William W. Morgan, Ph.D., Professor
Indiana University
1970

(210) 567-3816
MORGAN@UTHSCSA.EDU

Dr. Morgan is the course director for Experimental Design and Data Analysis, lecturer and laboratory instructor for Medical Microanatomy, and lecturer for the new Fundamentals of Neuroscience course. He is the chair of the mock grant proposal committee for the Graduate Program in Cellular and Structural Biology and chairs the Departmental Promotions, Tenure and Appointments Committee. He is a frequent reviewer of manuscripts for Biology of Reproduction and Brain Research.

My research interests are focused on two closely related areas. The first is the elucidation of the molecular genetic mechanisms involved in regulating the tissue-specific expression of the tyrosine hydroxylase (TH) gene. Tyrosine hydroxylase is the rate-limiting enzyme in the biosynthesis of catecholamine neurotransmitters and is expressed only in those neurons which normally synthesize and release these compounds. We have developed a number of transgenic mouse lines that express chimeric constructs in which the transcription of an E. coli b-galactosidase (lac Z) or luciferase reporter gene is placed under the control of the 5' regulatory sequence of the mouse TH gene. These constructs direct the expression of lacZ (blue color) to TH immunopositive neurons (brown color) in the substantia nigra (see figure).  

My second research interest relates to the role of reactive oxygen species (ROS) and of inflammatory processes in the etiology of Parkinson's disease. Parkinson's disease (PD) is a severely debilitating motor disorder characterized by rigidity, tremor and a progressive loss of the ability to initiate voluntary movement. It is a disease that is associated with aging, appears usually in the fifth or sixth decade of life, and is ultimately the result of a selective and incremental loss of dopamine (DA)-releasing neurons in the substantia nigra (SN).

Although the underlying mechanisms responsible for the progressive loss of these neurons remain undefined, there is increasing evidence for an inflammatory response in the substantia nigra (SN) of the parkinsonian brain. Whether inflammation occurs early or late in the progression of PD, it is possible that this process may serve a protective role for the surviving nigral DA neurons or alternatively may contribute to the continued degeneration of these neurons. Therefore, the study of the effects of inflammatory processes on the viability of nigral DA neurons is an important and potentially highly clinically relevant topic of investigation. We are currently using primary cultures of mesencephalic neurons as well as a number of gene knockout models to investigate the potential influence of the expression of several proinflammatory cytokines on the PD-like degeneration of nigral DA neurons following 1-methyl-4-phenyl-2,3,4,6,-tetrahydropyridine (MTPT) administration.

PUBLICATIONS:
Kalkonde, Y.V., Morgan, W.W., Sigala, J.A., Maffi, S.K., Condello, C., Kuziel, W.A., Ahuja, S.S. and Ahuja, S.K. (2006) Chemokines in the MPTP model of Parkinson's disease: absence of CCL2 and its receptor CCR2 does not protect against striatal neurodegeneration. Brain Res. In press.

Morgan,W.W., Richardson,A.. and Nelson, J.F. (2003) Dietary restriction does not protect the nigrostriatal dopaminergic pathway of older animals from low dose MPTP-induced neurotoxicity. J. Gerontol. A Biol. Sci. Med. Sci. 58(5): B394-399.

Corbitt,J., Hagerty,T., Fernandez,E., Morgan,W.W. and Strong,R.A. (2002) Transcriptional and posttranscriptional regulation of tyrosine hydroxylase messenger RNA in PC12 cells during persistent stimulation by VIP and PACAP 38: Differential regulation by protein kinase A and protein kinase C-dependent pathways. Neuropeptides 36: 34-45.

Foster, D., Strong, R. and Morgan, W.W. (2001) A tetracycline-repressible transactivator approach suggests a shorter half-life for tyrosine hydroxylase mRNA. Brain Res. Brain Res. Protocols 7: 137-146.

Hagerty,T., Fernandez,E., Lynch,K., Wang,S-S., Morgan, W.W. and Strong, R.A. (2001) Interaction of a glucocorticoid responsive element with regulatory sequences in the promoter region of the mouse tyrosine hydroxylase gene. J. Neurochem. 78(6): 1379-1388.

Morgan,W.W. and Nelson, J.F. (2001) Chronic administration of pharmacological levels of melatonin does not ameliorate the MPTP-induced degeneration of the nigrostriatal pathway. Brain Res. 921(1-2): 115-121.