Above photo: Cancer researcher Aaron Jacobs (far right) stands with his lab team, (l-r) Buddhini Samarasinghe, PhD, postdoctoral fellow; Christina Wales, research assistant; Nalini Yadav, PhD student; and Rachel Gristock, Kea‘au High School student. 2012
Associate Professor Jacobs researches the role of cell stress in the progression of cancer, notably the role of the transcription factor HSF1 in cancer. His goal is to identify HSF1-regulated genes and evaluate their significance in human disease.
Aaron Jacobs, associate professor of pharmaceutical sciences at the University of Hawai‘i at Hilo Daniel K. Inouye College of Pharmacy, is doing research into the role that cell stress plays in the progression of cancer. He also teaches integrated therapeutics and emerging topics in drug discovery, including lectures on infectious diseases, anticancer drugs, and endocrine agents.
Jacobs’s research focuses on the role of the transcription factor HSF1 in cancer. HSF1 regulates gene expression in response to heat shock, drugs, and endogenous metabolites, and it controls the levels of several hundred genes.
“Our goal is to identify HSF1-regulated genes and evaluate their significance in human disease,” says Jacobs. “Our primary interest is in the study of colorectal and breast cancers. Some of the processes affected by HSF1 that we are investigating are cell death, cell division, inflammatory signaling, and chemoprevention.”
Although Jacobs mainly studies colon and breast cancer, much of his work is applicable to other cancers as well.
“There are various types of stress that a cancer cell commonly encounters, such as low oxygen and nutrient levels, exposure to damaging chemicals, as well as heat and radiation, typically as a consequence of cancer therapy,” he says. “We found that cancer cells can defend themselves against stress by increasing the levels of a protein called BAG3. This protein helps to protect the cancer cells from dying when they encounter stress, and is one of the reasons that cancer is both aggressive and resistant to treatment.”
Jacobs’s projects are on the role of HSF1-dependent gene expression in autophagy, impact of HSF1 on polyamine biosynthesis, regulation of HSF1 activity by FDA-approved drugs, and the effect of endogenous oxidized lipids on inflammatory signaling in breast cancer. His research funding is from the National Institutes of Health.
Jacobs says the most surprising find in his work is that the human body makes its own chemicals which can cause cell stress and drive cancer. He says it is well known that chronic inflammation can promote certain types of cancer. During inflammation, lipids (fats) generate highly reactive compounds called electrophiles.
“These electrophiles can be perceived as a type of cell stress called heat shock which causes cancer cells to bolster their defenses, in part by increasing their levels of BAG3,” he says. “By reducing chronic inflammation and lipid oxidation in the body, we might reduce the risk for cancer.”
Jacobs and his lab team are also looking into something called “drug re-purposing” that can see more rapid results.
“We have already examined about 1,000 known drugs used to treat everything from diabetes to toenail fungus,” he says. “We know that if you can block the ability of cancer cells to bolster their defenses, then anti-cancer treatments are more effective.”
Among the drugs tested in Jacob’s lab, a select few have been found that can block heat shock and reduce BAG3 levels in cancer cells.
“We are now in the process of testing these drugs in our laboratory to see if they can, in fact, improve the response to cancer therapy,” Jacobs says.
Academic research is critical in the fight against cancer. It generates novel insights that can eventually lead to new or improved treatments. Sometimes this can take several years to happen.
“By understanding the basic processes that drive cancer, we hope to find ways to enhance both prevention and treatment,” says Jacobs.
Education and accolades
Jacobs received his doctor of philosophy in pharmacology from the University of California at Los Angeles. He was awarded the 2010 College of Pharmacy Teacher of the Year, elected by the class of 2011, and the 2012 College of Pharmacy Teacher of the Year, elected by the class of 2014, UH Hilo.
By Susan Enright, public information specialist, Office of the Chancellor.
Published Oct. 17, 2012; latest update May 11, 2018.