visualizations
Gardell, Stephen J, PhD
Overview
overview
- Dr. Gardell received his Ph.D. in Biochemistry from Cornell University Graduate School of Medical Sciences (NY, NY). His post-doctoral training in Molecule Biology was done at the University of California, San Francisco (UCSF), where he helped pioneer the use of site-directed mutagenesis to probe enzyme catalytic mechanisms. Dr. Gardell next spent 22 years in the drug discovery divisions of several major pharmaceutical companies (Merck, Bayer, Wyeth). The disease areas that were the target of his research pursuits included thrombosis, congestive heart failure, atherosclerosis, obesity, diabetes and Alzheimer’s disease. In 2009, Dr. Gardell joined the Sanford Burnham Prebys Medical Research Institute (SBP) in Orlando, Florida where he investigated an enzyme, nicotinamide phosphoribosyltransferase (NAMPT), which is the rate-determining step in NAD+ biosynthesis. He and his colleagues discovered small molecule activators of NAMPT that raise intracellular NAD+ levels, an effect with potential utility for a wide variety of diseases and healthy aging. While at SBP, Dr. Gardell also established a network of diverse technology cores and helped to direct the research operation. In May 2018, Dr. Gardell joined the Translational Research Institute in Orlando, Florida as a Senior Investigator where he continues his drug discovery research on NAMPT. In addition, Dr. Gardell established a Metabolomics Core at the TRI-MD which is a powerful technology platform to measure metabolites which serve to elucidate disease pathophysiology and unveil promising disease biomarkers..
Affiliation
Publications
Most Recent Publications
-
2024Genetic drivers of human plasma metabolites that determine mortality in heart failure patients with reduced ejection fraction. FRONTIERS IN CARDIOVASCULAR MEDICINE. 11.Full Text via DOI: 10.3389/fcvm.2024.1409340 PMID: 39045004
-
2024The TAS1R2 G-protein-coupled receptor is an ambient glucose sensor in skeletal muscle that regulates NAD homeostasis and mitochondrial capacity. NATURE COMMUNICATIONS. 15.Full Text via DOI: 10.1038/s41467-024-49100-8 PMID: 38851747
-
2023Comprehensive interrogation of human skeletal muscle reveals a dissociation between insulin resistance and mitochondrial capacity. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM. 325:E291-E302.Full Text via DOI: 10.1152/ajpendo.00143.2023 PMID: 37584609
-
2023Circulating Metabolomic Profile Predicts Change In Ejection Fraction In Heart Failure Patients. JOURNAL OF CARDIAC FAILURE. 569-569.
-
2023Source of nicotinamide governs its metabolic fate in cultured cells, mice, and humans. CELL REPORTS. 42.Full Text via DOI: 10.1016/j.celrep.2023.112218 PMID: 36897780
-
2023Exercise and ageing impact the kynurenine/tryptophan pathway and acylcarnitine metabolite pools in skeletal muscle of older adults. JOURNAL OF PHYSIOLOGY-LONDON.Full Text via DOI: 10.1113/JP284142 PMID: 36814134
-
2022NAD(+) and human muscle health. NATURE AGING. 195-196.Full Text via DOI: 10.1038/s43587-022-00192-1 PMID: 37118373
-
2021A Metabolomic Signature of Glucagon Action in Healthy Individuals With Overweight/Obesity. JOURNAL OF THE ENDOCRINE SOCIETY. 5.Full Text via DOI: 10.1210/jendso/bvab118 PMID: 34337278
-
2021Discovery of 1-[2-(1-methyl-1H-pyrazol-5-yl)-[1,2,4]triazolo[1,5-a] pyridin-6-yl]-3-(pyridin-4-ylmethyl)urea as a potent NAMPT (nicotinamide phosphoribosyltransferase) activator with attenuated CYP inhibition. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. 43.Full Text via DOI: 10.1016/j.bmcl.2021.128048 PMID: 33887438
