Dendritic Spines: Old News, New Applications

Abstract

My research interests focus on spinal cord injury (SCI) pathology, particularly mechanisms underlying neuropathic pain and spastic movement disorders. My long-term goal is to identify and assess novel targets and strategies that can help restore normal function after SCI. My hope is that our efforts will eventually lead to more effective and safe clinical therapies.

As the Principal Investigator (PI) of US Federal awards and privately funded grants, I have applied my expertise toward managing the execution of a broad range of projects, and have developed strong collaborations with domestic and international teams. As an Associate Director of the Center for Neuroscience and Regeneration Research at the West Haven VA Medical Center, I currently supervise a wonderful team of students, postdocs, and junior faculty in our SCI/D research program. Our published research has utilized in vitro and in vivo approaches, including a combination of anatomical analyses, behavioral assessment, viral-based gene therapy, and whole-animal electrophysiological techniques.

Over the past decade, my team has laid the groundwork demonstrating that maladaptive dendritic spine remodeling within nociceptive or motor reflex circuits underlies SCI-induced hyperexcitability disorders, i.e., neuropathic pain and spasticity. This body of work has also demonstrated for the first time that the Rac1-PAK1 pathway is a key mechanism involved in maintaining chronic pain and spinal motor reflex dysfunction. A core implication of these insights is that dendritic spine profiles may serve as a morphological correlate for sensory-motor hyperexcitability disorders, and could be used to predict therapeutic-drug response. Recently, we pioneered the use of long-term, in vivo two-photon imaging assays that we now use to investigate the relationship between dendritic spine dynamics in the spinal dorsal horn and neuropathic pain.