I study the genetic and molecular basis of neurological and neuromuscular diseases of infancy and childhood. My research focuses on the molecules that make the nervous system and muscles excitable and on the molecules that supply energy to their cells.
As a universal principle, a disease starts with an alteration in the normal function of a cell, and abnormal function is always the consequence of a molecular abnormality. I devote equal efforts to understanding how molecules are designed to function under normal conditions, how genetic mutations alter their properties, and how these abnormal properties cause the diseases that we diagnose in the clinic. We have identified molecular areas in ion channels of neurons (Kv2.1) and muscle (the acetylcholine receptor) that are essential for the generation and propagation of electrical signals across these cells, and measured the electric fields in these small molecular regions using biophysical techniques. Related work focuses on mutant glucose transporters (Glut1) from patients with impaired glucose entry into the brain from the bloodstream. We have also discovered a new gene that is utilized by both primitive bacteria and human muscles alike for the movement of potassium inside and outside of them. We have also investigated new molecular therapies based on the control of gene expression and function.
Our laboratory attracts scientists and collaborators with diverse backgrounds that range from mathematics to genetics, electrophysiology, brain functional imaging or neuroscience, but with the common ability and shared vision to work on problems relevant to the human nervous and muscular systems and, more importantly, to the individuals afflicted by their diseases.
RESEARCH INTERESTS
Neurogenetic disorders
Neural excitability: synaptic transmission
Brain metabolism
Functional brain imaging
RECENT PUBLICATIONS
Pascual JM, Wang D, Hinton V, Engelstad K, Saxena CM, Van Heertum RL, De Vivo DC., "Brain Glucose Supply and the Syndrome of Infantile Neuroglycopenia" Arch. Neurol, 2007
Wang D, Pascual JM, Yang H, Engelstad K, Mao X, Cheng J, Yoo J, Noebels JL, De Vivo DC., "A mouse model for Glut-1 haploinsufficiency" Hum. Mol. Genet., 15:1169-79, 2006
J. M. Pascual, C.C. Shieh, G. E. Kirsch, A.M. Brown, "K+ pore structure revealed by reporter cysteines at inner and outer surfaces" Neuron, 14:1055-1063, 1995
J. M. Pascual, A. Karlin, "State-dependent accessibility and electrostatic potential in the channel of the acetylcholine receptor" J. Gen. Physiol., 111:717-739, 1998
J. M. Pascual, A. Karlin, "Delimiting the binding site for quaternary ammonium lidocaine derivatives in the acetylcholine receptor channel" J. Gen. Physiol., 112:611-621, 1998
J. M. Pascual, D. Wang, R.L. van Heertum, K. Engelstad, D.C. De Vivo, "Imaging the footprint of Glut1 deficiency on the brain" Ann. Neurol., 52:458-464, 2002
Pascual JM, Wang D, Lecumberri B, Yang H, Mao X, Yang R, De Vivo DC., "GLUT1 deficiency and other glucose transporter diseases" Eur. J. Endocrinol., 150:627-33, 2004
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