Investigator Page

Tooraj Mirshahi, PhD

Staff Scientist

LOCATION

Weis Center for Research
100 North Academy Avenue
Danville, PA 17822
Phone: 570-271-5967
Fax: 570-271-6701
tmirshahi@geisinger.edu

EDUCATION

PhD, Virginia Commonwealth University, 1997
Postdoctoral Training, Mount Sinai School of Medicine, 1997-2004

RESEARCH FOCUS

Signal Transduction, Cellular Regulation, Neurosciences, Cardiovascular Sciences

EXPERTISE

Ion Channels, G Proteins, Phospholipids, Electrophysiology, Trafficking

RESEARCH INTERESTS

Regulation of Potassium Channels

Ion channels form a major class of membrane proteins and we are interested in their regulation and structure/function. We are particularly interested in potassium channels. These channels are implicated in cellular excitability. Kir3 channels for instance, regulate the resting membrane potential in atrial cells and reduce the heart rate in response to G proteins that are activated by muscarinic receptors upon vagus stimulation.
Our past work has focused on understanding the structural elements that mediate interactions between Kir3 channels and G proteins. We have mapped interaction sites between Gbg and the channels. Multiple interactions between the two serve distinct functional roles. For instance we have found mutants in Gb that eliminate functional interaction without affecting binding between the two proteins. We have identified sites on the channel that show preference for the Gbg that is released upon receptor activation as opposed to basal free Gbg. We are interested in understanding in detail how these interactions lead to channel activation and the molecular mechanism by which the channel gate is opened. We are also interested in finding the basis for the specificity that exists for signaling between G protein coupled receptors and potassium channels. Efforts in the lab are underway to determine where G proteins and potassium channels first interact and how they may regulate the stability and/or trafficking of one another.

Research Interest cont.

RECENT PUBLICATIONS

Wang, C., Mirshahi, U.L., Liu, B., Jia, Z., Mirshahi, T., Zhang, H.. (2008). Arachidonic acid activates Kir2.3 channels by strengthening channel-PIP₂ interactions.. Mol. Pharm., 73(4), 1185-1194.

Leung T.C., Humbert J., Stuaffer, A., Geiger K., Chen H., Tsai H.J., Wang C., Mirshahi T. and Robishaw J.. (2008). The orphan G protein-coupled receptor 161 is required for left-right patterning. Dev. Biol., in press.

Wheeler A., Wang C., Yang K., Fang K., Davis K., Styer A.M., Moreau C., Revilloud J., Vivaudou M., Liu S., Mirshahi T., and Chan K.W.. (2008). Co-assembly of different sulfonylurea receptor subtypes extends the phenotypic diversity of ATP-sensitive potassium (KATP) channels.. Mol. Pharm., in press.

Rusinova, R., Mirshahi, T., Logothetis, D.E.. (2007). Specificity of Gbeta/gamma signaling to Kir3 channels depends on the helical domain of pertussis toxin-sensitive Galpha subunits. J Biol Chem, 282, 34019-34030.

Michailidis, I.E., Helton, T.D., Petrou, V.I., Mirshahi, T., Ehler, M.D., Logothetis, D.E.. (2007). Phosphatidylinositol-4, 5-bisphophate regulates NMDA receptor activity through alpha-actinin.. J. Neurosci, 27, 5523-5532.