Despite strong evidence for the association of melatonin with circadian rhythm and mental health, its function is poorly understood. We seek to develop inhibitors of the key enzyme involved in making melatonin, serotonin N-acetyl-transferase (SNAT, AANAT), to better understand its function and for use as drug candidates for treating disorders in which it is abnormally high, such as seasonal affective disorder (SAD). Our team includes UNK professors Allen Thomas (PI), Michael Moxley, Evan Hill and Surabhi Chandra in addition to external collaborators Profs. Philip Cole (Harvard), Ryan Wong (UNO) and Mark Wilson (UNL). We will apply computational and experimental approaches including medicinal chemistry and zebrafish models of sleep to discover and optimize inhibitors to overcome weaknesses of earlier attempts at blocking melatonin synthesis. This project is funded by a National Institutes of Health (NIH) Academic Research Enhancement Award (AREA; R15 HL165700) through the National Heart, Lung and Blood Institute (NHLBI).
Thomas, A. A.; Chien, H.-C.; Zur, A. A.; Giacomini, K. M.; Colas, C.; Schlessinger, A.; Lin, L.; Finke, K.; Augustyn, E.; Springer, S.; Stoner, L.; Flint, A.; Heeren, N.; Hansen, L.; Anthony, A.; Hernandez, C.; Venteicher, B.; Campbell, J.; Hall, C.
Springer, S.; Stoner, L.; Finke, K.; Anthony, A.; Flint, A.; Bauer, J.; Hernandez, C.; Chien, H.-C.; Giacomini, K. M.; Colas, C.; Schlessinger, A.; Thomas, A. A.
Venteicher, B.; Hall, C.; Campbell, J.; Hernandez, C.; Flint, A.; Chien, H.-C.; Giacomini, K. M.; Colas, C.; Schlessinger, A.; Thomas, A. A.
Hall, C.; Venteicher, B.; Chien, H.-C.; Giacomini, K. M.; Colas, C.; Schlessinger, A.; Thomas, A. A.
Brooklynn, Colton, Dr. Thomas, Seth
Brooklynn, Seth, Colton, Dr. Thomas
In 2017, Dr. Thomas received a National Institutes of Health (NIH) Academic Research Enhancement Award (AREA) through the National Institute of Neurological Disorders and Stroke (NINDS) for a project entitled “Identification of new LAT-1 transporter substrates for drug delivery” (R15 NS099981). His research group seeks to exploit one of the body’s natural mechanisms for transporting amino acids, the LAT-1 protein, for targeted drug delivery across the blood-brain barrier (BBB) and cancer cells that express this transporter. Guided by computational models developed in collaboration with Prof. Avner Schlessinger at Icahn School of Medicine at Mt. Sinai, students in the Thomas lab apply organic chemistry techniques to synthesize amino acid mimetics and drug-amino acid conjugates, which are then tested in cells engineered to express LAT-1 by his collaborator, Dr. Kathleen Giacomini at University California San Francisco. This research project has broad applications for treating many different diseases both in the brain and other tissues where LAT-1 is heavily expressed, including cancer.