The University of Texas MD Anderson Cancer Center
Department of Symptom Research
Our studies aim at increasing our understanding of the pathophysiology of cancer therapy-induced neurobehavioral toxicity, including neuropathic pain, and cognitive dysfunction (chemobrain). This is important because neurobehavioral deficits as a result of cancer treatment greatly affect patient comfort and functioning, and may lead to lower doses of therapy, treatment holds, and even treatment termination, thus potentially influencing patient survival. The underlying mechanisms of behavioral toxicity are poorly understood and this is required for development of preventative and curative interventions.
Specific projects include an RO1-funded study on A novel neuroimmune mechanism underlying comorbid depression and neuropathic pain. We use behavioral and immune measures in various KO mouse strains to test the hypothesis that reduced microglial GRK2 caused by the neuroinflammatory response to cancer-therapy increases p38 activity, pro-inflammatory cytokine production and IDO expression, thereby promoting development of neuropathic pain, depressive-like behavior and other neurobehavioral symptoms.
A second RO1- funded study focusses on A novel molecular switch regulating transition from acute to chronic pain. This project is based on our recent discovery that GRK2 in sensory neurons is an important regulator of the pain response. GRK2 regulates cAMP signaling to Epac and its target PKCepsilon. Using behavioral, molecular and biochemical approaches we now aim at understanding how GRK2 regulates cAMP to EPAC signaling to promote transition to chronic pain.
Additional studies focus on the role of infiltrating immune cells in chemotherapy-induced neuropathic pain and on the mechanisms underlying chemobrain and the potential to treat brain damage by nasal administration of mesenchymal stem cells.
Education & Training
Ph.D. - Utrecht University - 1990