Ph.D. in Genetics awarded by Harvard University, Department of Genetics, Division of Medical Sciences.
Key Words: Free radicals, superoxide, NO, CNS, motor neuron, ALS, spinal cord, spinal regeneration, neurister, neuristor
Previous Position :
Instructor of Medicine at Harvard Medical School.
1. Induced Adaptive Resistance to NO in the CNS.
Neurons release and utilize low levels of the free radical, nitric oxide (NO), for cellular signaling and neurotransmission. At high levels (can be >1mM), typically released during CNS injury and disease, NO is toxic. We have found that when motor neurons, both the NSC34 motor neuron cell line and primary motor neurons, are exposed to low doses of NO (~25nM) they become resistant (as assayed by significantly decreased DNA damage and apoptosis) to normally toxic levels of NO (~300nM-1mM). We have dubbed this phenomenon, induced adaptive resistance (IAR). IAR is dependent on the heme metabolizing enzyme, heme oxygenase 1 (HO1), as demonstrated by the loss of resistance upon the incubation of motor neurons with an HO1 inhibitor, and by the absence of resistance in motor neurons isolated from HO1 null mice. IAR extends to peroxide which is a product of the metabolism of superoxide, a free radical also released during CNS disease and injury. One proposed cause of NO-mediated cell death is extensive protein nitration by peroxynitrite, a molecule formed by the combination of superoxide with NO. IAR cells have significantly decreased levels of protein nitration in response to toxic levels of NO as compared to non adapted cells. In addition, motor neurons isolated from HO1 null mice have elevated levels of nitrated proteins in response to toxic levels of NO as compared to cells isolated from wildtype animals. Taken together this data indicates that, in an HO1-dependent manner, IAR protects cell from free radical damage. Elucidation of the mechanisms IAR will allow us to mitigate free radical mediated damage seen in many CNS diseases and injury. The space flight environment (high radiation / low gravity) stresses cells and, in the case of high radiation, also leads to the production of free radicals, thereby underscoring the importance of understanding IAR.
2. Utilization of motor neurons for the development of the neurister/neuristor -neural circuits grown on novel biological computer chips.
This will be done with the ultimate goal of producing self-sustaining, high plasticity, analogue circuits. The neurister has applications for computer hardware as well as for neural bridges across spinal transections. Initial (quite preliminary) experiments have been performed. This work will be pursued upon acquisition of funding.
Most recent, relevant publications:
Renae Gooch, James Anderson, Bruce Demple, Amy Bishop, (2005) Mitigation of nitrotyrosine formation in motor neurons adapted to nitrooxidative stress. Manuscript in preparation.
Amy Bishop & James Anderson. NO signaling in the CNS: from the physiological to the pathological. (2005). TOXICOLOGY (Special Issue) Nitric Oxide, Cell Signaling and Death Edited by João Laranjinha.
Amy Bishop, Shaw Fung-Yet, Mark J. Perrella, Arthur M. Lee, Neil R. Cashman and Bruce Demple (2004) Decreasedresistance to nitric oxide in motor neurons of HO-1 null mice. BBRC 325:3-9
Amy Bishop, NO signaling in the CNS (2003) Invited chapter of the special issue NO, Cell Signaling and Death, edited by Dr. Joao Antonio Nave Laranjinha.
Amy Bishop, Shaw Fung-Yet, Mark J. Perrella, Arthur M. Lee, Neil R. Cashman and Bruce Demple Decreased resistance to nitric oxide in motor neurons of HO-1 null mice. (2003) (in revision).
Amy Bishop, Neil R. Cashman. (2003) Induced adaptive resistance to oxidative stress in the CNS: Discussion of possible mechanisms and their therapeutic potential. Current Drug Metabolism 4(2) 171-184.[PDF]
Amy Bishop, John C. Marquis, Neil R. Cashman, and Bruce Demple (1999) Adaptive resistance to nitric oxide in motor neurons. Free Radical Biology & Medicine 26(7/8) 978-986.[PDF]
Courses Taught at UAH
BYS 313: Anatomy & Physiology 1
BYS 314: Anatomy & Physiology 2
BYS 400/600: Introduction to Neuroscience
Special Topics 691: Mechanisms of resistance to oxidative stress in the CNS
Special Topics 692: Research
Kimberly Green, Bridge to Doctorate Student
Renea Gooch, Masters Student
James Anderson, Research Consultant, Cherokee Labsystems
Robert Richmond, Ph.D., Marshall Space Flight Center, NASA
National Space Science & Technology Center, Huntsville, AL.