Postdoctoral researchers and Ph.D. candidates conduct the majority of the hands-on science at Sanford-Burnham. While principal investigators on the Sanford-Burnham faculty illuminate the paths research should take, it is the postdocs and graduate students who implement that vision. In return for their labor and insights, these young scientists learn by doing and receive critical insights from senior investigators. The experience they acquire will guide their future research.
Understanding Cellular Responses
Amy Chen is a Ph.D. candidate in U.C. San Diego’s Molecular Pathology program. Working in the Ronai lab, Chen seeks to understand the cellular response to endoplasmic reticulum (ER) stress. The ER is the cellular organelle responsible for protein folding. Since proteins derive their function from their shape, accurate folding is critical, and when that process malfunctions, the aberrant protein must be destroyed. Chen wants to know what happens to the cell cycle (the events associated with cell division) when misfolded proteins accumulate in the ER. Learning how cells respond to ER stress could lead to greater understanding of how cells cope with damage.
The Value of Spheroids
Postdoctoral researchers, like all scientists, ask questions and devise creative ways to answer them. Cancer researchers often ask whether a specific chemical will kill cancer cells, but finding the best ways to answer that question can be tricky. When a biologist studies cancer cells, he or she traditionally breaks the tumor apart and cultures the cells as a “monolayer” in a plastic dish. Unfortunately, this does not mimic a cancerous tumor in the body and its relationship to surrounding tissues. Solid tumors are exposed to a nutrient-rich, highly oxygenated environment on the outside and a nutrient-poor environment on the inside. When a drug is tested on a tumor, it may kill cells on the outside but not the inside.
A cancer spheroid
To solve this problem, Vuori laboratory postdoctoral fellow Amy Howes, Ph.D., among others at Sanford-Burnham, has been developing away to study cancer cells in three dimensions. Howes is working to create cancerspheroids—3D cell clusters that more closely resemble tumors in the body. With these spheroids, Howes may one day answer many questions about solid tumors, such as those seen in breast, brain, colon, prostate, lung and ovarian cancers.
Taking her work a step further, Howes has used the shared resources at the Conrad Prebys Center for Chemical Genomics to test hundreds of thousands of chemical compounds on solid tumor spheroids. She has found promising compounds that may one day lead to a new generation of cancer treatments.
Taking the Next Step
Masanobu Komatsu, Ph.D. has fond memories of his postdoctoral fellowship in the Ruoslahti laboratory.
“Dr. Ruoslahti has a Star Trek mentality about science: To boldly go where no one has gone before,” says Komatsu. “I think many of the Sanford-Burnham faculty who were mentored by him in the past received this frontier spirit from him, and I feel fortunate to be one of them because that’s what Sanford-Burnham science is really about.”
Komatsu has been an independent investigator for almost four years and has recently returned to Sanford-Burnham, at the Lake Nona campus, after working at the University of Alabama, Birmingham. An assistant professor in the Tumor Microenvironment program, Komatsu seeks to reverse abnormal vessel regeneration and restore normal functions in these vessels.
Researchers have known for some time that the gene VEG F stimulates blood vessel growth. But VEG F is only part of the story. In order to function properly, the vessels must mature.
“We need to understand the molecular mechanisms that lead to blood vessel maturation,” says Komatsu. “By understanding these processes, we can improve our ability to deliver chemotherapy to tumors, as well as treat symptoms of diabetes and eyesight deterioration.”
Blood vessels as seen through a confocal microscope