Lawrence Young

Bio Profile

Lawrence Howard Young, MD

Professor of Medicine (Cardiology) and of Cellular And Molecular Physiology

Vice-Chair, Department of Medicine

Research Interests

AMP-Activated Protein Kinases; Apoptosis; Cell Survival; Diabetes Mellitus; Glucose Transporter Type 4; Insulin Resistance; Myocardial Ischemia

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Young Lab


Key areas of our research are the molecular & cellular mechanisms regulating heart (metabolism in cv disease), autocrine-paracrine pathways (modulating cardiac cell signaling and function), and metabolic signaling pathways in atrial fibrillation.  Processes under investigation include: regulation of heart metabolism/function; AMPK protection against solid organ ischemia; JNK pathway in reperfusion injury; cardiac autocrine/paracrine factors; MIF CD74 signaling; novel myocyte autocrine proteins; atrial fibrillation; and LKB1 role in cardiac growth and remodeling.

Publications

Young LH, Viscoli CM, Curtis JP, Inzucchi SE, Schwartz GG, Lovejoy AM, Furie KL, Gorman MJ, Conwit R, Abbott JD, Jacoby DL, Kolansky DM, Pfau SE, Ling FS, Kernan WN, IRIS Investigators.: Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack: Effects of Pioglitazone in Patients With Insulin Resistance Without Diabetes Mellitus. Circulation. 2017 May 16; 2017 Feb 28. PMID: 28246237

Chizinga M, Rudkovskaia AA, Henderson K, Pollak J, Garcia-Tsao G, Young LH, Fares WH: Pulmonary Hypertension Prevalence and Prognosis in a Cohort of Patients with Hereditary Hemorrhagic Telangiectasia Undergoing Embolization of pAVMs. Am J Respir Crit Care Med. 2017 Apr 4; 2017 Apr 4. PMID: 28375020

Inzucchi SE, Viscoli CM, Young LH, Furie KL, Gorman M, Lovejoy AM, Dagogo-Jack S, Ismail-Beigi F, Korytkowski MT, Pratley RE, Schwartz GG, Kernan WN, IRIS Trial Investigators.: Response to Comment on Inzucchi et al. Pioglitazone Prevents Diabetes in Patients With Insulin Resistance and Cerebrovascular Disease. Diabetes Care 2016;39:1684-1692. Diabetes Care. 2017 Apr. PMID: 28325804

Viscoli CM, Inzucchi SE, Young LH, Insogna KL, Conwit R, Furie KL, Gorman M, Kelly MA, Lovejoy AM, Kernan WN, IRIS Trial Investigators.: Pioglitazone and Risk for Bone Fracture: Safety Data From a Randomized Clinical Trial. J Clin Endocrinol Metab. 2017 Mar 1. PMID: 27935736

Ola R, Dubrac A, Han J, Zhang F, Fang JS, Larrivée B, Lee M, Urarte AA, Kraehling JR, Genet G, Hirschi KK, Sessa WC, Canals FV, Graupera M, Yan M, Young LH, Oh PS, Eichmann A: PI3 kinase inhibition improves vascular malformations in mouse models of hereditary haemorrhagic telangiectasia. Nat Commun. 2016 Nov 29; 2016 Nov 29. PMID: 27897192

Inzucchi SE, Viscoli CM, Young LH, Furie KL, Gorman M, Lovejoy AM, Dagogo-Jack S, Ismail-Beigi F, Korytkowski MT, Pratley RE, Schwartz GG, Kernan WN, IRIS Trial Investigators.: Pioglitazone Prevents Diabetes in Patients With Insulin Resistance and Cerebrovascular Disease. Diabetes Care. 2016 Oct; 2016 Jul 27. PMID: 27465265

Bartulos O, Zhuang ZW, Huang Y, Mikush N, Suh C, Bregasi A, Wang L, Chang W, Krause DS, Young LH, Pober JS, Qyang Y: ISL1 cardiovascular progenitor cells for cardiac repair after myocardial infarction. JCI Insight. 2016 Jul 7. PMID: 27525311

Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M, Guarino PD, Lovejoy AM, Peduzzi PN, Conwit R, Brass LM, Schwartz GG, Adams HP Jr, Berger L, Carolei A, Clark W, Coull B, Ford GA, Kleindorfer D, O'Leary JR, Parsons MW, Ringleb P, Sen S, Spence JD, Tanne D, Wang D, Winder TR, IRIS Trial Investigators.: Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. N Engl J Med. 2016 Apr 7; 2016 Feb 17. PMID: 26886418

Li N, Hwangbo C, Jaba IM, Zhang J, Papangeli I, Han J, Mikush N, Larrivée B, Eichmann A, Chun HJ, Young LH, Tirziu D: miR-182 Modulates Myocardial Hypertrophic Response Induced by Angiogenesis in Heart. Sci Rep. 2016 Feb 18; 2016 Feb 18. PMID: 26888314

Zaha VG, Qi D, Su KN, Palmeri M, Lee HY, Hu X, Wu X, Shulman GI, Rabinovitch PS, Russell RR 3rd, Young LH: AMPK is critical for mitochondrial function during reperfusion after myocardial ischemia. J Mol Cell Cardiol. 2016 Feb; 2015 Dec 30. PMID: 26746142

Kim GE, Ross JL, Xie C, Su KN, Zaha VG, Wu X, Palmeri M, Ashraf M, Akar JG, Russell KS, Akar FG, Young LH: LKB1 deletion causes early changes in atrial channel expression and electrophysiology prior to atrial fibrillation. Cardiovasc Res. 2015 Oct 1. PMID: 26378152

Qi D, Young LH: AMPK: energy sensor and survival mechanism in the ischemic heart. Trends Endocrinol Metab. 2015 Aug; 2015 Jul 6. PMID: 26160707

Kim GE, Young LH: AMPK and the Atrial Response to Metabolic Inhibition. J Am Coll Cardiol. 2015 Jul 7. PMID: 26139059

Chyun DA, Wackers FJ, Inzucchi SE, Jose P, Weiss C, Davey JA, Heller GV, Iskandrian AE, Young LH, DIAD Investigators.: Autonomic dysfunction independently predicts poor cardiovascular outcomes in asymptomatic individuals with type 2 diabetes in the DIAD study. SAGE Open Med. 2015; 2015 Feb 24. PMID: 26770763

Viscoli CM, Brass LM, Carolei A, Conwit R, Ford GA, Furie KL, Gorman M, Guarino PD, Inzucchi SE, Lovejoy AM, Parsons MW, Peduzzi PN, Ringleb PA, Schwartz GG, Spence JD, Tanne D, Young LH, Kernan WN, IRIS Trial investigators.: Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: rationale and design of the Insulin Resistance Intervention after Stroke Trial. Am Heart J. 2014 Dec; 2014 Jul 28. PMID: 25458644

Young LH, Henderson KJ, White RI, Garcia-Tsao G: Bevacizumab: finding its niche in the treatment of heart failure secondary to liver vascular malformations in hereditary hemorrhagic telangiectasia. Hepatology. 2013 Jul; 2013 May 31. PMID: 23686865

Jaba IM, Zhuang ZW, Li N, Jiang Y, Martin KA, Sinusas AJ, Papademetris X, Simons M, Sessa WC, Young LH, Tirziu D: NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth. J Clin Invest. 2013 Apr. PMID: 23454748

Shugrue CA, Alexandre M, Diaz de Villalvilla A, Kolodecik TR, Young LH, Gorelick FS, Thrower EC: Cerulein hyperstimulation decreases AMP-activated protein kinase levels at the site of maximal zymogen activation. Am J Physiol Gastrointest Liver Physiol. 2012 Sep 15; 2012 Jul 19. PMID: 22821946

Zaha VG, Young LH: AMP-activated protein kinase regulation and biological actions in the heart. Circ Res. 2012 Aug 31. PMID: 22935535

Tandon S, Wackers FJ, Inzucchi SE, Bansal S, Staib LH, Chyun DA, Davey JA, Young LH, DIAD Investigators.: Gender-based divergence of cardiovascular outcomes in asymptomatic patients with type 2 diabetes: results from the DIAD study. Diab Vasc Dis Res. 2012 Apr; 2012 Jan 6. PMID: 22228772

