Layton Smith's Research Focus
Dr. Layton Smith has extensive training in both experimental and clinical pharmacology, and during the last six years has worked on numerous collaborative research projects as part of the Prebys Center’s efforts to reimagine the early drug discovery process and find innovative new medicines based upon discoveries made in university research labs across the US.
The Smith lab focuses on identifying molecular mechanisms of increased risk for cardiovascular disease in the metabolic syndrome, by studying apelin, a vasoactive peptide that increases cardiac contractility and decreases vascular tone to reduce blood pressure. Paradoxically, this vasoprotective peptide is over-produced by fat in obese people, but fails to elicit the positive effects on the cardiovascular system. To address this paradoxical effect, Smith employs molecular biology, cellular and animal models, novel pharmacologic tools and is currently developing cell-based assays to identify small molecule probes of the apelin receptor using an HTS strategy.
Layton Smith's Bio
Dr. Layton Smith is the Director of Drug Discovery and Exploratory Pharmacology for the Conrad Prebys Center for Chemical Genomics (Prebys Center) at Sanford Burnham Prebys Medical Discovery Institute at Lake Nona (SBP). He is also the Principal Investigator for the Florida Translational Research Program at SBP, Florida’s state-funded program for drug discovery.
Prior to joining Sanford Burnham Prebys, Layton was the Associate Director of Pharmacology at The Scripps Research Institute where he led the in vitro ADME/T and in vivo DMPK teams in support of several discovery projects spanning oncology, diabetes, and vascular diseases. After moving to SBP, he established a Pharmacology core facility to complement the small molecule discovery platforms already in existence. In 2009, Layton was promoted to Director of Drug Discovery. Since then, he has been involved in center leadership, strategic planning, and in the coordination of effort between the project teams of the Center and its collaborators to execute projects on schedule and on budget.
Layton received his doctorate degree (Pharmacology, 2002) from Vanderbilt University, Nashville, Tennessee, where he also received his postdoctoral training in Clinical Pharmacology and Cardiovascular Medicine.
Publications
Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription.
Chen Y, Zhou K, Wang R, Liu Y, Kwak YD, Ma T, Thompson RC, Zhao Y, Smith L, Gasparini L, Luo Z, Xu H, Liao FF
Proc Natl Acad Sci U S A 2009 Mar 10 ;106(10):3907-12
Pivotal role of PAI-1 in a murine model of hepatic vein thrombosis.
Smith LH, Dixon JD, Stringham JR, Eren M, Elokdah H, Crandall DL, Washington K, Vaughan DE
Blood 2006 Jan 1 ;107(1):132-4
Plasminogen activator inhibitor-1: a common denominator in obesity, diabetes and cardiovascular disease.
De Taeye B, Smith LH, Vaughan DE
Curr Opin Pharmacol 2005 Apr ;5(2):149-54
Novel and Structurally Diversified Bacterial DNA Gyrase Inhibitors Discovered through a Fluorescence-Based High-Throughput Screening Assay.
Alfonso EE, Deng Z, Boaretto D, Hood BL, Vasile S, Smith LH, Chambers JW, Chapagain P, Leng F
ACS Pharmacol Transl Sci 2022 Oct 14 ;5(10):932-944
Development and use of a high-throughput screen to identify novel modulators of the corticotropin releasing factor binding protein.
Haass-Koffler CL, Francis TC, Gandhi P, Patel R, Naemuddin M, Nielsen CK, Bartlett SE, Bonci A, Vasile S, Hood BL, Suyama E, Hedrick MP, Smith LH, Limpert AS, Roberto M, Cosford NDP, Sheffler DJ
SLAS Discov 2022 Oct 7 ;
Concentration and proteolysis of CX3CL1 may regulate the microglial response to CX3CL1.
Finneran D, Li Q, Subbarayan MS, Joly-Amado A, Kamath S, Dengler DG, Gordon MN, Jackson MR, Morgan D, Bickford PC, Smith LH, Nash KR
Glia 2022 Sep 15 ;
Optimization of a urea-containing series of nicotinamide phosphoribosyltransferase (NAMPT) activators.
Pinkerton AB, Sessions EH, Hershberger P, Maloney PR, Peddibhotla S, Hopf M, Sergienko E, Ma CT, Smith LH, Jackson MR, Tanaka J, Tsuji T, Akiu M, Cohen SE, Nakamura T, Gardell SJ
Bioorg Med Chem Lett 2021 Jun 1 ;41:128007
Discovery of small molecule antagonists of chemokine receptor CXCR6 that arrest tumor growth in SK-HEP-1 mouse xenografts as a model of hepatocellular carcinoma.
Peddibhotla S, Hershberger PM, Jason Kirby R, Sugarman E, Maloney PR, Hampton Sessions E, Divlianska D, Morfa CJ, Terry D, Pinkerton AB, Smith LH, Malany S
Bioorg Med Chem Lett 2020 Feb 15 ;30(4):126899
Discovery of β-Arrestin Biased, Orally Bioavailable, and CNS Penetrant Neurotensin Receptor 1 (NTR1) Allosteric Modulators.
Pinkerton AB, Peddibhotla S, Yamamoto F, Slosky LM, Bai Y, Maloney P, Hershberger P, Hedrick MP, Falter B, Ardecky RJ, Smith LH, Chung TDY, Jackson MR, Caron MG, Barak LS
J Med Chem 2019 Sep 12 ;62(17):8357-8363