-
2021Optimization of a urea-containing series of nicotinamide phosphoribosyltransferase (NAMPT) activators. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. 41.Full Text via DOI: 10.1016/j.bmcl.2021.128007 PMID: 33798699
-
2021Metabolic adaptation characterizes short-term resistance to weight loss induced by a low-calorie diet in overweight/obese individuals.. The American journal of clinical nutrition. 267-280.Full Text via DOI: 10.1093/ajcn/nqab027 PMID: 33826697
-
2019Boosting NAD(+) with a small molecule that activates NAMPT. NATURE COMMUNICATIONS. 10.Full Text via DOI: 10.1038/s41467-019-11078-z PMID: 31324777
-
2019Measurement of Pyridine Nucleotides in Biological Samples Using LC-MS/MS. METABOLOMICS: METHODS AND PROTOCOLS. 1996:61-73.Full Text via DOI: 10.1007/978-1-4939-9488-5_7 PMID: 31127548
-
2019Metabolomics Analyses of Muscle Atrophy Induced by Hind Limb Unloading. METABOLOMICS: METHODS AND PROTOCOLS. 1996:297-309.Full Text via DOI: 10.1007/978-1-4939-9488-5_22 PMID: 31127563
-
2018Impaired Mitochondrial Energetics Characterize Poor Early Recovery of Muscle Mass Following Hind Limb Unloading in Old Mice. JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES. 73:1313-1322.Full Text via DOI: 10.1093/gerona/gly051 PMID: 29562317
-
2018Elevated Nicotinamide Phosphoribosyl Transferase in Skeletal Muscle Augments Exercise Performance and Mitochondrial Respiratory Capacity Following Exercise Training. FRONTIERS IN PHYSIOLOGY. 9.Full Text via DOI: 10.3389/fphys.2018.00704 PMID: 29942262
-
2018Skeletal muscle overexpression of nicotinamide phosphoribosyl transferase in mice coupled with voluntary exercise augments exercise endurance. MOLECULAR METABOLISM. 7:1-11.Full Text via DOI: 10.1016/j.molmet.2017.10.012 PMID: 29146412
-
2017Targeted Metabolomic Profiling of Plasma and Survival in Heart Failure Patients. JACC-HEART FAILURE. 5:823-832.Full Text via DOI: 10.1016/j.jchf.2017.07.009 PMID: 29096792
-
2016Use of Ion Chromatography/Mass Spectrometry for Targeted Metabolite Profiling of Polar Organic Acids. ANALYTICAL CHEMISTRY. 88:11799-11803.Full Text via DOI: 10.1021/acs.analchem.6b03435 PMID: 27782384
-
2016Presence of arachidonoyl-carnitine is associated with adverse cardiometabolic responses in hypertensive patients treated with atenolol. METABOLOMICS. 12.Full Text via DOI: 10.1007/s11306-016-1098-2 PMID: 28217401
-
2016The Failing Heart Relies on Ketone Bodies as a Fuel. CIRCULATION. 133:698-705.Full Text via DOI: 10.1161/CIRCULATIONAHA.115.017355 PMID: 26819376
-
2013Rotenone induces reductive stress and triacylglycerol deposition in C2C12 cells. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY. 45:2749-2755.Full Text via DOI: 10.1016/j.biocel.2013.09.011 PMID: 24104397
-
2010Cardiovascular Drug Discovery in the Academic Setting: Building Infrastructure, Harnessing Strengths, and Seeking Synergies. JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH. 3:431-437.Full Text via DOI: 10.1007/s12265-010-9204-8 PMID: 20625868
-
2010Effect of the small molecule plasminogen activator inhibitor-1 (PAI-1) inhibitor, PAI-749, in clinical models of fibrinolysis. JOURNAL OF THROMBOSIS AND HAEMOSTASIS. 8:1333-1339.Full Text via DOI: 10.1111/j.1538-7836.2010.03872.x PMID: 20345708
-
2009LXR ligand lowers LDL cholesterol in primates, is lipid neutral in hamster, and reduces atherosclerosis in mouse. JOURNAL OF LIPID RESEARCH. 50:2358-2370.Full Text via DOI: 10.1194/jlr.M900037-JLR200 PMID: 19318684
-
