Adam Lauver, Ph.D.
- Cardiovascular Staff, Drug Discovery and Receptor Faculty
Pharmacology & Toxicology
B336B Life Sciences
1355 Bogue Street
East Lansing, MI 48823
Fields of Interest: Cardiovascular diseases and drug discovery.
Lauver Lab Website: http://www.lauverlab.org
- 1997-2001, B.S. Biology, Pennsylvania State University
- 2002-2007, Ph.D. Pharmacology, University of Michigan
- 2007-2011, Postdoctoral Fellow, University of Michigan
- 2011-2015, Research Investigator, University of Michigan
- 2015-2016, Research Assistant Professor, University of Michigan
- 2016-Present, Assistant Professor, Michigan State University
Biography & Current Research
Our laboratory focuses on the discovery and development on novel therapeutic agents for the treatment of cardiovascular diseases. We employ in vivo models of thrombosis, reperfusion injury and arrhythmia to gain a better understanding of the mechanisms by which these diseases occur while also identifying exciting new targets for treatment. More recently we have discovered that a class of drugs used for the treatment of erectile dysfunction have potential utility in the prevention of contrast-induced acute kidney injury.
Prevention of Contrast-induced Acute Kidney Injury
Contrast-induced acute kidney injury (CIAKI) is a complex syndrome of acute nephropathy occurring within 48 hours of exposure to intravascular iodinated contrast media. CIAKI is associated with an increased risk of adverse cardiovascular events, prolonged hospitalization, and short- and long-term mortality. The pathophysiology of CIAKI is poorly understood and little is known about the underlying cellular mechanisms. With the increasing use of contrast media in both diagnostic and interventional procedures, CIAKI has become the third leading cause of hospital-acquired AKI. The incidence of CIAKI remains high despite the introduction of newer and safer contrast media.
Although the exact mechanism of contrast-induced renal injury is unknown, vasoconstriction of the peritubular capillaries is thought to be an important component. Consequently, our current studies seek to investigate whether a class of vasodilators (Phosphodiesterase Type 5 inhibitors) which are used in the treatment of erectile dysfunction might also protect the kidney from contrast-induced damage.
Development of a Novel Conjugate of Clopidogrel
Clopidogrel is an oral antithrombotic prodrug that inhibits the platelet P2Y12 receptor upon bioactivation by members of the cytochrome P450 family. In combination with aspirin, clopidogrel is widely used in dual antiplatelet therapy to treat patients with acute coronary syndromes, especially those receiving percutaneous coronary interventions. Despite its broad use in clinical cardiology, clopidogrel has major limitations including interindividual variability, delayed onset of action, and adverse drug–drug interactions. A large body of evidence indicates that approximately 30% of Caucasians and up to 60%–70% of Asians respond poorly to clopidogrel therapy, in part due to polymorphisms in the CYP450 enzyme responsible for its bioactivation (CYP2C19). As a result, these patients are at increased risk for major adverse cardiovascular events.
In collaboration with a research team at the University of Michigan, we have generated a mixed disulfide conjugate of the active metabolite of clopidogrel with 3-nitropyridine-2-thiol. This conjugate is readily converted to the active metabolite in the presence of glutathione through a thiol disulfide exchange reaction. Our current research is focused on characterizing the speed and effectiveness by which this drug inhibits platelet aggregation and the formation of occlusive thrombi in vivo.
Awards & Achievements
- Rackham Graduate School Travel Award, 2005
- ASPET Board of Publications Trustees Young Scientist Travel Award, 2010
- Frankel Cardiovascular Center Inaugural Grant Award, 2014
Committees & Activities
- Memberships in Professional Societies:
- American Heart Association (2003-Present)
- American Society of Pharmacology and Experimental Therapeutics (2004-Present)
- American Physiological Society (2005-Present)
Zhang H, Lauver DA, Wang H, Sun D, Hollenberg PF, Chen YE, Osawa Y, Eitzman DT. Significant Improvement of Antithrombotic Responses to Clopidogrel by Use of a Novel Conjugate as Revealed in an Arterial Model of Thrombosis. The Journal of Pharmacology and Experimental Therapeutics. 2016 Oct;359(1):11-7.
Lauver DA, Carey EG, Bergin IL, Lucchesi BR, Gurm HS. Sildenafil citrate for prophylaxis of nephropathy in an animal model of contrast-induced acute kidney injury. PLoS One. 2014 Nov 26;9(11):e113598.
Zhang H, Lauver DA, Hollenberg PF. CYP-independent inhibition of platelet aggregation in rabbits by a mixed disulfide conjugate of clopidogrel. Thrombosis and Haemostasis. 2014 Dec 1;112(6):1304-11.
Zhang H, Lauver DA, Lucchesi BR, Hollenberg PF. Formation, reactivity, and antiplatelet activity of mixed disulfide conjugates of clopidogrel. Molecular Pharmacology. April 2013; 83(4):848-856.
Lauver DA, Kaissarian NM, Lucchesi BR. Oral pretreatment with liposomal glutathione attenuates reperfusion injury in rabbit isolated hearts. Journal of Cardiovascular Pharmacology. Mar 2013; 61(3):233-239.