About This Project

Ask the Scientists

What is the context of this research?

The laboratory at USF Morsani College of Medicine is growing in space, personnel and research interests. Our Department of Molecular Pharmacology and Physiology has a faculty base with a broad range of expertise and backgrounds. The main focus of our laboratory is to further expand on the development and application of metabolic therapies for the treatment of seizure disorders, metabolic disorders, neurodegenerative diseases, wound healing and cancer. We now have four full time PhD students, a laboratory manager, a postdoctoral fellow and several highly motivated undergraduate and pre-medical students working in the laboratory.
Each member has a primary project, but they all work as a Team to support the efforts of others by collecting data, discussing the results and presenting the information to the public. Our laboratory is equipped with a variety of equipment to assess the efficacy of metabolic therapies on neurological function, motor function and metabolism, which are all linked to clinical assessment in patients.
Collaboration is a very important and necessary part of forming a team
of expertise to optimize the use of resources for scientific discovery. We maintain collaborations with a number of institutions including Boston College, Case Western University, The University of Texas Southwestern Medical Center and the University on Tampa to name a few.
Dr. D'Agostino is an Assistant Professor at the University of South
Florida College Of Medicine, Molecular Pharmacology & Physiology where he develops and tests metabolic therapies, including alternative energy substrates and ketogenic agents for neurological disorders, cancer and wound healing. While studying the effects of gasses on the brains of Navy Seal divers, he developed an approach for metabolically starving cancer cells through diet and compressed oxygen, replacing chemotherapy, surgery, or radiation.

What is the significance of this project?

This project has the potential to impact how we treat cancer patients in the future. It could affect individuals who have metastatic cancer and potentially other cancer types as well. Metastatic cancer solely means that the cancer that started in a certain region has spread throughout the body. The problem is that the accepted standard care for those with metastatic cancer consists of
cytotoxic chemotherapy and radiation often does more harm than good to the cancer patient. Metabolic therapies like the restricted ketogenic diet exploit the
theory that cancer is a metabolic disease. Most cancers result from environmental and lifestyle factors that promote cellular stress and progressive mitochondrial damage. Mitochondrial damage impairs energy metabolism. The fidelity of the genome is tightly correlated with stable energy (ATP) generation from the mitochondria, and failure to maintain cellular energy triggers the activation of cancer genes. The ketogenic diet can be used as a stand-alone therapy or combined with other therapies like hyperbaric oxygen or cancer-specific metabolic inhibitors. A ketogenic diet calls for eliminating all but non-starchy vegetable carbohydrates, and replacing them with high amounts of healthy fats and low to moderate amounts of high-quality protein. The premise is that since cancer cells need glucose to thrive, and carbohydrates turn into glucose in your body, then lowering the glucose level in your blood through carb and protein restriction literally starves the cancer cells to death. Additionally, low protein intake tends to minimize the mTOR pathway that accelerates cell proliferation and lowers the amount of one particular amino acid, glutamine, which is also known to drive certain cancers.

Therapeutic ketosis and hyperbaric oxygen offer a nontoxic approach to
cancer management, especially when combined. Therapeutic ketosis can be achieved with a ketogenic diet and ketone supplements (ketone ester or ketone salts) and this makes it possible to achieved sustained hypoglycemia because the ketones function as an alternative fuel source. Normal health cells readily adapt to using fatty acids and ketone bodies for fuel, but cancer cells lack this metabolic flexibility. Nontoxic metabolic therapies and hyperbaric oxygen therapy exploits the overlapping metabolic and oxidative vulnerability of cancer cells. Our laboratory is focused on validating this approach to cancer management in pre-clinical studies and moving these nontoxic therapies into the clinic.

What are the goals of the project?

Currently, the only treatment for metastatic cancer is radiation and chemotherapy, which can lead to very expensive hospital bills. Our objective is to find which levels of hyperbaric oxygen provide the mice with the lowest amount of oxygen along with the most positive results in regards to reducing the size of their tumors. If we had the funds to run trial experiments on the mice to figure out the lowest percentage of oxygen they need to help them become healthier, we could then potentially be able to translate these studies to human clinical trials. In the future we hope to be able to provide cancer patients with this information so that if they choose not to go through chemotherapy or radiation, they will be able to at least use hyperbaric oxygen treatment as an alternative or even in addition to other cancer treatment.