Research

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Leslie B.  Smoot, MD

Leslie Smoot
Department:
Cardiology Research
Hospital Title:
Assistant in Cardiology
Academic Title:
Instructor in Pediatrics, Harvard Medical School
Research Focus Area:
Cardiovascular genetics

Research Overview

Leslie Smoot's research focuses on the genetics of Congenital Cardiovascular Disease. The familial clustering of congenital heart disease (CHD) has long suggested a role for genetic mutations, but the extent to which mutations contribute is poorly defined. In a few cases disease genes have been identified by linkage analysis in extended pedigrees, but the rarity of large, affected families limits the pace of discovery. In contrast, significant progress has been made in transgenic and knockout mouse models of cardiac development, suggesting new candidate genes for human CHD.

As molecular mechanisms underlying cardiovascular development become elucidated, they are likely to have both medical and reproductive implications. With improved surgical palliation of congenital heart disease, caregivers are faced with new challenges associated with childbearing, not the least of which includes recurrence risk. Research performed in this area may help provide individual families with recurrence risks based on genetic rather than empiric data, and may elucidate additional non-cardiac roles for the candidate genes analyzed.

About Leslie Smoot

Dr. Smoot received her MD from the University of Minnesota School of Medicine, followed by a Pediatric Cardiology Fellowship at Children's Hospital, Boston.

