Lawrence H. Young, M.D. Professor of Internal Medicine and Cellular and Molecular Physiology

B.A., Brown University, 1976; M.D., Yale University, 1980; Intern and Resident in Internal Medicine, Yale New Haven Hospital, 1980-1983; Post-doctoral Fellow in Cardiology, Yale University, 1983-1986; joined Yale faculty, 1986.

Research Interests: Cellular and Molecular Mechanisms of Metabolic Adaptation to Myocardial Ischemia; Clinical Heart Disease in Diabetes.

Our laboratory is studying the cellular and molecular mechanisms responsible for the metabolic adaptation to myocardial ischemia, recently focusing on the AMP-activated protein kinase signaling pathway. Combining clinically relevant experimental models of ischemia with cellular and molecular techniques, we are interested in the cardioprotective action of AMPK in the heart, the upstream mechanisms of AMPK activation and its downstream interaction with other signaling pathways, as well as the discovery of novel AMPK targets. The laboratory is also studying the regulation of glucose transport in the heart, including the molecular mechanisms responsible for GLUT4 translocation within the myocardial cell.  The goal of this research is to develop novel strategies to protect the heart against injury during myocardial ischemia.

 
Our clinical research group has a long-standing interest in heart disease in patients with diabetes and strives to translate fundamental research to the clinical arena. Our group directs multi-center clinical studies in both patients with diabetes and in non-diabetic patients with insulin resistance. The Yale-based multi-center Detection of Ischemia in Asymptomatic Diabetics (DIAD) study aims to identify new approaches to identify asymptomatic coronary artery disease in patients with type 2 diabetes. The Yale-based Insulin-Resistance in Stroke (IRIS) trial is an NIH-sponsored multi-center trial testing the novel hypothesis that treatment of insulin-resistance will prevent heart attack and recurrent stroke in non-diabetic insulin-resistant patients.





Young LH. AMP-activated protein kinase conducts the ischemic stress response orchestra, Circulation, 117 (6), 832-40, 2008.

Miller EJ, Li J, Leng L, McDonald C, Atsumi T, Bucala R, Young LH. Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart. Nature, 451 (7178), 578-82, 2008.

Miller EJ, Li J, Sinusas KM, Holman GD, Young LH. Infusion of a biotinylated bis-glucose photolabel: a new method to quantify cell surface GLUT4 in the intact mouse heart.  American Journal of Physiology. 292 (6), E1922-8, 2007.

Baron S, Li J, Russell RR, Neumann D, Miller EJ, Tuerk R, Wallimann T, Hurley R, Witters LA, Young LH. Dual mechanisms regulating AMPK kinase action in the ischemic heart. Circulation Research 2005;96:337-345.



Li J, Miller EJ, Ninomiya-Tsuji J, Russell RR, Young LH. AMPK activates p38 MAP kinase by increasing its recruitment to TAB1 in the ischemic heart. Circulation Research 2005;97:872-879.



Russell RR, Li J, Coven D, Pypaert M, Zechner C, Palmeri M, Giordano F, Mu J, Birnbaum M, Young LH. AMP-activated protein kinase mediates ischemic glucose uptake and prevents post-ischemic cardiac dysfunction, apoptosis and injury. J Clin Invest 2004;114:495-503 (featured article with editorial comment) .


Bax JJ, Young LH, Frye RL, Bonow RO, Steinberg HO, Barrett EJ. Screening for coronary artery disease in patients with diabetes. Diabetes Care, 30 (10), 2729-36, 2007.

Wackers FJ, Young LH, Inzucchi SE, Chyun DA, Davey JA, Barrett EJ, Taillefer R, Wittlin SD, Heller GV, Filipchuk N, Engel S, Ratner RE, Iskandrian AE. Detection of silent myocardial ischemia in asymptomatic diabetic subjects: The DIAD study. Diabetes Care 2004;27:1954-1961.



Johnson B, Nesto R, Pfeifer M, Slater W, Vinik A, Chyun D, Law G, Wackers F, Young LH. Cardiac abnormalities in diabetic patients with neuropathy: effects of aldose reductase inhibitor administration. Diabetes Care 2004;27:448-454.


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Last modified:Wednesday, 09-Apr-2008 12:57:53 EDT (PL).