Neil Harrison, PhD
Professor of Anesthesiology & Pharmacology
Dr. Harrison’s main area of research interest is in synaptic transmission, especially at inhibitory synapses, which are necessary for the normal processing of information in the mammalian brain. Failure of synaptic inhibition leads to epilepsy, while enhancement of synaptic inhibition is associated with reduced anxiety, muscle relaxation, sedation, hypnosis and anesthesia. The lab studies the details of inhibitory synaptic function, its modulation and plasticity, using a variety of modern electrophysiological and molecular biological techniques. Projects within the lab study these synapses at several different levels of organization, including brain slice, single cell and subcellular preparations. A major focus of the lab is on the GABA-A receptor, the principal receptor protein at inhibitory synapses in the brain. The lab personnel include physiologists, biophysicists, molecular biologists and pharmacologists.
Richard Levy, MD
Professor of Anesthesiology and Pediatrics at CUMC
Dr. Levy’s main area of interest is the adverse effect of environmental exposures on the developing brain. His lab is interested in developmental neuronal apoptosis, the neurotoxic effect of anesthetics, and the anti-apoptotic effects of carbon monoxide. He is currently evaluating the protective effect of subclinical carbon monoxide during anesthesia exposure. Dr. Levy is also interested in the gene- environment model of autism. He is currently evaluating the interaction between air pollution and Fragile X syndrome, the leading genetic cause of autism. The lab works with a number of mouse models, employs a variety of microscopy techniques, and commonly utilizes immunoblot analysis and subcellular fractionation to assess the mitochondrial apoptosis pathway.
Joachim Scholz, MD
Assistant Professor of Anesthesiology and Pharmacology, Columbia University College of Physicians and Surgeons
Area of Research - Peripheral neuropathy, pain
Special Focus -Cellular and molecular mechanisms of chronic pain
Pain serves an important protective function: it is a physiological response to harmful environmental or internal stimuli that alerts us of imminent tissue damage. However, in the presence of inflammation or repeated injury, pain no longer accurately reflects the nature or intensity of these stimuli. The sensation of pain increases and spreads beyond the injury site. Pain may even occur spontaneously, in the absence of a recognizable stimulus. Chronic back pain and pain associated with osteoarthritis are clinical examples of such inflammatory pain.
Neuropathic pain develops after a lesion or disease that directly affects the nervous system. Neuropathic pain has long been considered an exclusively neuronal “affair”. However, it is now clear that nerve lesions, too, provoke a marked inflammatory response that involves circulating and resident immune cells in the periphery and glial cell populations in the central nervous system. My laboratory is interested in identifying the molecular messages that neurons, immune cells and glia exchange with each other. We want to determine the signals that trigger recruitment and activation of immune and glial cells, and examine how signals released from immune and glial cells alter neuronal activity.
A key relay station for somatosensory information including pain is the dorsal horn of the spinal cord. Here, local interneurons and descending pathways from the brain jointly control the processing of afferent input. Nerve injury disrupts these control mechanisms profoundly. Using persistent neuropathic pain as a model of maladaptation in the nervous system, we study the impact of peripheral nerve lesions on the balance between excitatory and inhibitory regulation of synaptic transmission in the dorsal horn and the consequences for neuronal survival and function.
In an exciting new avenue of research, we are using stem cell technology to examine intrinsic risk factors for neurodegeneration and pain in diabetic neuropathy. The central idea behind this approach is to develop a model of neuropathy based on human induced pluripotent stem cells (iPSCs) that we derive from patients with type 2 diabetes. The phenotype of these patients has been carefully characterized to capture neuropathic deficits and differentiate between mechanistically distinct features of neuropathic pain. To generate neurons from iPSCs, we collaborate with colleagues in the Stem Cell Initiative at Columbia University and the Harvard Stem Cell Institute. Planned and ongoing research includes the differentiation and functional analysis of these neurons, the exploration of mechanisms responsible for peripheral neurodegeneration and pain, and the identification of potential targets for therapeutic intervention.
Robert A. Whittington, MD
Associate Professor of Anesthesiology
My current research interest primarily focuses on the impact of anesthesia and surgery on the neuropathogenesis of Alzheimer’s disease (AD). Using transgenic mouse and cellular models of AD, my laboratory is investigating the impact of prolonged anesthesia exposure on the development of tau protein-related neurofibrillary pathology, one of the neuropathological hallmarks of Alzheimer’s. The long-term goal of this research is to better understand how anesthesia and surgery modulate AD-related neuropathogenic pathways in order to identify perioperative treatment strategies that preserve cognitive function in those patients who are at risk for postoperative cognitive decline as well as incident dementia.