Miller Photo


Molecular
pharmacology of
receptors, signal
transduction and
synaptic
transmission.
Regulation of
neuronal receptors
and ion channels.
Molecular aspects of
nerve cell
degeneration.






   Richard Miller
Office Lurie 8-125 (312) 503-3211
Lab Lurie 8-250 (312) 503-3221

r-miller10@northwestern.edu

Research in out laboratory is concerned with understanding molecular aspects of synaptic communication under normal circumstances and also under pathological conditions. For example, for several years we have studied the voltage sensitive Ca channels that are responsible for the influx of Ca into neurons and the release of transmitter. We have demonstrated that Ca channels consist of a family of related molecules that form multisubunit channels. Each type of channel has different biophysical and pharmacological properties and different neuronal functions. We study these molecules using molecular biological, electrophysiological and imaging techniques. Recently we have also started to generate mice in which different types of Ca channels have been knocked out and these have been very useful in our efforts to define channel function. We are currently examining the properties of a new type of channel that we have recently cloned and which appears to be highly expressed in the nervous system.

Ca channels can also be regulated through the activation of G-proteins and we have also studied this process. Activation of different types of G-protein coupled receptors expressed by neurons can be shown to have a variety of consequences for neuronal function ranging from the rapid control of ion channels and neuronal excitability to long range effects on neuronal survival. We have been using FRET based imaging and other paradigms to examine the regulation of G-protein subunits by receptors and other molecules in neurons.

Several projects in our laboratory are also concerned with understanding the processes that cause neuronal degeneration. Increases in Ca and associated changes in mitochondrial function are clearly important. We have been particularly interested in the molecular basis of neuronal dysfunction observed in association with infection by the HIV-1 virus. We have been examining the role of chemokine receptors in this phenomenon, and have found that receptors for chemokines are widely expressed in nervous system and seem to have a variety of functions. For example ,we have used mice in which the CXCR4 chemokine receptor has been knocked out to show how this receptor is involved in the development of the dentate gyrus of the hippocampus. Other studies are involved in trying to define how the HIV-1 virus utilizes chemokine receptors in the nervous system to produce neuronal dysfunction in AIDS.

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