Kim AS, Miller EJ, Wright TM, Li J, Qi D, Atsina K, Zaha V, Sakamoto K, Young LH: A small molecule AMPK activator protects the heart against ischemia-reperfusion injury. J Mol Cell Cardiol. 2011 Jul; 2011 Mar 29. PMID: 21402077

Zhang L, Jouret F, Rinehart J, Sfakianos J, Mellman I, Lifton RP, Young LH, Caplan MJ: AMP-activated protein kinase (AMPK) activation and glycogen synthase kinase-3β (GSK-3β) inhibition induce Ca2+-independent deposition of tight junction components at the plasma membrane. J Biol Chem. 2011 May 13; 2011 Mar 7. PMID: 21383016

Bansal S, Wackers FJ, Inzucchi SE, Chyun DA, Davey JA, Staib LH, Young LH, DIAD Study Investigators.: Five-year outcomes in high-risk participants in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study: a post hoc analysis. Diabetes Care. 2011 Jan; 2010 Oct 7. PMID: 20929989

Qi D, Hu X, Wu X, Merk M, Leng L, Bucala R, Young LH: Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion. J Clin Invest. 2009 Dec; 2009 Nov 16. PMID: 19920350

Young LH: A crystallized view of AMPK activation. Cell Metab. 2009 Jul. PMID: 19583947

Kim AS, Miller EJ, Young LH: AMP-activated protein kinase: a core signalling pathway in the heart. Acta Physiol (Oxf). 2009 May; 2009 Feb 23. PMID: 19239414

Young LH, Wackers FJ, Chyun DA, Davey JA, Barrett EJ, Taillefer R, Heller GV, Iskandrian AE, Wittlin SD, Filipchuk N, Ratner RE, Inzucchi SE, DIAD Investigators.: Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA. 2009 Apr 15. PMID: 19366774

Kernan WN, Viscoli CM, Demarco D, Mendes B, Shrauger K, Schindler JL, McVeety JC, Sicklick A, Moalli D, Greco P, Bravata DM, Eisen S, Resor L, Sena K, Story D, Brass LM, Furie KL, Gutmann L, Hinnau E, Gorman M, Lovejoy AM, Inzucchi SE, Young LH, Horwitz RI, IRIS Trial Investigators.: Boosting enrollment in neurology trials with Local Identification and Outreach Networks (LIONs). Neurology. 2009 Apr 14. PMID: 19365056

Young LH: AMP-activated protein kinase conducts the ischemic stress response orchestra. Circulation. 2008 Feb 12. PMID: 18268160

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. 2008 Jan 31. PMID: 18235500

Wackers FJ, Chyun DA, Young LH, Heller GV, Iskandrian AE, Davey JA, Barrett EJ, Taillefer R, Wittlin SD, Filipchuk N, Ratner RE, Inzucchi SE, Detection of Ischemia in Asymptomatic Diabetics (DIAD) Investigators.: Resolution of asymptomatic myocardial ischemia in patients with type 2 diabetes in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study. Diabetes Care. 2007 Nov; 2007 Aug 6. PMID: 17682123

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. Am J Physiol Endocrinol Metab. 2007 Jun; 2007 Mar 6. PMID: 17341550

Reznick RM, Zong H, Li J, Morino K, Moore IK, Yu HJ, Liu ZX, Dong J, Mustard KJ, Hawley SA, Befroy D, Pypaert M, Hardie DG, Young LH, Shulman GI: Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis. Cell Metab. 2007 Feb. PMID: 17276357

Chyun DA, Young LH: Diabetes mellitus and cardiovascular disease. Nurs Clin North Am. 2006 Dec. PMID: 17059982

Zhang L, Li J, Young LH, Caplan MJ: AMP-activated protein kinase regulates the assembly of epithelial tight junctions. Proc Natl Acad Sci U S A. 2006 Nov 14; 2006 Nov 6. PMID: 17088526

Li J, Coven DL, Miller EJ, Hu X, Young ME, Carling D, Sinusas AJ, Young LH: Activation of AMPK alpha- and gamma-isoform complexes in the intact ischemic rat heart. Am J Physiol Heart Circ Physiol. 2006 Oct; 2006 Apr 28. PMID: 16648175

