses of high-frequency energy. Partnering with the surgeons at Houston Methodist, Dr. Wong and his team are extending their image-guided device platform for use in prostate and breast cancer cases as well. This work was supported by a grant from the Cancer Prevention Research Institute of Texas (CPRIT).
New approaches to combat neurodegenerative disease In another project, Dr. Wong and his team are using advanced computational analysis and high-throughput imaging to gain new understanding of, and develop new treatments for, neurodegenerative diseases such as Alzheimer’s disease. This computerized approach, based on rapid imaging and analysis of the billions of neurons and trillions of synapses that make up the human brain, was jumpstarted by a multi-million dollar donation from the Ting Tsung and Wei Fong Chao Foundation.