Wellington Pham
Professor of Radiology and Radiological Sciences
Professor of Biomedical Engineering
Intellectual Neighborhoods
Research Focus
The main work in this lab focuses on integrating medicinal chemistry with molecular imaging to validate biomarkers along the amyloid-cascade mechanism for imaging Alzheimer’s disease (AD). We develop novel PET probes, including [11C]promethazine, [11C]ergothioneine, and [18F]PB0822, for imaging amyloid plaques, oxidative stress, and pyroglutamate-3 amyloid, respectively. Aside from synthetic chemistry for developing the precursors and labeling methods, we also design biological assays to assess the specificity and efficacy of these probes. But the most exciting part of this multidisciplinary laboratory is translating our work into testing on preclinical animal models of AD. Currently, working in collaboration with colleagues from the Department of Pharmacology, we also develop a specific nanobody-based probe to detect AD several years before amyloid plaque formation.
Publications:
1. McClure RA, Chumbley CW, Reyzer ML, Wilson K, Caprioli RM, Gore JC, Pham W*, Identification of promethazine as an amyloid-binding molecule using a fluorescence high- throughput assay and MALDI imaging mass spectrometry. NeuroImage Clinical. 2013, 2, 620-629.
2. Barton S, Janve VA, McClure R, Anderson A, Matsubara JA, Gore JC and Pham W*., Lipopolysaccharide induced opening of the Blood Brain Barrier on Aging 5XFAD Mouse Model J Alzheimers Dis 2019, 67, 503-513
3. Barton SM, To E, Rogers B, Whitemore C, Matsubara JA, Pham W*. Inhalable thioflavin S for the detection of Abeta deposits in the retina. Molecules 2021, 26, 835.
4. Behof W, Whitmore C, Haynes J, Rosenberg A, Tantawy M, Harrison F, Beelman R, Pham W*. A novel antioxidant Ergothioneine PET radioligand for in vivo imaging, Scientific Reports 2021, 11 (1), 18450.
5. Behof WJ, Whitmore CA, Behof WJ, Haynes JR, Rosenberg AJ, Tantawy MN, Peterson TE, Harrison FE, Beelman RB, Wijeshinge P, Matsubara JA, Pham W*. Improved synthesis of an ergothioneine PET radioligand for imaging oxidative stress in Alzheimer’s disease, 2022 FEBS Letters. 2022, 596, 1279-1289.
6. Whitmore CA, Haynes JR, Behof WJ, Rosenberg AJ, Tantawy MN, Hachey BC, Wadzinski BE, Spiller BW, Peterson TE, Paffenroth KC, Harrison FE, Beelman RB, Wijesinghe P, Matsubara JA, Pham W*. Longitudinal consumption of ergothioneine reduces oxidative stress, amyloid plaques and restores glucose metabolism in the 5XFAD mouse model of Alzheimer’s disease. Pharmaceuticals 2022, 15, 742.
Biography
Professor Pham received his B.S. in Chemistry with honors from the University of Toledo and Ph.D. in Medicinal Chemistry in the same university. Following two postdoctoral fellowships at UCLA Medical School and Harvard Medical School in PET chemistry and molecular imaging, respectively; in 2005, he was an Instructor of Radiology at Harvard Medical School. He is currently an Assistant Professor of Radiology at Vanderbilt Medical School. He is a member of the editorial advisory boards for the Journal of Nanomedicine and Journal of Alzheimer's Disease.