Publications

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  1. Cunningham JW, McElhinney DB, Gauvreau K, Bergersen L, Lacro RV, Marshall AC, Smoot L, Lock JE. Outcomes after primary transcatheter therapy in infants and young children with severe bilateral peripheral pulmonary artery stenosis. Circ Cardiovasc Interv. 2013 Aug; 6(4):460-7.
  2. Lage K, Greenway SC, Rosenfeld JA, Wakimoto H, Gorham JM, Segrè AV, Roberts AE, Smoot LB, Pu WT, Pereira AC, Mesquita SM, Tommerup N, Brunak S, Ballif BC, Shaffer LG, Donahoe PK, Daly MJ, Seidman JG, Seidman CE, Larsen LA. Genetic and environmental risk factors in congenital heart disease functionally converge in protein networks driving heart development. Proc Natl Acad Sci U S A. 2012 Aug 28; 109(35):14035-40.
  3. Ford MA, Almond CS, Gauvreau K, Piercey G, Blume ED, Smoot LB, Fynn-Thompson F, Singh TP. Association of graft ischemic time with survival after heart transplant among children in the United States. J Heart Lung Transplant. 2011 Nov; 30(11):1244-9.
  4. Lin AE, Alexander ME, Colan SD, Kerr B, Rauen KA, Noonan J, Baffa J, Hopkins E, Sol-Church K, Limongelli G, Digilio MC, Marino B, Innes AM, Aoki Y, Silberbach M, Delrue MA, White SM, Hamilton RM, O'Connor W, Grossfeld PD, Smoot LB, Padera RF, Gripp KW. Clinical, pathological, and molecular analyses of cardiovascular abnormalities in Costello syndrome: a Ras/MAPK pathway syndrome. Am J Med Genet A. 2011 Mar; 155A(3):486-507.
  5. Morell E, Cheng H, Scheurer M, Smoot L, Wolfe J, Beke D, Blume E. Patterns of End-of-Life Care in Children with Advanced Heart Disease (747). J Pain Symptom Manage. 2011 Jan; 41(1):301.
  6. Olive M, Harten I, Mitchell R, Beers JK, Djabali K, Cao K, Erdos MR, Blair C, Funke B, Smoot L, Gerhard-Herman M, Machan JT, Kutys R, Virmani R, Collins FS, Wight TN, Nabel EG, Gordon LB. Cardiovascular pathology in Hutchinson-Gilford progeria: correlation with the vascular pathology of aging. Arterioscler Thromb Vasc Biol. 2010 Nov; 30(11):2301-9.
  7. Silva JN, Canter CE, Singh TP, Gauvreau K, Piercey GE, Berul CI, Smoot LB, Blume ED, Fynn-Thompson F, Almond CS. Outcomes of heart transplantation using donor hearts from infants with sudden infant death syndrome. J Heart Lung Transplant. 2010 Nov; 29(11):1226-30.
  8. Lage K, Møllgård K, Greenway S, Wakimoto H, Gorham JM, Workman CT, Bendsen E, Hansen NT, Rigina O, Roque FS, Wiese C, Christoffels VM, Roberts AE, Smoot LB, Pu WT, Donahoe PK, Tommerup N, Brunak S, Seidman CE, Seidman JG, Larsen LA. Dissecting spatio-temporal protein networks driving human heart development and related disorders. Mol Syst Biol. 2010 Jun 22; 6:381.
  9. Almond CS, Gauvreau K, Thiagarajan RR, Piercey GE, Blume ED, Smoot LB, Fynn-Thompson F, Singh TP. Impact of ABO-incompatible listing on wait-list outcomes among infants listed for heart transplantation in the United States: a propensity analysis. Circulation. 2010 May 4; 121(17):1926-33.
  10. Obler D, Wu BL, Lip V, Estrella E, Keck S, Haggan C, Semigran M, Smoot LB. Familial dilated cardiomyopathy secondary to dystrophin splice site mutation. J Card Fail. 2010 Mar; 16(3):194-9.
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  12. Smoot LB, Obler D, McElhinney DB, Boardman K, Wu BL, Lip V, Mullen MP. Clinical features of pulmonary arterial hypertension in young people with an ALK1 mutation and hereditary haemorrhagic telangiectasia. Arch Dis Child. 2009 Jul; 94(7):506-11.
  13. Kipps A, Alexander M, Colan SD, Gauvreau K, Smoot L, Crawford L, Darras BT, Blume ED. The longitudinal course of cardiomyopathy in Friedreich's ataxia during childhood. Pediatr Cardiol. 2009 Apr; 30(3):306-10.
  14. Obler D, Juraszek AL, Smoot LB, Natowicz MR. Double outlet right ventricle: aetiologies and associations. J Med Genet. 2008 Aug; 45(8):481-97.
  15. Sawasdiwipachai P, Laussen PC, McGowan FX, Smoot L, Casta A. Cardiac arrest after neuromuscular blockade reversal in a heart transplant infant. Anesthesiology. 2007 Oct; 107(4):663-5.
  16. Tubman VN, Smoot L, Heeney MM. Acquired immune cytopenias post-cardiac transplantation respond to rituximab. Pediatr Blood Cancer. 2007 Mar; 48(3):339-44.
  17. Katzman PJ, Smoot LB, Cox GF. Cardiac Registry screening for DiGeorge Critical Region deletion using loss of heterozygosity analysis. Pediatr Dev Pathol. 2006 Jul-Aug; 9(4):266-79.
  18. Lacro RV, Smoot LB. Cardiovascular Disease in Williams-Beuren Syndrome. Williams-Beuren Syndrome (Ed. Morris C,Lenhoff HM,Wang PW). 2006; 107-124.
  19. Smoot L, Crosson J, Thiagarajan R. Device and Alternative Therapies in Pediatric Heart Failure. Treatment of Advanced Heart Disease (Ed. Baughman KL, Baumgartner WA). 2006; 653-662.
  20. Smoot L, Zhang H, Klaiman C, Schultz R, Pober B. . Medical Overview and Genetics of Williams-Beuren Syndrome. Progress in Pediatric Cardiology. 2005; 20:195-205.
  21. Lin AE, Salbert BA, Belmont J, Smoot L. Total is more than the sum of the parts: phenotyping the heart in cardiovascular genetics clinics. Am J Med Genet A. 2004 Dec 1; 131(2):111-4.
  22. Ritinski-Mack L,Obler D, Smoot L, Tsipis J. 22q11 Deletion Syndrome - An Educators Guide to Understanding VCFS. 2004.
  23. Lin AE, Grossfeld PD, Hamilton RM, Smoot L, Gripp KW, Proud V, Weksberg R, Wheeler P, Picker J, Irons M, Zackai E, Marino B, Scott CI, Nicholson L. Further delineation of cardiac abnormalities in Costello syndrome. Am J Med Genet. 2002 Aug 1; 111(2):115-29.