Li J, Miller EJ, Ninomiya-Tsuji J, Russell RR 3rd, Young LH: AMP-activated protein kinase activates p38 mitogen-activated protein kinase by increasing recruitment of p38 MAPK to TAB1 in the ischemic heart. Circ Res. 2005 Oct 28; 2005 Sep 22. PMID: 16179588

Young LH, Li J, Baron SJ, Russell RR: AMP-activated protein kinase: a key stress signaling pathway in the heart. Trends Cardiovasc Med. 2005 Apr. PMID: 16039971

Baron SJ, Li J, Russell RR 3rd, Neumann D, Miller EJ, Tuerk R, Wallimann T, Hurley RL, Witters LA, Young LH: Dual mechanisms regulating AMPK kinase action in the ischemic heart. Circ Res. 2005 Feb 18; 2005 Jan 13. PMID: 15653571

Li J, Hu X, Selvakumar P, Russell RR 3rd, Cushman SW, Holman GD, Young LH: Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle. Am J Physiol Endocrinol Metab. 2004 Nov; 2004 Jul 20. PMID: 15265762

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 Ischemia in Asymptomatic Diabetics Investigators.: Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD study. Diabetes Care. 2004 Aug. PMID: 15277423

Russell RR 3rd, Li J, Coven DL, Pypaert M, Zechner C, Palmeri M, Giordano FJ, Mu J, Birnbaum MJ, Young LH: AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. J Clin Invest. 2004 Aug. PMID: 15314686

Huang Y, Hickey RP, Yeh JL, Liu D, Dadak A, Young LH, Johnson RS, Giordano FJ: Cardiac myocyte-specific HIF-1alpha deletion alters vascularization, energy availability, calcium flux, and contractility in the normoxic heart. FASEB J. 2004 Jul; 2004 May 7. PMID: 15132980

Young LH: Insulin resistance and the effects of thiazolidinediones on cardiac metabolism. Am J Med. 2003 Dec 8. PMID: 14678870

Coven DL, Hu X, Cong L, Bergeron R, Shulman GI, Hardie DG, Young LH: Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise. Am J Physiol Endocrinol Metab. 2003 Sep; 2003 May 20. PMID: 12759223

Young LH, Jose P, Chyun D: Diagnosis of CAD in patients with diabetes: who to evaluate. Curr Diab Rep. 2003 Feb. PMID: 12643142

Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ, Shulman GI: AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci U S A. 2002 Dec 10; 2002 Nov 20. PMID: 12444247

Chyun D, Vaccarino V, Murillo J, Young LH, Krumholz HM: Cardiac outcomes after myocardial infarction in elderly patients with diabetes mellitus. Am J Crit Care. 2002 Nov. PMID: 12425401

Chyun D, Vaccarino V, Murillo J, Young LH, Krumholz HM: Acute myocardial infarction in the elderly with diabetes. Heart Lung. 2002 Sep-Oct. PMID: 12487011

Shi CQ, Young LH, Daher E, DiBella EV, Liu YH, Heller EN, Zoghbi S, Wackers FJ, Soufer R, Sinusas AJ: Correlation of myocardial p-(123)I-iodophenylpentadecanoic acid retention with (18)F-FDG accumulation during experimental low-flow ischemia. J Nucl Med. 2002 Mar. PMID: 11884504

Bergeron R, Ren JM, Cadman KS, Moore IK, Perret P, Pypaert M, Young LH, Semenkovich CF, Shulman GI: Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis. Am J Physiol Endocrinol Metab. 2001 Dec. PMID: 11701451

Russell RR 3rd, Chyun D, Song S, Sherwin RS, Tamborlane WV, Lee FA, Pfeifer MA, Rife F, Wackers FJ, Young LH: Cardiac responses to insulin-induced hypoglycemia in nondiabetic and intensively treated type 1 diabetic patients. Am J Physiol Endocrinol Metab. 2001 Nov. PMID: 11595660

Bergeron R, Previs SF, Cline GW, Perret P, Russell RR 3rd, Young LH, Shulman GI: Effect of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats. Diabetes. 2001 May. PMID: 11334411

Young LH, Coven DL, Russell RR 3rd: Cellular and molecular regulation of cardiac glucose transport. J Nucl Cardiol. 2000 May-Jun. PMID: 10888399

