Daniel C Lee, PhD
- Associate Professor, Department of Neuroscience
Biography and Education
I attended Lincoln University from 1995-1999 and graduated with a BS degree in chemistry. My grandfather also named Daniel Lee, MD and graduate of Lincoln University was diagnosed with Parkinson’s disease. I pursued a degree at Florida A&M University College of Pharmacy & Pharmaceutical Science in 1999 to study Parkinson’s disease with Donald E. Palm, PhD. and graduated in 2005 with a PhD in Pharmaceutical Sciences/ Neuropharmacology. During this time my grandfather was later diagnosed with Alzheimer’s disease or importantly some form of dementia. I pursue my postdoctoral training in an Alzheimer’s disease research lab at University of South Florida College of Medicine with Dave Morgan and Marcia Gordon in 2005. Together, we studied the role of neuroinflammation, microglial activation and the impact of aging in animal models of amyloid and tau deposition. This area of research launched the investigation of arginine metabolism and polyamine biology in Alzheimer's disease and tauopathies. I joined the newly formed USF Teneja College of Pharmacy as a founding member and assistant professor in 2010 and was later promoted to associated professor/ tenure in 2017. In 2018, I was appointed Director of Neurogenerative Sciences in USF College of Pharmacy and the William N. Sanders Endowed Chair in Geriatric Pharmacotherapy. In August of 2019, I was recruited and joined the University of Kentucky College of Medicine Sanders-Brown Center on Aging in the Department of Neuroscience.
1999 B.S. Chemistry Lincoln University, Lincoln University, PA 2005 Ph.D. Pharmaceutical Sciences Florida A&M University College of Pharmacy & Pharmaceutical Science, Tallahassee, FL 2005 Post-doctoral fellow/ Neuroscience; University of South Florida College of Medicine Tampa, FL 2010 Assistant Professor (Founding Faculty); Dept. Pharmaceutical Sciences College of Pharmacy, University of South Florida, Byrd Alzheimer’s Institute 2017 Associate Professor (Tenured), Dept. Pharmaceutical Sciences College of Pharmacy, University of South Florida, Byrd Alzheimer’s Institute 2018 Director of Neurodegenerative Sciences, College of Pharmacy, University of South Florida 2018 Appointed Endowment: William N. Sanders, College of Pharmacy, University of South Florida Chair in Geriatric Pharmacotherapy 2019 Adjunct Associate Professor, College of Medicine, University of South Florida, Dept. Molecular Medicine 2019 Associate Professor (Tenured), College of Medicine, University of Kentucky, Sanders-Brown Center on Aging, Dept. Neuroscience 2020 Co-Director of UK-ADRC REC University of Kentucky Sanders-Brown Center on Aging Research Education Component (REC)
There are 3 priority areas that my lab has established which apply to inflammation, arginine metabolism, amino acid sensing, and tauopathies (including Alzheimer’s disease). 1. The role of polyamine biology and the impact on tauopathies and other proteinopathies: The first area of focus involves role of polyamines (a product of arginine metabolism) during tauopathies. Our lab showed that bioactive polyamines directly block tau’s aggregation and promote microtubule assembly, but inactive acetylated polyamines fail to mimic this affect. We demonstrated the ability of physiological concentrations of “natural endogenous molecules” (polyamines) to inhibit the oligomerization/ aggregation of tau and could have wide applications because of tau’s ability to seed and promote the spread from one region of the brain to another. Polyamines interact differently with various tau strains. 2. The role of arginine-sensing mTORC1 activation and the impact on tauopathies and proteinopathies: The second area of focus is centered around arginine metabolism, which focuses on the receptor GPRC6a that may act as an extracellular sensor for arginine and mTORC1 signaling. GPRC6a binds L-α amino acids, particularly basic amino acids including L-arginine (high affinity), ornithine (high affinity), and L-lysine possibly through the Gq subunit. We hypothesize that decreased signaling of GPRC6a activates autophagy and tau clearance. We posit that GPRC6a receives tonic extracellular stimulation and senses the amino acids abundance, via L-arginine or derivative-like amino acids. Genetic targeting of GPRC6a essentially reduces the efficacy and functionality of the receptor, thereby nullifying endogenous ligands ineffective and signaling “amino acid deficiency” inducing autophagy. Recently, receptor variants have been identified in different ethnic populations that alter receptor trafficking and perhaps signaling. Imbalanced signaling could lead to loss or gain of function which could impact diseases that affect nutrient sensing and mTOR signaling in certain ethic populations. 3. The role of citrullination in tauopathies and proteinopathies. The third area of focus is on protein citrullination. Citrullination comprises of conversion of arginine to citrulline residues within proteins. This conversion permanently alters the target by producing loss of positive charges and changes in protein stability. Reports show hypercitrullination in rheumatoid arthritis, Alzheimer’s disease, and cancer. We identified tau and other disordered proteins become citrullinated. We hypothesize the aging and tau dysfunction promotes protein citrullination that further endorses the tau phenotype.