Recent Developments At The Burnham Institute For Medical Research, Dec. 2008
A mutation in the gene coding the protein dystrophin has long been known to be associated with muscular dystrophy, but the role the protein plays in the disease was unknown. Lorenzo Puri, M.D., Ph.D. and colleagues have discovered that the dystrophin mutation causes an increase in the amount of the histone deacetylase enzyme, HDAC2. Increased HDAC2 activity alters the gene expression profile in the diseased muscle cells compared to normal muscle cells. By inhibiting HDAC2 with small molecule compounds or RNA interference, Dr. Lorenzo was able to return the muscle cells with the dystrophin mutation to normal histology and function. This advancement may lead to novel therapies for muscular dystrophy.
Microscopic Race for New Cures
Jeff Price, M.D., Ph.D. has created a next generation robotic microscope which can be used for high-throughput cellular image analysis to discover new potential drugs. The novel instrumentation utilizes chromatic aberration - the difference in focus between different colors of light in optical systems - to simplify and speed auto-focusing of the microscope via digital color cameras. This advancement will increase screening from the 20,000 -- 40,000 compounds possible per day with existing technology, to more than 100,000 screens per day, a five-fold increase in productivity.
Nanoworms Make Tumors Squirm
Nano-scale worms made out of iron oxide (rust) may be the next big breakthrough in cancer treatment. Erkki Ruoslahti, M.D., Ph.D., along with collaborators at the University of California, San Diego and the Massachusetts Institute of Technology, has shown that iron oxide nanoworms can bind to tumors when coated with tumor-homing peptides. The team is now attempting to design nanoparticles that will seek out tumors in the body, send a diagnostic signal and release a drug at the site of the tumor in a controlled manner.
What's in Fashion: Designer Drugs to Block Breast Cancer
Gregory Roth, Ph.D., and colleagues have determined that a biologically active molecule called a chemokine promotes the spread of tumors, particularly in breast cancer. Dr. Roth believes that compounds that block the chemokine may be potential cancer therapies. However, existing small molecules that bind to chemokines only bind weakly, making them poor drug candidates. Dr. Roth and a team of Burnham chemists are working to custom-design molecules that bind tightly to the chemokine, hoping to block its activity and stop the spread of tumors.
Choking Out Cancer
Ze'ev Ronai, Ph.D. is trying to kill off cancer by choking it. When tumors are deprived of oxygen, they activate a transcription factor called HIF-1a that helps the tumor compensate and survive. Inhibiting HIF-1a has been hypothesized to be a means of defeating cancer, as tumors eventually experience oxygen deprivation due to insufficient blood flow to the tumor. Dr. Ronai's laboratory has demonstrated proof of this concept by inhibiting PHD3, a regulator of HIF-1a. Binding of short protein fragments to PHD3 results in HIF-1a degradation and halts growth of metastatic tumors in mice. Dr. Ronai's team is now investigating how small molecule compounds might accomplish the same thing.
About Burnham Institute for Medical Research
Burnham Institute for Medical Research is dedicated to revealing the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Burnham, with operations in California and Florida, is one of the fastest growing research institutes in the country. The Institute ranks among the top four institutions nationally for National Institutes of Health (NIH) grant funding and among the top 25 organizations worldwide for its research impact. Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, infectious and inflammatory and childhood diseases. The Institute is also known for its world-class capabilities in stem cell research and drug discovery technologies. Burnham is a nonprofit, public benefit corporation. For more information, visit http://www.burnham.org.
Source: Josh Baxt
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