The Ed and Ethel Moore Alzheimer鈥檚 Disease Research Program, which aims to improve the health of Floridians by researching treatments for Alzheimer鈥檚, recently awarded Jihe Zhao $350,000 to better understand the molecular changes that cause the disease. Alzheimer鈥檚 affects some 6 million Americans including about 600,000 Floridians.

Zhao, a cancer researcher at the Burnett School of Biomedical Sciences, has focused much of his research into developing new targets for effective anticancer therapy and has now expanded his research to include Alzheimer鈥檚 disease.

Historically, Alzheimer鈥檚 research has focused on plaques and tangles of proteins that form in the brain cells of Alzheimer鈥檚 patients. And much of that work has focused on reducing these blockages. However, therapies based on reducing plaque have not been effective.

Zhao is taking a different approach, investigating the molecular causes of changes in the brain that lead to Alzheimer鈥檚.

鈥淚dentifying the molecular causes and mechanisms behind the disease is the first step to developing effective therapies,鈥� he said. 聽His research will focus on KLF8 (Kruppel-like factor 8) 鈥� a protein important for brain function that has been recorded as deficient in patients with Alzheimer鈥檚. 鈥淏ut how this deficiency contributes to the development of Alzheimer鈥檚 disease has never before been investigated due to the lack of proper animal models,鈥� Zhao says. 鈥淪o this is the very first study of its kind.鈥�

Zhao鈥檚 lab has developed novel mouse models in which the amount of KLF8 protein in neurons can be altered to see how reduced levels impact the brain and development of Alzheimer鈥檚. He says preliminary evidence shows a KLF8 deficiency causes neurons to die and that changes in the protein impact genes critical for maintaining cognitive function and a normal brain environment.

鈥淭hese results strongly suggest that KLF8 plays a role in protecting neurons and that loss of KLF8 function may be a molecular cause of Alzheimer鈥檚 disease,鈥� Zhao says, adding that the findings of this study will be critical to advancing knowledge of how Alzheimer鈥檚 develops and provide new targets for therapy.

The study could also open doors for earlier diagnosis and possible prevention of the disease.

In the U.S. alone, the annual cost of providing care to Alzheimer鈥檚 patients was estimated at $320 billion in 2022 and this number is expected to increase if more effective therapies are not discovered.

鈥淪o it is urgent to better understand the disease mechanisms so we can diagnose it earlier and create more effective treatment to save lives and reduce the burden on the nation鈥檚 healthcare,鈥� Zhao says.

Zhao received his MD at the Chinese Medical University and a Ph.D. at Tohoku University (Japan). He completed postdoctoral training at Cornell University.

The medical school has a team of 鈥淐ancer Assassins鈥� 鈥� researchers in the Burnett School of Biomedical Science who are using their scientific expertise to find a cure:

Dr. Annette Khaled

Khaled chairs the College of Medicine鈥檚 Cancer Research Division. She is using nanoparticles to track down and kill metastatic breast cancer cells. These cells, which spread from the original tumor, cause cancer to recur and spread into the brain, blood and lungs 鈥� causing death to most patients. Khaled鈥檚 technology is expected to begin clinical trials in 2018.

Dr. Deborah A. Altomare

Altomare is finding new ways to fight pancreatic and ovarian cancer by studying how cancer tumors interact with surrounding cells. She is working to develop targeted drugs and immune cell therapy to block the growth and spread of cancer tumors.

Dr. Claudia Andl

Andl creates a cancer tumor鈥檚 environment in a test tube to better understand how tumor cells interact with their environment and spread. With that focus, she is looking to develop better treatments for oral and esophageal cancers.

Dr. Karl X. Chai

Chai鈥檚 research focuses on HER2+ breast cancer 鈥� an especially aggressive form that hits about 1 in 5 breast cancer patients. This type of cancer is hard to fight because the breast cancer cells have a particular protein that causes them to grow and spread quickly. Chai is looking at the novel mechanisms in these cells and what makes them resistant to Herceptin, the drug approved for treatment.

