John M. Lee, MD, PhD Professor of Pathology, Pharmacology and Neuroscience (888) LUHS-888

Dr. Lee's research interests include the following ongoing projects

Animal Models of Alzheimer's Disease (AD): Currently, Dr. Lee's lab is investigating the neurotoxic effects of in vivo injections of ß-amyloid, the major component of senile plaques in Alzheimer's disease. Using this paradigm in the rat CNS, they have been able to induce abnormal forms of tau, a microtubule-associated protein which comprises neurofibrillary tangles.

Clinicopathological Correlations of Neurodegenerative Diseases: His lab is also investigating pathological variants of Alzheimer's disease. One variant is diffuse Lewy body disease (DLBD). This variant has ß-amyloid deposition, as in AD. However, rather than neurofibrillary tangles, intraneuronal Lewy bodies are found. The distribution and composition of these Lewy bodies is different than neurofibrillary tangles, suggesting that DLBD may be a distinct pathological entity.

Receptor/G-protein Coupling in Normal and AD Brains: Dr. Lee's lab has demonstrated that the ability of neurotransmitter agonists to bind to their respective synaptic receptors is altered in AD. Specifically, the ability for acetylcholine and serotonin to bind to their receptors is lowered. These two neurotransmitter systems are profoundly affected in AD. Based on additional experiments, it appears that the ability of these receptors to couple to their second messengers through G-proteins is markedly altered. Therefore, no matter how much neurotransmitter is present in the synapse, no transmembrane signal can be induced.

Neuroanatomy and Pharmacology of Mammalian Neurokinin Systems: Substance P is a Neurokinin 1 receptor agonist. It is the most well-described member of the neurokinin family of peptides. In addition, Substance P, neurokinin A (NKA), and neurokinin B (NKB) have been isolated and described in rodents. Presently, Dr. Lee's lab is determining the neuroanatomy of the NKB system in the primate and human CNS.

In addition, they have established the Loyola University Brain Bank. The Brain Bank is a university and regional resource for neuroscientists. At the present time, neurodegenerative diseases and age-matched controls are being collected. This material can be used for studying AD as well as the effects of aging in the human CNS.

Publications

View a partial list of Dr. Lee's publications through the National Library of Medicine's PubMed online database.