Overview

Dept. of Neuroscience, Albert Einstein College of Medicine, Postdoctoral Fellow 1979-1082

Dept. of Biology, Stanford University, Postdoctoral Fellow 1982-1984

Dept. of Anatomy and Cell Biology, Harvard Medical School, Research Associate 1984-1985

Physical Science Laboratory, DCRT, National Institutes of Health, Staff Fellow 1985

Dept. of Biophysics, Johns Hopkins University, Assistant Professor 1985-1991

Dept. of Biophysics, Johns Hopkins University, Associate Professor 1991-1998

Laboratory of Cellular and Molecular Biophysics, NICHD, National Institutes of Health, Visiting Scientist 1996-1997

Dept. of Pharmacology and Physiology, New Jersey Medical School, Associate Professor 1998-2005

Dept. of Pharmacology and Physiology, New Jersey Medical School, Professor 2005-2015

Dept. of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Professor 2015 - present

Education

PHD, 1979, Stanford University
B.A., 1972, University of California

Relevant Publications

Jiang, W., Lin, Y.C., Botello-Smith, W., Contreras, J., Harris, A.L., Maragliano, L. and Luo, Y.L. (2021) Free energy and kinetics of cAMP permeation through connexin26 via applied voltage and milestoning. Biophys. J. 120:2969-2983

Jagielnicki, M., Kucharska, I., Bennett, B.C., Harris, A.L. and Yeager, M. (2024) Connexin gap junction channels and hemichannels: insights from high-resolution structures. Biology 13:298

Gaete, P.S.G., Kumar, D., Fernandez, C.I., Valdez-Capuccino, J.M., Bhatt, A., Jiang, W., Lin, Y.C., Liu, Y., Harris, A.L., Luo, YL, Contreras, J.E. (2024) Large-pore connexin hemichannels function like molecule transporters independent of ion conduction. Proc. Natl. Acad. Sci. USA 121:e2403903121.

Kumar, D., Harris, A.L., Luo, Y.L. (2024) Molecular permeation through large pore channels: Computational approaches and insights. J. Physiol. (Lond.) online ahead of print Oct. 7.

Harris, A.L. (2018) Electrical coupling and its channels. J. Gen. Physiol. 50:1606-1639

Lopez, W., Ramachandran, J., Alsamarah, A., Luo, Y., Harris, A.L. and Contreras, J.E. (2016) Mechanism of gating by calcium in connexin hemichannels. Proc. Natl. Acad. Sci. USA 113:E7986-E7995

Luo, Y., Rossi, A.R., Harris, A.L. (2016) Computational studies of molecular permeation through connexin26 channels. Biophys. J. 110:584-599

Harris, A.L. and Contreras, J.E. (2014) Motifs in the permeation pathway of connexin channels mediate voltage and Ca2+ sensing. Frontiers Physiol. 5:113

Lopez, W, Gonzalez, J., Liu, J., Harris, A.L. and Contreras, J.E. (2013) Insights on the mechanisms of Ca2+ regulation of connexin 26 hemichannels revealed by human pathogenic mutations (D50N/Y). J. Gen. Physiol. 42:23-35

Kwon, T., Roux, B., Jo, S., Klauda, J.B., Harris, A.L. and Bargiello, T.A. (2012) Molecular dynamics simulations of the Cx26 hemichannel: Insights into voltage-dependent loop-gating. Biophys. J. 102:1341-1351

Course List

CBNP5036Q

Mol Phys of Cell Comm

Our research interest is the structure-function of connexin channels. Connexin channels form wide pores that are permeable to ions and small molecules. They compose gap junctions, providing a direct intercellular pathway by which signaling molecules to pass from one cell to another. Gap junctions are found between most cells in the body throughout development and adulthood. Connexins also form channels in plasma membrane that mediate ionic and molecular flux between the inside and outside of cells, primarily in pathological circumstances. The molecular signaling mediated by connexin channels is crucial for normal development, physiology and response to disease and trauma. Mutations in connexin proteins cause human pathologies.

Our research investigates the structure-function of connexin channels - what they do, how they work and how they are modulated. We have investigated their voltage sensitivity, molecular selectivity, post-translational modifications, isoform-specific lipid associations, and gating by pH, aminosulfonates and Ca2+. We employ biophysical, biochemical, genetic, cellular and computational approaches. Most recently we have focused on understanding the mechanisms of molecular permeation through connexin channels to reveal the determinants of permeation and selectivity.