Layton Smith, Ph.D.

Layton Smith, Ph.D. headshot

Layton Smith, Ph.D.

Executive Director, Preclinical Research

Layton Smith's Research Focus

Cardiovascular Diseases, Atherosclerosis, Hypertension, Metabolic Syndrome

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 SBP, 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.

Cardiovascular Metabolism Accessory


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

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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

A Pharmacochaperone-Based High-Throughput Screening Assay for the Discovery of Chemical Probes of Orphan Receptors.

Morfa CJ, Bassoni D, Szabo A, McAnally D, Sharir H, Hood BL, Vasile S, Wehrman T, Lamerdin J, Smith LH

Assay Drug Dev Technol 2018 Oct ;16(7):384-396

Repurposing antimalarial aminoquinolines and related compounds for treatment of retinal neovascularization.

McAnally D, Siddiquee K, Gomaa A, Szabo A, Vasile S, Maloney PR, Divlianska DB, Peddibhotla S, Morfa CJ, Hershberger P, Falter R, Williamson R, Terry DB, Farjo R, Pinkerton AB, Qi X, Quigley J, Boulton ME, Grant MB, Smith LH

PLoS One 2018 ;13(9):e0202436

Downregulation of the Apelinergic Axis Accelerates Aging, whereas Its Systemic Restoration Improves the Mammalian Healthspan.

Rai R, Ghosh AK, Eren M, Mackie AR, Levine DC, Kim SY, Cedernaes J, Ramirez V, Procissi D, Smith LH, Woodruff TK, Bass J, Vaughan DE

Cell Rep 2017 Nov 7 ;21(6):1471-1480

Capzimin is a potent and specific inhibitor of proteasome isopeptidase Rpn11.

Li J, Yakushi T, Parlati F, Mackinnon AL, Perez C, Ma Y, Carter KP, Colayco S, Magnuson G, Brown B, Nguyen K, Vasile S, Suyama E, Smith LH, Sergienko E, Pinkerton AB, Chung TDY, Palmer AE, Pass I, Hess S, Cohen SM, Deshaies RJ

Nat Chem Biol 2017 May ;13(5):486-493

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