UCLA’s Christofk Lab’s may have clues to fighting cancer

Cancer is one of the leading causes of death in the United States. But do we know how it works? The UCLA Department of Molecular and Medical Pharmacology’s lab headed Dr. Heather Christofk, has identified the mechanism affecting the metabolism of cancer- and virus-infected cells, which may lead to a possible breakthrough in the fight against cancer.

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CAMPBELL: According to American Society of Clinical Oncology, cancer will surpass heart disease within the next 16 years to become the number one cause of death in the U.S. But how does cancer work? The Christofk Lab, a research lab staffed by university faculty and postdoctoral researchers in the UCLA Center for Health Sciences, has been studying cancer-infected cells.

CHRISTOFK: Our lab studies cancer metabolism. We’re very interested in how cancer cells achieve an altered metabolism compared to normal cells.

CAMPBELL: That was Professor Heather Christofk, head of the Christofk Lab, explaining the lab’s focus. According to Christofk, viruses may hold the key to understanding how cancer affects cell functions.

CHRISTOFK: We decided to use viruses as tools to study metabolic changes because we thought that might elucidate a mechanism important for these metabolic changes.

CAMPBELL: Like cancer, viruses can hijack a cell’s control center, causing it to cease all functions except reproducing and creating more virus-infected cells. The increased rate of reproduction raises the consumption rate of glucose, the cell’s main energy source. The lab believes that understanding how the virus takes over the cell’s function is key to understanding how to prevent that takeover. Contributing researcher Dr. Tom Graeber describes what the lab hoped to find.

GRAEBER: For this particular project, our hypothesis was that the metabolism would be changed by the virus, and we wanted to determine what was one of the major components of that change. Different types of viruses have different needs, so it does make some sense that a particular type of virus may have a different metabolic need and might co-opt a cell’s metabolism to best serve itself.

CAMPBELL: The lab succeeded in isolating the component causing the change in metabolic rate through experiments with adenoviruses, which are medium-sized viruses containing DNA. Professor Christofk explains:

CHRISTOFK: We used a series of deletion units, or versions of the virus that lack some of its DNA, and we found, through use of these deletion units, that there is a protein coding element, or gene, in the adenovirus genome that is necessary for this change in metabolism.

CAMPBELL: Postdoctoral researcher and lead author of the study Dr. Minh Thai was able to pinpoint the specific gene necessary for an adenovirus to cause increased glucose metabolism. Dr. Thai elaborates on his process.

THAI: (machine sounds in) Once we determined which protein was responsible for this metabolic phenotype, we were then able to go in and individually mutate different amino acids within this protein to find a version of the protein that no longer has this activity. (machine sounds out)

CAMPBELL: Dr. Thai was then able to use this protein to tease out the mechanism the virus uses to take over the cell’s machinery and propagate itself. Dr. Graeber believes isolating this mechanism can help with the development of new cancer-fighting drugs.

GRAEBER: For all kinds of human diseases, and including viral infections, you want to learn how does the diseased cell differ from a normal cell, with the hope that you can then design drugs that can target those differences.

CAMPBELL: Dr. Christofk believes the lab’s findings may have a profound effect on the development of these new drugs.

CHRISTOFK: Viruses are going to need to reprogram cells’ metabolisms in order to build more viruses. This is going to be a fundamental thing that I think we’re going to see across lots of different viruses and I think that they’re going to reprogram the metabolism in some common ways, and so there should be ways to block that, that are common across multiple types of viruses.

CAMPBELL: The lab hopes to apply its knowledge of viruses to the similar mechanisms employed by cancer cells. For now, it will use its findings to study more viruses and cancer cells in the hope of finding more clues in the fight against cancer. For Daily Bruin Radio, this is Chris Campbell.