  24. Urbán Z, Riazi S, Seidl TL, Katahira J, Smoot LB, Chitayat D, Boyd CD, Hinek A. Connection between elastin haploinsufficiency and increased cell proliferation in patients with supravalvular aortic stenosis and Williams-Beuren syndrome. Am J Hum Genet. 2002 Jul; 71(1):30-44.
  25. Bacha EB, O'Brian P, Smoot L, DelNido PJ. The Use of Mechanical Support in Pediatric Cardiac Transplantation. Mechanical Support for Cardiac and Respiratory Failure in Pediatric Patients (Ed Duncan B). 2001; 221-232.
  26. Obler D, Boardman K, Smoot L. Cardiovascular Genetics website www.cardiogenetics.org. 2001.
  27. Metcalfe K, Rucka AK, Smoot L, Hofstadler G, Tuzler G, McKeown P, Siu V, Rauch A, Dean J, Dennis N, Ellis I, Reardon W, Cytrynbaum C, Osborne L, Yates JR, Read AP, Donnai D, Tassabehji M. Elastin: mutational spectrum in supravalvular aortic stenosis. Eur J Hum Genet. 2000 Dec; 8(12):955-63.
  28. Smoot LB, Cox GC. . Genetics of Duchenne and Becker Muscular Dystrophies: The Dystrophinopathies. Molecular Genetics of Cardiac Electrophysiology Ed. Berul CI, Towbin JA. 2000; 251-266.
  29. Collins-Nakai,Ruth (Editor) . American College of Cardiology Pediatric and Adult Congenital Cardiac Self-Assessment Program; Pediatric Cardiac Transplant (Section author). 1998.
  30. Smoot LB. Elastin gene deletions in Williams syndrome. Curr Opin Pediatr. 1995 Dec; 7(6):698-701.
  31. Breitbart RE, Liang CS, Smoot LB, Laheru DA, Mahdavi V, Nadal-Ginard B. A fourth human MEF2 transcription factor, hMEF2D, is an early marker of the myogenic lineage. Development. 1993 Aug; 118(4):1095-106.
  32. Yu YT, Breitbart RE, Smoot LB, Lee Y, Mahdavi V, Nadal-Ginard B. Human myocyte-specific enhancer factor 2 comprises a group of tissue-restricted MADS box transcription factors. Genes Dev. 1992 Sep; 6(9):1783-98.
  33. Morell E, Wolfe J, Scheurer M, Thiagarajan R, Morin C, Beke DM, Smoot L, Cheng H, Gauvreau K, Blume ED. Patterns of care at end of life in children with advanced heart disease. Arch Pediatr Adolesc Med. 2012 Aug; 166(8):745-8.
  34. Sol-Church K, Stabley DL, Demmer LA, Agbulos A, Lin AE, Smoot L, Nicholson L, Gripp KW. Male-to-male transmission of Costello syndrome: G12S HRAS germline mutation inherited from a father with somatic mosaicism. Am J Med Genet A. 2009 Mar; 149A(3):315-21.
  35. Moskowitz IP, Wang J, Peterson MA, Pu WT, Mackinnon AC, Oxburgh L, Chu GC, Sarkar M, Berul C, Smoot L, Robertson EJ, Schwartz R, Seidman JG, Seidman CE. Transcription factor genes Smad4 and Gata4 cooperatively regulate cardiac valve development. [corrected] Proc Natl Acad Sci U S A. 2011 Mar 8; 108(10):4006-11.
  36. Rajagopal SK, Ma Q, Obler D, Shen J, Manichaikul A, Tomita-Mitchell A, Boardman K, Briggs C, Garg V, Srivastava D, Goldmuntz E, Broman KW, Benson DW, Smoot LB, Pu WT. Spectrum of heart disease associated with murine and human GATA4 mutation. J Mol Cell Cardiol. 2007 Dec; 43(6):677-85.
  37. Kowalczyk MS, Hughes JR, Babbs C, Sanchez-Pulido L, Szumska D, Sharpe JA, Sloane-Stanley JA, Morriss-Kay GM, Smoot LB, Roberts AE, Watkins H, Bhattacharya S, Gibbons RJ, Ponting CP, Wood WG, Higgs DR. Nprl3 is required for normal development of the cardiovascular system. Mamm Genome. 2012 Aug; 23(7-8):404-15.
  38. Kamisago M, Sharma SD, DePalma SR, Solomon S, Sharma P, McDonough B, Smoot L, Mullen MP, Woolf PK, Wigle ED, Seidman JG, Seidman CE. Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy. N Engl J Med. 2000 Dec 7; 343(23):1688-96.
  39. Gerhard-Herman M, Smoot LB, Wake N, Kieran MW, Kleinman ME, Miller DT, Schwartzman A, Giobbie-Hurder A, Neuberg D, Gordon LB. Mechanisms of premature vascular aging in children with Hutchinson-Gilford progeria syndrome. Hypertension. 2012 Jan; 59(1):92-7.
  40. Saleeb SF, Margossian R, Spencer CT, Alexander ME, Smoot LB, Dorfman AL, Bergersen L, Gauvreau K, Marx GR, Colan SD. Reproducibility of echocardiographic diagnosis of left ventricular noncompaction. J Am Soc Echocardiogr. 2012 Feb; 25(2):194-202.
  41. Singh TP, Faber C, Blume ED, Worley S, Almond CS, Smoot LB, Dillis S, Nasman C, Boyle GJ. Safety and early outcomes using a corticosteroid-avoidance immunosuppression protocol in pediatric heart transplant recipients. J Heart Lung Transplant. 2010 May; 29(5):517-22.
  42. Gordon LB, Kleinman ME, Miller DT, Neuberg DS, Giobbie-Hurder A, Gerhard-Herman M, Smoot LB, Gordon CM, Cleveland R, Snyder BD, Fligor B, Bishop WR, Statkevich P, Regen A, Sonis A, Riley S, Ploski C, Correia A, Quinn N, Ullrich NJ, Nazarian A, Liang MG, Huh SY, Schwartzman A, Kieran MW. Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci U S A. 2012 Oct 9; 109(41):16666-71.
  43. Gordon LB, Kleinman ME, Massaro J, D'Agostino RB, Shappell H, Gerhard-Herman M, Smoot LB, Gordon CM, Cleveland RH, Nazarian A, Snyder BD, Ullrich NJ, Silvera VM, Liang MG, Quinn N, Miller DT, Huh SY, Dowton AA, Littlefield K, Greer MM, Kieran MW. Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome. Circulation. 2016 Jul 12; 134(2):114-25.
  44. Alexander P, Nair A, Smoot L, Wigmore D, McDavitt E, Bastardi H, Fynn-Thompson F, Thiagarajan R. 143: OUTCOMES OF EARLY GRAFT FAILURE IN PEDIATRIC HEART TRANSPLANTATION MANAGED WITH ECMO. Crit Care Med. 2016 Dec; 44(12 Suppl 1):113.
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