SUMMARY
The research of Davide Povero, Ph.D., M.B.A., focuses on interpreting metabolic changes that influence chronic liver condition development and cell death escape in biliary cancer. These metabolic changes occur because of metabolic reprogramming or cancer mutations. Dr. Povero's goal is to identify new treatment strategies that target cancer metabolic vulnerabilities and help reestablish metabolic homeostasis in the liver.
Dr. Povero's research team is particularly interested in metabolic reprogramming caused by loss-of-function mutations resulting in escape from ferroptosis, an unusual iron-dependent mode of cell death driven by phospholipid peroxidation. Identifying such mechanisms may lead to new treatments that target other forms of cell death and help manage cancers that do not respond to current cytotoxic therapies.
Additionally, Dr. Povero is interested in solving the mechanisms of lipid metabolism alterations that drive the development of metabolic dysfunction-associated steatotic liver disease. He strives to find these mechanisms by using multi-omics strategies and leveraging unusual conditions, such as microgravity.
Focus areas
- Ferroptosis in biliary cancer. Dr. Povero's current work identifies metabolic adaptations driven by BAP1 loss-of-function mutations. These changes result in resistance to ferroptosis in cholangiocarcinoma. To find these adaptations, he uses many in vitro and in vivo gene editing strategies, biochemical and functional assays, and genetically encoded biosensors. Dr. Povero also investigates key protein liquid-liquid phase separation as a mechanism to better regulate ferroptosis.
- Pyrimidine and lipid metabolism in metabolic dysfunction-associated steatotic liver disease. Dr. Povero studies the mechanisms underlying the relationship between uridine homeostasis and fat storage in hepatocytes, a hallmark of metabolic dysfunction-associated steatotic liver disease and its progressive form, metabolic dysfunction-associated steatohepatitis. To address this goal, he leverages experimental multi-omics data generated in microgravity and conducts in vitro and in vivo biological validations.
- New small interfering RNA-based nanotherapeutics triggering ferroptosis. Dr. Povero focuses on developing and validating new siRNA-based nanoparticles coated with aptamers and specifically targeting cholangiocarcinoma cells to induce ferroptosis as a new treatment strategy to improve cytotoxic therapy and immunotherapy.
- Ferroptosis and the tumor immune microenvironment. Dr. Povero explores the role of ferroptosis in regulating a tumor immune response. He explores the immunosuppressive and immunogenic roles of ferroptotic cancer cells. Dr. Povero is interested in the immunoregulatory role of lipid mediators and oxidized lipids released because of ferroptosis in the tumor immune microenvironment.
Significance to patient care
Dr. Povero researches better patient care by advancing treatment options for liver disease and biliary cancers. He believes that understanding how certain mutations make cancer cells resistant to ferroptosis, a type of cell death, can help create new treatments that target cancer cell weaknesses.
These new treatments may be more effective for patients with cholangiocarcinoma.
Dr. Povero studies how liver cells store fat, and this may lead to new treatments for liver disease, thus improving the lives of patients with conditions such as steatotic liver disease.
Dr. Povero develops new nanoparticles to specifically target cancer cells that could make treatment for liver cancer more precise and reduce side effects. By exploring how ferroptosis affects the immune system, Dr. Povero may uncover ways to enhance immunotherapy. Improving immunotherapy may help the body fight cancer more effectively.
Professional highlights
- Member, editorial board, Hepatology, 2024-present.
- Member, editorial board, JHEP Reports, 2024-present.
- American Association for the Study of Liver Diseases:
- Member, 2013-present.
- Pinnacle Research Award in Liver Diseases, 2024.
- Secretary, Liver Cancer Special Interest Group Steering Committee, 2021-2023.
- Member, European Association for the Study of the Liver, 2011-present.
- Research fellowship, Cholangiocarcinoma Foundation, 2024.
- Roger L. Jenkins Postdoctoral Research Award, American Liver Foundation, 2014.