My passion is multidisciplinary biomedical research aimed at unraveling the molecular mechanisms of cardiovascular and metabolic disease. The changing trends in the pharmaceutical industry have made research organizations such as Sanford-Burnham one of the most promising sources of ideas for the medicines of tomorrow. I joined the faculty to help the institute achieve its stated goal of excelling in early stage drug discovery and translational research.
Dr. Gardell directs an array of translational research technology platforms that facilitate the adancement of basic scientific discoveries.
Dr. Gardell received his Ph.D. degree in Biochemistry from the Cornell University Graduate School of Medical Sciences.
View All Publications
Cardiovascular drug discovery in the academic setting: building infrastructure, harnessing strengths, and seeking synergies.
Gardell SJ, Roth GP, Kelly DP
J Cardiovasc Transl Res. 2010 Oct;3(5):431-7
Effect of the small molecule plasminogen activator inhibitor-1 (PAI-1) inhibitor, PAI-749, in clinical models of fibrinolysis.
Lucking AJ, Visvanathan A, Philippou H, Fraser S, Grant PJ, Connolly TM, Gardell SJ, Feuerstein GZ, Fox KA, Booth NA, Newby DE
J Thromb Haemost. 2010 Jun;8(6):1333-9
LXR ligand lowers LDL cholesterol in primates, is lipid neutral in hamster, and reduces atherosclerosis in mouse.
Quinet EM, Basso MD, Halpern AR, Yates DW, Steffan RJ, Clerin V, Resmini C, Keith JC, Berrodin TJ, Feingold I, Zhong W, Hartman HB, Evans MJ, Gardell SJ, DiBlasio-Smith E, Mounts WM, LaVallie ER, Wrobel J, Nambi P, Vlasuk GP
J Lipid Res. 2009 Dec;50(12):2358-70
Activation of farnesoid X receptor prevents atherosclerotic lesion formation in LDLR-/- and apoE-/- mice.
Hartman HB, Gardell SJ, Petucci CJ, Wang S, Krueger JA, Evans MJ
J Lipid Res. 2009 Jun;50(6):1090-100
Enhanced clearance of Abeta in brain by sustaining the plasmin proteolysis cascade.
Jacobsen JS, Comery TA, Martone RL, Elokdah H, Crandall DL, Oganesian A, Aschmies S, Kirksey Y, Gonzales C, Xu J, Zhou H, Atchison K, Wagner E, Zaleska MM, Das I, Arias RL, Bard J, Riddell D, Gardell SJ, Abou-Gharbia M, Robichaud A, Magolda R, Vlasuk GP, Bjornsson T, Reinhart PH, Pangalos MN
Proc Natl Acad Sci U S A. 2008 Jun 24;105(25):8754-9
Neutralization of plasminogen activator inhibitor I (PAI-1) by the synthetic antagonist PAI-749 via a dual mechanism of action.
Gardell SJ, Krueger JA, Antrilli TA, Elokdah H, Mayer S, Orcutt SJ, Crandall DL, Vlasuk GP
Mol Pharmacol. 2007 Oct;72(4):897-906
Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1.
Li YM, Xu M, Lai MT, Huang Q, Castro JL, DiMuzio-Mower J, Harrison T, Lellis C, Nadin A, Neduvelil JG, Register RB, Sardana MK, Shearman MS, Smith AL, Shi XP, Yin KC, Shafer JA, Gardell SJ
Nature. 2000 Jun 8;405(6787):689-94
Presenilin 1 is linked with gamma-secretase activity in the detergent solubilized state.
Li YM, Lai MT, Xu M, Huang Q, DiMuzio-Mower J, Sardana MK, Shi XP, Yin KC, Shafer JA, Gardell SJ
Proc Natl Acad Sci U S A. 2000 May 23;97(11):6138-43
Isolation, characterization, and cDNA cloning of a vampire bat salivary plasminogen activator.
Gardell SJ, Duong LT, Diehl RE, York JD, Hare TR, Register RB, Jacobs JW, Dixon RA, Friedman PA
J Biol Chem. 1989 Oct 25;264(30):17947-52
Site-directed mutagenesis shows that tyrosine 248 of carboxypeptidase A does not play a crucial role in catalysis.
Gardell SJ, Craik CS, Hilvert D, Urdea MS, Rutter WJ
Nature. 1985 Oct 10-16;317(6037):551-5
Stephen Gardell's Research Focus
Cardiovascular Diseases, Atherosclerosis, Heart Disease, Type 2 Diabetes, Cardiomyopathies
Dr. Stephen Gardell aims to use his 20 years of experience in the pharmaceutical industry to drive the advancement of basic research discoveries to realize their potential therapeutic utility. In particular, he oversees the development and operation of several advanced technology core facilities: Metabolomics, Cardiometabolic Phenotyping, Histopathology, Cellular Imaging and the Vivarium at Lake Nona. His personal laboratory pursuits are centered around the role of LXR, a nuclear hormone receptor, and its endogenous oxysterol ligands in cardiovascular disease.
Stephen Gardell's Research Report
LXR agonists are known to exert remarkable efficacy in murine models of atherosclerosis. The current dogma is that efficacy arises from stimulation of reverse cholesterol transport whereby cholesterol is exported from the vessel wall (accumulated in “foam cells”) and transferred back to the liver where it is eliminated. This is probably not the whole story. The experiments in my laboratory are aimed at achieving a deeper understanding about the LXR-regulated mechanisms that operate at/in the vessel wall that serve to impede the development of atherosclerotic lesions.
About Stephen Gardell
Stephen Gardell, Ph.D., received a B.S. degree in Biology from Boston College and a Ph.D. degree in Biochemistry from the Cornell University Graduate School of Medical Sciences. He performed post-doctoral studies at the University of California, San Francisco (UCSF) in the laboratory of Dr. William J. Rutter. Dr. Gardell joined Merck Research Laboratories (West Point, PA) in 1987, where he studied thrombosis and Alzheimer’s disease. His investigations of the secretases provided key insight into the pathophysiology of Alzheimer’s disease. In 2001, Dr. Gardell became the Director of Obesity Research at Bayer Research (West Haven, CT), where he pursued weight loss strategies involving appetite control and energy expenditure. In 2004, Dr. Gardell became Assistant Vice President, Cardiovascular Discovery Research at Wyeth where he directed programs in atherosclerosis, heart failure, thrombosis and arrhythmias. In 2009, Dr. Gardell joined Sanford-Burnham Medical Research Institute at Lake Nona, where he is the Director of Translational Research Resources and Associate Professor.