2009Selective Kv1.5 Blockers: Development of (R)-1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone (KVI-020/WYE-160020) as a Potential Treatment for Atrial Arrhythmia. JOURNAL OF MEDICINAL CHEMISTRY. 52:6531-6534.Full Text via DOI: 10.1021/jm901042m PMID: 19888755
-
2009GAP-134 ([2S,4R]-1-[2-Aminoacetyl]-4-Benzamidopyrrolidine-2-Carboxylic Acid) Prevents Spontaneous Ventricular Arrhythmias and Reduces Infarct Size During Myocardial Ischemia/Reperfusion Injury in Open-Chest Dogs. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS. 14:207-214.Full Text via DOI: 10.1177/1074248409340779 PMID: 19721133
-
2009Activation of farnesoid X receptor prevents atherosclerotic lesion formation in LDLR-/- and apoE(-/-) mice. JOURNAL OF LIPID RESEARCH. 50:1090-1100.Full Text via DOI: 10.1194/jlr.M800619-JLR200 PMID: 19174369
-
2009The Gap Junction Modifier, GAP-134 [(2S,4R)-1-(2-Aminoacetyl)-4-benzamido-pyrrolidine-2-carboxylic Acid], Improves Conduction and Reduces Atrial Fibrillation/Flutter in the Canine Sterile Pericarditis Model. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. 329:1127-1133.Full Text via DOI: 10.1124/jpet.108.150102 PMID: 19252062
-
2009A synthetic farnesoid X receptor (FXR) agonist promotes cholesterol lowering in models of dyslipidemia. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY. 296:G543-G552.Full Text via DOI: 10.1152/ajpgi.90585.2008 PMID: 19136377
-
2008Indazole-Based Liver X Receptor (LXR) Modulators with Maintained Atherosclerotic Lesion Reduction Activity but Diminished Stimulation of Hepatic Triglyceride Synthesis. JOURNAL OF MEDICINAL CHEMISTRY. 51:7161-7168.Full Text via DOI: 10.1021/jm800799q PMID: 18973288
-
2008Effect of tiplaxtinin (PAI-039), an orally bioavailable PAI-1 antagonist, in a rat model of thrombosis. JOURNAL OF THROMBOSIS AND HAEMOSTASIS. 6:1558-1564.Full Text via DOI: 10.1111/j.1538-7836.2008.03063.x PMID: 18624980
-
2008Enhanced clearance of A beta in brain by sustaining the plasmin proteolysis cascade. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 105:8754-8759.Full Text via DOI: 10.1073/pnas.0710823105 PMID: 18559859
-
2007Small-molecule ghrelin receptor antagonists improve glucose tolerance, suppress appetite, and promote weight loss. ENDOCRINOLOGY. 148:5175-5185.Full Text via DOI: 10.1210/en.2007-0239 PMID: 17656463
-
2007Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity. JOURNAL OF MEDICINAL CHEMISTRY. 50:5202-5216.Full Text via DOI: 10.1021/jm070071+ PMID: 17887659
-
2007Neutralization of plasminogen activator inhibitor I (PAI-1) by the synthetic antagonist PAI-749 via a dual mechanism of action. MOLECULAR PHARMACOLOGY. 72:897-906.Full Text via DOI: 10.1124/mol.107.037010 PMID: 17622579
-
2006A presenilin-independent aspartyl protease prefers the gamma-42 site cleavage. JOURNAL OF NEUROCHEMISTRY. 96:118-125.Full Text via DOI: 10.1111/j.1471-4159.2005.03528.x PMID: 16300640
-
2005P-2 pyridine N-oxide thrombin inhibitors: a novel peptidomimetic scaffold. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. 15:2771-2775.Full Text via DOI: 10.1016/j.bmcl.2005.03.110 PMID: 15911253
-
2003Electrochemiluminescence assay for basic carboxypeptidases: inhibition of basic carboxypeptidases and activation of thrombin-activatable fibrinolysis inhibitor. ANALYTICAL BIOCHEMISTRY. 319:159-170.Full Text via DOI: 10.1016/S0003-2697(03)00252-5 PMID: 12842119
-
2003Presenilin-1 and presenilin-2 exhibit distinct yet overlapping gamma-secretase activities. JOURNAL OF BIOLOGICAL CHEMISTRY. 278:22475-22481.Full Text via DOI: 10.1074/jbc.M300974200 PMID: 12684521
-
