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Laura Conforti, PhD
Associate Professor
laura.conforti@uc.edu
Primary Appointment: Division of Nephrology & Hypertension, Department of Internal Medicine
My laboratory is interested in ion channels and the membrane mechanisms that regulate the activation and function of T lymphocytes. Ion channels, located on the membrane of T cells, are the effectors which link antigen recognition to T cell function and gene regulation by controlling calcium homeostasis.
Our main focus areas are:
1. Role of ion channels in T cell response and adaptation to hypoxia. Hypoxia (low oxygen availability) can occur in physiological conditions in the lymph nodes and spleen as well as pathological conditions such as wounds and solid tumors. Therefore, T lymphocytes encounter hypoxic environments during their maturation process as well as in pathological sites where they fight diseases. Our group recently demonstrated that hypoxia inhibits the potassium channel Kv1.3 and effectively blocks T cell activation i.e. T cells are no longer able to combat the disease at hand. This may contribute to the failure of the immune system to fight cancer cells.
2. Role of ion channels in the development and persistence of chronic autoimmune diseases such as systemic lupus erythematosus (SLE). SLE affects about 1.5 million Americans, predominantly women, and is characterized by a broad variety of clinical symptoms such as glomerulonephritis and central nervous system impairment. We have shown that human T lymphocytes present with a characteristic defect in potassium channel behavior. This finding opens the possibility of targeting ion channels for new therapeutic intervention.
3. Membrane mechanisms involved in the early phases of the T cell activation process. The response of T lymphocytes to antigens occurs through the physical interaction with antigen presenting cells and the formation of a specific contact area between these cells called immunological synapse. Functionally the immunological synapse is important for the proper development of the T cell response. We are interested in studying the processes by which ion channels move into this special area and the functional consequences of this localization.
The techniques used in the laboratory include, but are not limited to, electrophysiology (patch clamp) and fluorescence and confocal microscopy. Furthermore, novel high throughput experimental methods using MEMS (microelectromechanical systems) and nanotechnology are currently applied, which allow the development of systems biology models for T cell activation.
More Information
In the news: (5-26-2009)
Open PostDoc position. Please contact: laura.conforti@uc.edu |
Publications, Selected:
Conforti L., Petrovic M., Mohammad D., Lee S., Ma Q., Barone S. and Filipovich A. H.: Hypoxia regulates expression and activity of Kv1.3 channels in T lymphocytes: a possible role in T cell proliferation. J. Immunol. 170: 695-702, 2003.
Robbins J.R., Lee S.M. , Filipovich A.H., Neumeier L., Szigligeti P., Petrovic M. and Conforti L. :Hypoxia modulates early events in T cell receptor-mediated activation in human T lymphocytes via Kv1.3 channels. J. Physiol, 564.1: 131-143, 2005.
Nicolaou S., Neumeier L., Peng YQ, Devor D. and Conforti L. :The Ca2+-activated K channel KCa3.1 compartmentalizes in the immunological synapse of human T lymphocytes. Am. J. Physiol. - Cell Physiol. 292(4): C1431-1439, 2007.
Nicolaou S., Szigligeti P., Duncan H., Neumeier L., Molleran Lee S., A.B. Mongey, Kant S. K., Filipovich A. H. and L. Conforti: Altered dynamics of Kv1.3 channel compartmentalization in the immunological synapse in Systemic Lupus Erythematosus. J. Immunol. 179(1):346-56, 2007.
Yun YH, Dong Z, Shanov VN, Heineman WR, Halsall HB, Bhattacharya A, Conforti L, Narayan RK, Ball WS, Schulz MJ. :Nanotube electrodes and biosensors. Nanotoday 2: 30-37, 2007.
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