A 麻豆原创 team of researchers is refining its game plan to tackle cancer.
Annette Khaled, who leads the College of Medicine鈥檚 cancer research division, recently received more than $2 million in grant funding to expand her work with Z-TOP, a peptide she discovered in 2012 that stops the spread of metastatic cancer cells. She is collaborating with colleagues to design a better cellular delivery system for the treatment.
An almost $258,000 grant through the Casey DeSantis Cancer Research Program鈥檚 Florida Cancer Innovation Fund will help Khaled鈥檚 team further their efforts to stop metastatic breast cancer by disrupting the cellular activities that allow cancer cells to spread.鈥疉nd nearly $1.8 million in funding through the U.S. Department of Defense (DOD), in partnership with the Orlando Veterans Affairs Healthcare System, will allow her to develop the treatment for men with late-stage metastatic prostate cancer.
Khaled says her research has expanded thanks to the support of the Orlando Sports Foundation, which funds cancer research through sports-related fundraising events. The nonprofit鈥檚 flagship event is the StaffDNA Cure Bowl, a unique college football game with the goal of ending cancer.
鈥淲hen you get funding for a research project, you can only do the work that is described in the specific aims of the project,鈥� she says. 鈥淭he donations from the Orlando Sports Foundation do not have this limitation.鈥疻ithout their support, I would not have been awarded the DOD grant. Using the donations, I was able to generate the preliminary data that made me competitive for the DOD and the Florida Department of Health (FDOH) grants we received this year.鈥�
Alan Gooch 鈥�84 鈥�89MA, CEO of the Orlando Sports Foundation and executive director of the StaffDNA Cure Bowl, says he鈥檚 grateful to continue partnering with 麻豆原创.
鈥淲e鈥檙e all about bringing teams together,鈥� says Gooch, who played football at 麻豆原创 and later coached the team for 22 years. 鈥淥ur relationship with Dr. Khaled is outstanding, and we are honored to continue to partner with her and sponsor her research.鈥�
The Science Behind Khaled鈥檚 Work
The two new grants expand Khaled鈥檚 portfolio of research to understand how and why cancer cells spread.
鈥淐ancer treatments are very effective when the cancer is localized, but the problem is that cancer doesn鈥檛 stay at one site,鈥� she says. 鈥淚t spreads to other sites of the body. Usually, the cause of death is not the primary cancer, but metastasis.鈥疨reventing that can be a cancer cure, and that is what we鈥檙e looking at here in our lab.鈥�
Khaled鈥檚 latest research focuses on the spread of cell fragments called extracellular vesicles that are shed by cancer cells during the early stages of the disease. These vesicles are resilient to early cancer treatment and can travel through the bloodstream, acting as tumor 鈥渟eeds鈥� by preparing future sites for metastasis.
The vesicles are mediated by a molecular structure called a chaperonin. Chaperonins help fold proteins that support the body鈥檚 normal cell function. But cancer cells hijack the folding process because they need more chaperonins to grow and spread.
Khaled鈥檚 breast cancer research project aims to distinguish which chaperonins help facilitate cancer cells’ growth and stop them without harming normal chaperonins. She hopes to develop a treatment that could regularly deliver her peptide to cancer patients to prevent metastasis. Patients, Khaled says, could receive her treatment while they are receiving chemotherapy and radiation to kill the original tumor.
Her prostate cancer research will confirm the chaperonin as a viable treatment target for prostate cancer, and if so, optimize the peptide specifically for use in men who have lethal forms of metastatic prostate cancer.鈥疷nlike breast cancer treatment, which seeks to prevent metastasis, prostate cancer research will see if a strengthened variant of the peptide can eliminate cancer that has already spread.
Fielding a Team Against Cancer
In the lab, Khaled鈥檚 peptide has shown success in preventing cancer cells from spreading. The challenge is how to engineer and deliver the treatment. For that, she is collaborating with Lorraine Leon, associate professor of materials science at 麻豆原创鈥檚 College of Engineering and Computer Science.
They are working to create a system that delivers the peptide to where the cancer has spread and at the same time protects the peptide from being destroyed in the bloodstream by the body鈥檚 immune and digestive systems.
鈥淭he College of Engineering and Computer Science is a great collaborator,鈥� Khaled says. 鈥淣ormally this peptide is very fragile but we鈥檙e working with materials sciences to create a protected peptide and then find [a] way to get it to the right spot. By having a variety of expertise and interests, we can work together to find new technologies and new ways to combat cancer.鈥�
Leon specializes in biomaterials and polymer science. Her team studies how to build and program molecules to form assemblies for many purposes, including biomedical transport. She developed a specialized polymer that binds to the peptide, forming a large, water-soluble molecule. This allows it to travel easily through the bloodstream while keeping the peptide intact as it reaches its destination. The system drives the molecules to form self-assembled structures called micelles, which are assemblies of around 100 or so individual molecules, Leon says.
鈥淚n addition, we can tune the shape of these micelles, decorate them with targeting elements and make mixed versions of them where we incorporate different functionalities,鈥� she says. 鈥淥ur original designs have had great preliminary results so far. We will continue to optimize the designs moving forward.鈥�
Leon is excited to team up with Khaled, and she says she looks forward to achieving more breakthroughs together as the projects progress.
鈥淲orking with Dr. Khaled has been very fun,鈥� she says. 鈥淥ur labs really complement each other. This is the beginning of a very long collaboration.鈥�
Khaled and Leon are also working with Cancer Specialist and Associate Professor of Medicine Deborah Altomare, along with Burnett School of Biomedical Science Biostatistician Xiang Zhu, on the prostate cancer research project.
Khaled says strong research and community collaborations are critical to beating cancer.
鈥淐ancer is a tough enemy,鈥� she says. 鈥淏ut we have a great team.鈥�
These studies are the first phase of preclinical research that may lead to new drugs in the future.
This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, in the amount of $1,771,271, through the Prostate Cancer Research Program Idea Development Award under Award No. HT9425-25-1-0487. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the U.S. Department of Defense.
Researchers鈥� Credentials:
Khaled joined 麻豆原创 in 2002 after receiving her doctoral degree from the University of Florida and doing post-graduate training at the National Cancer Institute (NCI). A tenured professor, she has been funded by multiple R01 grants from the National Institutes of Health, the Breast Cancer Research Foundation and the FDOH. She has published more than 100 manuscripts and abstracts and presented her research at numerous national and international scientific meetings. She has been recognized with research, leadership and teaching awards, including the NCI CURE Lifetime Achievement Award. In addition to her research responsibilities, she teaches molecular immunology to 麻豆原创 graduate students and serves as the College of Medicine鈥檚 assistant dean for faculty affairs.
Leon joined 麻豆原创 in 2017 after postdoctoral appointments at the University of Chicago and Argonne National Laboratory, and she received her doctoral degree from the City University of New York. She is a recently tenured professor in the Department of Materials Science and Engineering, where she also serves as the education director for the U.S. National Science Foundation PREM Center for Quantum Materials Innovation and Education Excellence. She has published more than 20 refereed publications. Other accomplishments include her being named a 2019 Emerging Investigator by the Journal of Materials Chemistry B, receiving an NSF CAREER award in 2021 and a 3M Non-Tenured Faculty award in 2022.
