Welcome to the Harris Lab Site

Brent T. Harris, MD, PhD Dartmouth Medical School

Lab Folks Protocols (under construction) CV and Publications

ALS Center of DHMC

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Pathology Links

Pathology Teaching

Neuropathology Links Interesting Neuropathology Cases from the DHMC files

Collaborations

 


What's going on in the Harris Lab - Overview

You can find the Harris Lab at the Dartmouth-Hitchcock Medical Center in the Borwell Research Building - 510W (see map).

Mailing Address: Dr. Brent Harris, Dept of Pathology, One Medical Center Drive, DHMC, Lebanon, NH 03756

email: bharris@dartmouth.edu


CURRENT PROJECTS

Why do upper and lower motor neurons degenerate in ALS? Our ability to move our arms and legs depends on the integrity of our spinal motor neurons, which relay electrical signals from our brain to our muscles. When these motor neurons die, as can occur in injury or in a variety of degenerative diseases that affect infants and children (spinal muscular atrophies) or adults (ALS) irreversible paralysis or even death may ensue. Cortical upper motor neurons extend their axons great distances down to the spinal cord. For unknown reasons in ALS, this select group of neurons in the cerebrum atrophy and die similar to the lower motor neurons in the spinal cord. A number of transgenic animal models for ALS exist based on the superoxide dismutase (SOD1) gene mutations found in a portion of familial ALS patients. These animals display similar clinical symptoms and histopathology to that found in human motor neuron disease. Thus, it is now possible and crucial to understand the signaling mechanisms that normally promote upper and lower motor neuron survival and how these processes go awry in motor neuron diseases.

Our lab is focusing on understanding the basic cellular and molecular pathogenesis of ALS by studying defined neuronal and glial cells in culture that may be important in the degeneration and survival of motor neurons. In addition, we use rodent animal models of the disease to see how these cells and molecules interact in a complex organism that gets an ALS-like disease. Finally, we are studying epidemiology and human genetic polymorphisms of ALS in New England and working with neurologists here at the ALS Center of DHMC to test new therapeutics in clinical trials with our patients.


Axonal transport and mitochondrial dysfunction have been implicated in the pathogenesis of ALS. In collaboration with Elijah Stommel, MD, PhD from the division of Neurology we have undertaken a project to examine axonal transport of mitochondria and vessicles in purified cultures of spinal motor neurons.

Panel 1.Representative DIC computer enhanced image of MN with vesicles (A) and mitochondria (B) moving in antero- and retrograde directions. Panel 2: Fluorescently labelled mitochondria moving in MN processes. Click on the images to view movies of axonal transport in progress.


Tissue Arrays are a promising new technology that allows controlled sampling of dozens to hundreds of tissue samples on a single slide. Our laboratory is interested in using this technique to study brain, spinal cord, and nerve tumors.


COLLABORATIONS:

Our lab is also committed to providing expertise in neuropathology and neuroscience techniques to the Dartmouth neuroscience community, and we have established collaborations with individuals from Pathology, Neurology, Neurosurgery, Biochemisty, Pharmacology, NCCC, and Physiology.