Dr. Ratna Chakrabarti

Chakrabarti is studying the cellular differences between aggressive and more inactive cancers to better identify patients who have a genetic predisposition to develop drug-resistant prostate cancer. By identifying the genetic and epigenetic components of prostate cancer, Chakrabarti hopes to develop better therapies for prostate cancer patients and improve their quality of life. Her lab is also conducting screenings of synthetic compounds that may prove to be novel anti-cancer agents.

Dr. Li-Mei Chen

Chen is identifying the novel mechanisms in lung cancer cells that make them resistant to chemotherapies. Lung cancer is the second-most-common cancer in men and women and is by far the leading cause of cancer deaths. About 1 in 4 cancer deaths are from lung cancer 鈥� more than colon, breast and prostate cancer combined.

Dr. Alicja Copik

Copik is developing ways to activate the body鈥檚 Natural Killer cells to kill cancer. NK cells are a veritable army that identify and attack invaders like cancer and viruses. She has developed a technology that uses nanoparticles to activate and grow NK cells to fight cancer. The therapy will begin clinical trials in 2017 and shows promise in treating leukemia and other cancers.

Dr. Jihe Zhao

Zhao鈥檚 question: Why does the heart rarely get cancer? He is looking to understand why cancer spreads to some organs like the brain and not others like the heart. Dr. Zhao is also discovering how to protect the heart from damage caused by anti-cancer therapies.

Learn more about the medical school鈥檚 cancer division at ,

The protein, KLF8, appears to protect tumor cells from drugs aimed at killing them and even aid the tumor cells鈥� ability to regenerate.

鈥淎ll cells have a DNA-repair mechanism,鈥� explained Jihe Zhao, a medical doctor and researcher who in the past few months has published several articles related to the protein in the Journal of Biological Chemistry and , among others. 鈥淭hat鈥檚 why we survive constant DNA damage threats. But KLF8 is overexpressed in specific cancers, such as breast cancer and ovarian cancer. The thought is that if we can stop it from switching on, we may be able to stop the tumors from coming back as part of therapy. We still need to do a lot more research, but it is plausible.

There are between 2.5 million and 2.7 million women who have breast cancer in the United States and 10 to 20 percent will experience a recurrence, according to the American Cancer Society. Current treatment options, depending on the stage of cancer, include surgical removal followed by chemotherapy using a combination of cancer killing drugs. Each year about 22,200 women are also diagnosed with ovarian cancer.

DNA damage-based chemotherapies depend on failure of cancer cells to repair the DNA damage and subsequent cell death, according to the journal article. Aberrant high levels of DNA repair function in the cells likely increase not only the resistance of the cells to such therapies but also the malignancy of the cells due to improper DNA repair-mediated genomic and chromosomal instability.

In the study, Zhao鈥檚 team tested one specific cancer-fighting drug used in the treatment of breast cancer to determine the role of the protein.

鈥淚ndeed, our results have clearly linked the KLF8-promoted DNA repair to the cell resistance to doxorubicin-induced cell death,鈥� Zhao said. 鈥淚t remains to be determined whether KLF8 plays a similar role in repairing DNA damage caused by other types of genotoxic agents such as DNA alkylating agents and ionizing radiation.鈥�

Even so, the results suggest that in addition to enhancing the drug resistance of the cancer cells, KLF8 could play a role in disturbing genomic integrity through its aberrant DNA repair function and subsequently contribute to aggressive progression of cancer.

Zhao, an associate professor, moved his team to 麻豆原创鈥檚 Burnett School of Biomedical Sciences at the College of Medicine in 2010. In 2002 he started his own la at Albany Medical College and before that he spent six years in post-doctoral training in Cornell University, 聽Ithaca, N.Y.聽 He earned his M.D. from Chinese Medical University, Shenyang, China, and Ph.D. in cancer cell biology from Tohoku University Faculty of Medicine, Sendai, Japan. He sits on the editorial boards of several peer-reviewed journals related to cancer research and reviews research articles for many prestigious journals including Cancer Research, Oncogene, Molecular Cell, Nanomedicine, and Journal of Biological Chemistry, to name a few. His research programs are funded by National Cancer Institute of National Institute of Health, American Cancer Society, Susan Komen for the Cure Breast Cancer Foundation, and others.