Immunology & Infectious Diseases

Laura ConfortiLaura Conforti, PhD

Internal Medicine- Nephrol & Hyprtnsion

Associate Professor

Research Summary

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:

  • Cancer: 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. We are now investigating the mechanisms responsible for ion channel downregulation in hypoxia.
  • Autoimmune diseases: 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 therapeutic intervention. We are now studying the mechanisms responsible for the abnormal ion channel function in these patients. We also are investigating novel immunosuppressive therapies targeting ion channels based on nanoparticle delivery of drugs and siRNAs.
  • T cell activation: 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. We are working in collaboration with the Department of Engineering to design artificial antigen presenting cell arrays that will allow us to look into the immunological synapse and determine what happens at this site.

The techniques used in the laboratory include, but are not limited to, electrophysiology, molecular biology, fluorescence and confocal microscopy. Furthermore, novel nanotechnology methods are currently applied.

Recent Publications

Nyakeriga AM, Fichtenbaum CJ, Goebel J, Nicolaou SA, Conforti L, Chougnet CA. Engagement of the CD4 receptor affects the redistribution of Lck to theimmunological synapse in primary T cells: implications for T-cell activationduring human immunodeficiency virus type 1 infection. J Virol. 2009Feb;83(3):1193-200. Epub 2008 Nov 19. PubMed PMID: 19019957; PubMed CentralPMCID: PMC2620884.

Nicolaou SA, Szigligeti P, Neumeier L, Lee SM, Duncan HJ, Kant SK, Mongey AB, Filipovich AH, Conforti L. Altered dynamics of Kv1.3 channel compartmentalizationin the immunological synapse in systemic lupus erythematosus. J Immunol. 2007 Jul1;179(1):346-56. PubMed PMID: 17579055; PubMed Central PMCID: PMC2453311.

Nicolaou SA, Neumeier L, Peng Y, Devor DC, Conforti L. The Ca(2+)-activatedK(+) channel KCa3.1 compartmentalizes in the immunological synapse of human Tlymphocytes. Am J Physiol Cell Physiol. 2007 Apr;292(4):C1431-9. Epub 2006 Dec 6.PubMed PMID: 17151145; PubMed Central PMCID: PMC2553516. 

Li HC, Li EY, Neumeier L, Conforti L, Soleimani M. Identification of a novelsignal in the cytoplasmic tail of the Na+:HCO3- cotransporter NBC1 that mediates basolateral targeting. Am J Physiol Renal Physiol. 2007 Apr;292(4):F1245-55. Epub2006 Dec 19. PubMed PMID: 17182531.

Yun Y.H., Dong Z., Shanov V.N., Heineman W.R., Halsall H.B., Bhattacharya A., Conforti L., Narayan R.K., Ball W.S. and Schulz M.J. Nanotube electrodes and biosensors. Nanotoday 2: 30-37, 2007.

Szigligeti P, Neumeier L, Duke E, Chougnet C, Takimoto K, Lee SM, FilipovichAH, Conforti L. Signalling during hypoxia in human T lymphocytes--critical roleof the src protein tyrosine kinase p56Lck in the O2 sensitivity of Kv1.3channels. J Physiol. 2006 Jun 1;573(Pt 2):357-70. Epub 2006 Apr 6. PubMed PMID:16600997; PubMed Central PMCID: PMC1779731.

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