Russell RR 3rd, Bergeron R, Shulman GI, Young LH: Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR. Am J Physiol. 1999 Aug. PMID: 10444490

Young LH, Russell RR 3rd, Yin R, Caplan MJ, Ren J, Bergeron R, Shulman GI, Sinusas AJ: Regulation of myocardial glucose uptake and transport during ischemia and energetic stress. Am J Cardiol. 1999 Jun 17. PMID: 10750583

Bergeron R, Russell RR 3rd, Young LH, Ren JM, Marcucci M, Lee A, Shulman GI: Effect of AMPK activation on muscle glucose metabolism in conscious rats. Am J Physiol. 1999 May. PMID: 10329989

Young LH, Renfu Y, Hu X, Chong S, Hasan S, Jacob R, Sherwin RS: Insulin-like growth factor I stimulates cardiac myosin heavy chain and actin synthesis in the awake rat. Am J Physiol. 1999 Jan. PMID: 9886960

Russell RR 3rd, Yin R, Caplan MJ, Hu X, Ren J, Shulman GI, Sinusas AJ, Young LH: Additive effects of hyperinsulinemia and ischemia on myocardial GLUT1 and GLUT4 translocation in vivo. Circulation. 1998 Nov 17. PMID: 9815873

Young LH, Renfu Y, Russell R, Hu X, Caplan M, Ren J, Shulman GI, Sinusas AJ: Low-flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1 glucose transporters to the sarcolemma in vivo. Circulation. 1997 Jan 21. PMID: 9008459

Jacob R, Hu X, Niederstock D, Hasan S, McNulty PH, Sherwin RS, Young LH: IGF-I stimulation of muscle protein synthesis in the awake rat: permissive role of insulin and amino acids. Am J Physiol. 1996 Jan. PMID: 8772474

Shi CQ, Sinusas AJ, Dione DP, Singer MJ, Young LH, Heller EN, Rinker BD, Wackers FJ, Zaret BL: Technetium-99m-nitroimidazole (BMS181321): a positive imaging agent for detecting myocardial ischemia. J Nucl Med. 1995 Jun. PMID: 7769431

Young LH, Stirewalt W, McNulty PH, Revkin JH, Barrett EJ: Effect of insulin on rat heart and skeletal muscle phenylalanyl-tRNA labeling and protein synthesis in vivo. Am J Physiol. 1994 Aug. PMID: 8074214

McNulty PH, Young LH, Barrett EJ: Response of rat heart and skeletal muscle protein in vivo to insulin and amino acid infusion. Am J Physiol. 1993 Jun. PMID: 8333520

Hoch DH, Salazar AM, Cabin HS, Young LH: Equine arch vessel anomaly associated with coarctation of the aorta. Chest. 1992 Aug. PMID: 1643963

Young LH, Dahl DM, Rauner D, Barrett EJ: Physiological hyperinsulinemia inhibits myocardial protein degradation in vivo in the canine heart. Circ Res. 1992 Aug. PMID: 1628395

Young LH, McNulty PH, Morgan C, Deckelbaum LI, Zaret BL, Barrett EJ: Myocardial protein turnover in patients with coronary artery disease. Effect of branched chain amino acid infusion. J Clin Invest. 1991 Feb. PMID: 1991838

Revkin JH, Young LH, Stirewalt WS, Dahl DM, Gelfand RA, Zaret BL, Barrett EJ: In vivo measurement of myocardial protein turnover using an indicator dilution technique. Circ Res. 1990 Oct. PMID: 2208613

Young LH, Jaffe CC, Revkin JH, McNulty PH, Cleman M: Metabolic and functional effects of perfluorocarbon distal perfusion during coronary angioplasty. Am J Cardiol. 1990 Apr 15. PMID: 2327360

Barrett EJ, Schwartz RG, Young LH, Jacob R, Zaret BL: Effect of chronic diabetes on myocardial fuel metabolism and insulin sensitivity. Diabetes. 1988 Jul. PMID: 3290011

Barrett EJ, Revkin JH, Young LH, Zaret BL, Jacob R, Gelfand RA: An isotopic method for measurement of muscle protein synthesis and degradation in vivo. Biochem J. 1987 Jul 1. PMID: 3663148