Neuroimmunology; Behavioral pharmacology; Gene therapy; Immunology; Molecular and Cellular Biology; Molecular Basis of Disease; Neurobiology; Gene Expression; Signal Transduction; Protein Function and Structure; Neuropharmacology
My research spans three interrelated fields: chronic pain, depression and inflammation. Experiments in my laboratory focus on how brain-derived pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF), function as modulators of brain-body interactions during neuropathic pain and how brain-TNF is involved in the mechanism of action of antidepressant drugs. My overall goal is to advance knowledge of, and therapeutic efficacy for pain, depression, neuro-inflammation and drug addiction. This research is based on my earlier work showing that neurons produce the pro-inflammatory cytokine TNF and that the production of TNF by macrophages is regulated by neurotransmitters. Cytokines and neurotransmitters are principal signaling molecules that mediate bidirectional communication between the nervous and immune systems--the crosstalk important in maintaining homeostasis. Consequently, aberrant production of either of these two classes of mediators could profoundly affect signaling by the other, thereby impacting health. A shift in balanced cytokine-neuron interactions that regulate neurotransmitter release in the central nervous system (CNS), and that have potential behavioral consequences, manifest themselves as states of depression and chronic pain. My research uses both cell systems and animal models to test these hypotheses. Colleagues and I use a combination of imaging techniques to localize cytokine production, bioassays and ELISA (enzyme-linked immunosorbent assays) for pharmacological and functional analyses, electrophysiological (brain slice stimulation) and molecular methods for our studies. In addition to investigating neuron functioning in the brain, trainees in my laboratory also study the peripheral macrophage, a major source of TNF during inflammation. Specifically studying neurotransmitter regulation of TNF production in the periphery is enhancing our knowledge of how the brain controls a peripheral inflammatory lesion. Our studies are designed to investigate the mechanisms of centrally mediated pain as associated with immune dysfunction and to elucidate mechanisms of drugs used to treat such pain states. My projects are evolving to investigate the mechanisms and neural pathways involved in TNF neuromodulator functions during chronic pain (due to peripheral nerve injury and diabetes) and stress-induced depressive behavior. We also study mechanisms contributing to the comorbidity of chronic pain and depression. I collaborate with researchers in several UB departments and at other institutions. Our projects include using noninvasive methods for delivery of anti-TNF therapeutics for chronic pain, elucidating the neural-immune mechanisms involved in the rapid recovery afforded by centrally administered anti-TNF therapy and using nanotechnology-mediated, targeted gene silencing within the CNS. I am invested in helping my undergraduate and graduate students, medical residents and postdoctoral fellows realize their potential and achieve their goals. Previous students have advanced professionally and hold clinical, academic and industrial positions.