Award: Psoriatic Arthritis Research Grant
Biography: Dr. Sakeen Kashem is a physician-scientist with training in dermatology, immunology, and pain neuroscience. His research focuses on the neuroimmune mechanisms driving psoriatic arthritis (PsA), a chronic inflammatory disease with prominent skin, joint, and pain manifestations. The sensory nervous system plays an active role in psoriatic disease – a striking clinical observation is that psoriatic plaques resolve following peripheral nerve injury or denervation, demonstrating that ongoing sensory input is required to sustain skin inflammation.
Building on this, Dr. Kashem’s work asks how sensory neurons are pathologically altered in PsA and whether the neuronal subsets that drive pain operate through mechanisms shared with or distinct from those sustaining neurogenic inflammation. This distinction has direct therapeutic implications: convergent mechanisms would allow a single intervention to address both pain and inflammation, while divergent mechanisms would demand separate strategies. By combining clinical access to PsA patients with mechanistic studies, he aims to identify neuroimmune targets for a disease where pain remains poorly treated.
Research Summary: Psoriatic arthritis (PsA) is a chronic inflammatory disease that causes joint damage, skin inflammation, and pain. While current treatments can reduce inflammation, many patients continue to suffer from persistent pain. Recent scientific advances show that sensory nerves, which normally detect pain, can also actively worsen inflammation. However, which nerves are involved in PsA and how they communicate with the immune system remain unknown.
Our early studies in mouse models of PsA show that removing a specific group of pain sensing nerves greatly reduces both pain and inflammation in the skin and joints. These benefits are accompanied by a decrease in inflammatory immune cells that are known to drive PsA. We also discovered that these sensory nerves increase production of a factors that supports inflammatory immune cells and has been linked to both arthritis and pain. These findings suggest that certain sensory nerves may actively promote PsA by signaling to the immune system.
In this project, we will first identify the exact sensory nerve subtype responsible for driving pain and inflammation in PsA. Using advanced single-cell technologies, we will map which neuronal populations are activated during disease and test their function using targeted genetic tools. Next, we will determine how these nerves communicate with immune cells, focusing on finding the neuronal signals required to sustain inflammation and pain.
By uncovering how sensory nerves contribute to PsA, this research aims to identify new treatment strategies that target both pain and inflammation together. These discoveries could lead to therapies that provide more complete and lasting relief for patients living with psoriatic arthritis.