2003Miniaturizable homogenous time-resolved fluorescence assay for carboxypeptidase B activity. ANALYTICAL BIOCHEMISTRY. 317:94-98.Full Text via DOI: 10.1016/S0003-2697(03)00048-4 PMID: 12729605
-
2003Pharmacokinetic optimization of 3-amino-6-chloropyrazinone acetamide thrombin inhibitors. Implementation of P3 pyridine N-oxides to deliver an orally bioavailable series containing P1N-benzylamides. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. 13:1353-1357.Full Text via DOI: 10.1016/S0960-894X(03)00099-4 PMID: 12657281
-
2003Metabolism-directed optimization of 3-aminopyrazinone acetamide thrombin inhibitors. Development of an orally bioavailable series containing P1 and P3 pyridines. JOURNAL OF MEDICINAL CHEMISTRY. 46:461-473.Full Text via DOI: 10.1021/jm020311f PMID: 12570369
-
2002gamma-Secretase: characterization and implication for Alzheimer disease therapy. NEUROBIOLOGY OF AGING. 23:1023-1030.PMID: 12470798
-
2001The Pro domain of beta-secretase does not confer strict zymogen-like properties but does assist proper folding of the protease domain. JOURNAL OF BIOLOGICAL CHEMISTRY. 276:10366-10373.PMID: 11266439
-
2001A beta pp secretases are co-expressed with A beta pp in the pancreatic islets. JOURNAL OF ALZHEIMERS DISEASE. 3:393-396.Full Text via DOI: 10.3233/JAD-2001-3405 PMID: 12214042
-
2000Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1. NATURE. 405:689-694.PMID: 10864326
-
2000Presenilin 1 is linked with gamma-secretase activity in the detergent solubilized state. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 97:6138-6143.PMID: 10801983
-
1999Characterization of plasmin-mediated activation of plasma procarboxypeptidase B - Modulation by glycosaminoglycans. JOURNAL OF BIOLOGICAL CHEMISTRY. 274:35046-35052.PMID: 10574983
-
1999Antithrombotic efficacy of thrombin inhibitor L-374,087: Intravenous activity in a primate model of venous thrombus extension and oral activity in a canine model of primary venous and coronary artery thrombosis. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. 289:503-510.PMID: 10087043
-
1998Efficacious, orally bioavailable thrombin inhibitors based on 3-aminopyridinone or 3-aminopyrazinone acetamide peptidomimetic templates. JOURNAL OF MEDICINAL CHEMISTRY. 41:4466-4474.PMID: 9804686
-
1998Design and synthesis of a series of potent and orally bioavailable noncovalent thrombin inhibitors that utilize nonbasic groups in the P1 position. JOURNAL OF MEDICINAL CHEMISTRY. 41:3210-3219.PMID: 9703466
-
1998C6 modification of the pyridinone core of thrombin inhibitor L-374,087 as a means of enhancing its oral absorption. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. 8:1719-1724.PMID: 9873422
-
1998L-374,087, an efficacious, orally bioavailable, pyridinone acetamide thrombin inhibitor. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. 8:817-822.PMID: 9871547
-
1998Assessment of thrombin inhibitor efficacy in a novel rabbit model of simultaneous arterial and venous thrombosis. THROMBOSIS AND HAEMOSTASIS. 79:656-662.PMID: 9531058
-
1998Characterization of the two-step pathway for inhibition of thrombin by alpha-ketoamide transition state analogs. JOURNAL OF BIOLOGICAL CHEMISTRY. 273:4843-4854.PMID: 9478925
-
1998Discovery and development of the novel potent orally active thrombin inhibitor N-(9-hydroxy-9-fluorenecarboxy)prolyl trans-4-aminocyclohexylmethyl amide (L-372,460): Coapplication of structure-based design and rapid multiple analogue synthesis on solid support. JOURNAL OF MEDICINAL CHEMISTRY. 41:401-406.PMID: 9464370
-
1998Novel anticoagulants based an direct inhibition of thrombin and factor Xa. CORONARY ARTERY DISEASE. 9:75-81.PMID: 9647407
