Research with real implications for improving the quality of life for injured veterans and active-duty soldiers
Gabriela Loots is a professor of orthopaedic surgery and the Doris Ellison Linn Chair in Bone Biology. Her research is focused on understanding how the human genome encodes important functional elements, and how proteins and regulatory DNA regions control the activation or repression of genes in different tissues and cell types under both healthy conditions and disease states.
Loots is the lead investigator on two new studies funded by the Department of Defense (DoD), which were profiled in a UC Davis story earlier this year. These studies take aim at bone loss in prostate cancer patients and prevention of post-traumatic osteoarthritis (PTOA), which are of special to military service members, who have double the rate of prostate cancer compared to civilians and face a higher risk of bone injuries.
One of the studies is on restoring bone density in patients being treated for prostate cancer. Loots’ team will use mouse models to study the restoration of bone density using an FDA-approved drug called romosozumab (Evenity), to see if it can prevent or slow the spread of cancer to the bones. Romosozumab is currently used to treat osteoporosis in women by stimulating new bone growth.
A major contributor to bone loss in prostate cancer patients is androgen deprivation therapy (ADT), which lowers testosterone levels but also weakens bones. Only a small fraction of men receiving this therapy undergo bone density screening, even though the risk of fracture and osteoporosis is high. This research could lead to a new approach in prostate cancer care — one that factors in bone health as a major contributor to cancer progression and uses bone-targeted therapies to protect patients from the deadliest stages of the disease.
The second federal grant is directed to the investigation of a little-known biological process (lactylation) that could help understand PTOA progression. The painful and often disabling condition commonly develops after joint injuries such as torn ACLs or menisci. Lactylation is a recently discovered biological process where lactate, a molecule from energy metabolism, attaches to proteins. This modification plays a crucial role in various cellular processes, including inflammation, embryonic development, and metabolism. Loots’ team is exploring how lactylation may be at least partly to blame for joint damage and arthritis pain following injury.
For the next two years, the team will examine whether blocking the production of lactate can reduce joint damage and pain. If lactylation is confirmed to be a key contributor, it could open the door to new therapies that prevent arthritis from developing after traumatic joint injuries.
Major Awards FY 2024-2025:
- Contribution of Bone Mass and Fracture to Bone Metastasis in Prostate Cancer
- Determine the Role of Histone Lactylation in Post-Traumatic Osteoarthritis and Arthritic Pain