-
1997Discovery of a novel, selective, and orally bioavailable class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position. JOURNAL OF MEDICINAL CHEMISTRY. 40:3726-3733.PMID: 9371237
-
1997Synthesis of a series of potent and orally bioavailable thrombin inhibitors that utilize 3,3-disubstituted propionic acid derivatives in the P-3 position. JOURNAL OF MEDICINAL CHEMISTRY. 40:3687-3693.PMID: 9357536
-
1997Potent noncovalent thrombin inhibitors that utilize the unique amino acid D-dicyclohexylalanine in the P3 position. Implications on oral bioavailability and antithrombotic efficacy. JOURNAL OF MEDICINAL CHEMISTRY. 40:1565-1569.PMID: 9171866
-
1995
-
1995VAMPIRE BAT SALIVARY PLASMINOGEN-ACTIVATOR EVOKES MINIMAL BLEEDING RELATIVE TO TISSUE-TYPE PLASMINOGEN-ACTIVATOR AS ASSESSED BY A RABBIT CUTICLE BLEEDING-TIME MODEL. THROMBOSIS AND HAEMOSTASIS. 73:478-483.PMID: 7545321
-
1995HUMAN ERYTHROLEUKEMIC (HEL) CELLS EXPRESS A PLATELET P2T-LIKE ADP RECEPTOR. THROMBOSIS RESEARCH. 77:235-247.PMID: 7740516
-
1993THE SEARCH FOR THE IDEAL THROMBOLYTIC AGENT - MAXIMIZE THE BENEFIT AND MINIMIZE THE RISK. TOXICOLOGIC PATHOLOGY. 21:190-198.PMID: 8210941
-
1993VAMPIRE BAT SALIVARY PLASMINOGEN-ACTIVATOR. PROTEOLYTIC ENZYMES IN COAGULATION, FIBRINOLYSIS, AND COMPLEMENT ACTIVATION, PART B. 233-249.PMID: 8271956
-
1992HEPARIN ENHANCES ACTIVE SITE-DEPENDENT BINDING OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR TO ENDOTHELIAL-CELLS. BLOOD. 80:1486-1495.PMID: 1520875
-
1992VAMPIRE BAT SALIVARY PLASMINOGEN-ACTIVATOR EXHIBITS A STRICT AND FASTIDIOUS REQUIREMENT FOR POLYMERIC FIBRIN AS ITS COFACTOR, UNLIKE HUMAN TISSUE-TYPE PLASMINOGEN-ACTIVATOR - A KINETIC-ANALYSIS. JOURNAL OF BIOLOGICAL CHEMISTRY. 267:17726-17731.PMID: 1387641
-
1992VAMPIRE BAT SALIVARY PLASMINOGEN-ACTIVATOR PROMOTES ROBUST LYSIS OF PLASMA CLOTS IN A PLASMA MILIEU WITHOUT CAUSING FLUID PHASE PLASMINOGEN ACTIVATION. THROMBOSIS AND HAEMOSTASIS. 68:165-169.PMID: 1412162
-
1992VAMPIRE BAT SALIVARY PLASMINOGEN-ACTIVATOR PROMOTES RAPID AND SUSTAINED REPERFUSION WITHOUT CONCOMITANT SYSTEMIC PLASMINOGEN ACTIVATION IN A CANINE MODEL OF ARTERIAL THROMBOSIS. ARTERIOSCLEROSIS AND THROMBOSIS. 12:212-221.PMID: 1371932
-
1991
-
1991COMBINATORIAL MUTAGENESIS OF THE REACTIVE SITE REGION IN PLASMINOGEN-ACTIVATOR INHIBITOR-I. JOURNAL OF BIOLOGICAL CHEMISTRY. 266:8495-8500.PMID: 2022663
-
1990THE PHARMACOKINETICS OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 IN THE RABBIT. BLOOD. 76:1514-1520.PMID: 2207327
-
1990PURIFICATION AND CHARACTERIZATION OF HUMAN PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-I EXPRESSED IN SACCHAROMYCES-CEREVISIAE. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS. 278:467-474.PMID: 2183723
-
1989ISOLATION, CHARACTERIZATION, AND CDNA CLONING OF A VAMPIRE BAT SALIVARY PLASMINOGEN-ACTIVATOR. JOURNAL OF BIOLOGICAL CHEMISTRY. 264:17947-17952.PMID: 2509450
-
1968BIOSYNTHESIS OF GLYCOSAMINOGLYCANS (MUCOPOLYSACCHARIDES) IN HUMAN LEUKOCYTES. BIOCHIMICA ET BIOPHYSICA ACTA. 165:309-&.PMID: 4243121
-
1967ANALYSIS OF AORTIC GLYCOSAMINOGLYCANS FROM VARIOUS ANIMAL SPECIES BY CPC-CELLULOSE COLUMN PROCEDURES. JOURNAL OF ATHEROSCLEROSIS RESEARCH. 7:283-&.PMID: 6036101
-
1965AN ION-EXCHANGE COLUMN CHROMATOGRAPHIC METHOD FOR SEPARATION AND QUANTITATIVE ANALYSIS OF NEUTRAL MONOSACCHARIDES. ANALYTICAL BIOCHEMISTRY. 13:177-&.PMID: 5863677
Research
principal investigator on
Background
Full Name
- Stephen J Gardell, PhD
Education
- Cornell University, Graduate School of Medical Sciences, NY, NY
Contact
primary email
- Research.Institute@AdventHealth.com