Douglas Sawyer
Faculty Member
Last active: 7/21/2014

Profile

We are interested in how the adult heart maintains itself for the 3+ billion heartbeats it must deliver to carry us through life. We use molecular and cellular biological techniques to approach specific questions related to this theme. Our specific ideas and questions are motivated by a clinical interest in understanding the pathophysiology of and treating congestive heart failure.

One specific system under active investigation is the neuregulin/erbB signaling system. The growth factor neuregulin acts through receptor tyrosine kinases in the erbB family to modulate cell growth and survival in many tissues. We have been studying how this works in the heart. Our interest is motivated in part by the clinical observation that treating cancer victims with erbB2-targeted therapies promotes cardiac dysfunction, particularly in patients who have received concurrent anthracyclines. We are using isolated cardiac microvascular endothelial cells and myocytes in primary culture to dissect how this system works. Through a series of small and large animal studies, and most recently a clinical trial, we are part of a team examining whether recombinant neuregulin can be developed as a therapy for heart failure. In parallel, we are applying what we are learning to develop strategies to prevent cardiac injury (and promote repair) in situations such as anthracycline exposure, ischemia, and cardiac amyloidosis.

As part of the NHLBI funded U01 Progenitor Cell Biology Consortium we are working with the Hatzopoulos, Baldwin, and Hong laboratories to identify host factors that regulate myocardial regeneration. We have identified neuregulin as one of those factors that regulates biology of endothelial and myocardial progenitor cells. We are now looking at other factors that may be correctable at the systemic level in a way that optimizes myocardial and other organ function. These are being studied in cell, animal and human tissue studies. We anticipate applying what we learn to develop clinical trials in human heart failure.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Neuregulin-1β induces embryonic stem cell cardiomyogenesis via ErbB3/ErbB2 receptors. Hao J, Galindo CL, Tran TL, Sawyer DB (2014) Biochem J 458(2): 335-41
    › Primary publication · 24364879 (PubMed) · PMC4654571 (PubMed Central)
  2. Impairment of subendocardial perfusion reserve and oxidative metabolism in nonischemic dilated cardiomyopathy. Bell SP, Adkisson DW, Ooi H, Sawyer DB, Lawson MA, Kronenberg MW (2013) J Card Fail 19(12): 802-10
    › Primary publication · 24331202 (PubMed) · PMC3945036 (PubMed Central)
  3. Neuregulin as a heart failure therapy and mediator of reverse remodeling. Galindo CL, Ryzhov S, Sawyer DB (2014) Curr Heart Fail Rep 11(1): 40-9
    › Primary publication · 24234399 (PubMed) · PMC3975684 (PubMed Central)
  4. Relationship between Uric Acid Levels and Diagnostic and Prognostic Outcomes in Acute Heart Failure. Henry-Okafor Q, Collins SP, Jenkins CA, Miller KF, Maron DJ, Naftilan AJ, Weintraub N, Fermann GJ, McPherson J, Menon S, Sawyer DB, Storrow AB (2012) Open Biomark J : 9-15
    › Primary publication · 24058387 (PubMed) · PMC3777695 (PubMed Central)
  5. Type 1 diabetes mellitus abrogates compensatory augmentation of myocardial neuregulin-1β/ErbB in response to myocardial infarction resulting in worsening heart failure. Odiete O, Konik EA, Sawyer DB, Hill MF (2013) Cardiovasc Diabetol : 52
    › Primary publication · 23530877 (PubMed) · PMC3617023 (PubMed Central)
  6. Anthracyclines and heart failure. Sawyer DB (2013) N Engl J Med 368(12): 1154-6
    › Primary publication · 23514294 (PubMed)
  7. ERBB2 inhibition and heart failure. Cote GM, Sawyer DB, Chabner BA (2013) N Engl J Med 368(9): 876
    › Primary publication · 23445109 (PubMed)
  8. Soluble ST2 as a Diagnostic and Prognostic Marker for Acute Heart Failure Syndromes. Henry-Okafor Q, Collins SP, Jenkins CA, Miller KF, Maron DJ, Naftilan AJ, Weintraub N, Fermann GJ, McPherson J, Menon S, Sawyer DB, Storrow AB (2012) Open Biomark J 2012(5): 1-8
    › Primary publication · 23439880 (PubMed) · PMC3578210 (PubMed Central)
  9. Intravenous glial growth factor 2 (GGF2) isoform of neuregulin-1β improves left ventricular function, gene and protein expression in rats after myocardial infarction. Hill MF, Patel AV, Murphy A, Smith HM, Galindo CL, Pentassuglia L, Peng X, Lenneman CG, Odiete O, Friedman DB, Kronenberg MW, Zheng S, Zhao Z, Song Y, Harrell FE, Srinivas M, Ganguly A, Iaci J, Parry TJ, Caggiano AO, Sawyer DB (2013) PLoS One 8(2): e55741
    › Primary publication · 23437060 (PubMed) · PMC3578842 (PubMed Central)
  10. Circulating neuregulin during the transition from stage A to stage B/C heart failure in a breast cancer cohort. Geisberg CA, Abdallah WM, da Silva M, Silverstein C, Smith HM, Abramson V, Mayer I, Means-Powell J, Freehardt D, White B, Lenihan D, Sawyer DB (2013) J Card Fail 19(1): 10-5
    › Primary publication · 23273589 (PubMed) · PMC3562720 (PubMed Central)
  11. ErbB/integrin signaling interactions in regulation of myocardial cell-cell and cell-matrix interactions. Pentassuglia L, Sawyer DB (2013) Biochim Biophys Acta 1833(4): 909-16
    › Primary publication · 23261977 (PubMed)
  12. Heart transplant survival outcomes for adriamycin-dilated cardiomyopathy. Lenneman AJ, Wang L, Wigger M, Frangoul H, Harrell FE, Silverstein C, Sawyer DB, Lenneman CG (2013) Am J Cardiol 111(4): 609-12
    › Primary publication · 23195041 (PubMed) · PMC3563750 (PubMed Central)
  13. Risk stratification in acute heart failure: rationale and design of the STRATIFY and DECIDE studies. Collins SP, Lindsell CJ, Jenkins CA, Harrell FE, Fermann GJ, Miller KF, Roll SN, Sperling MI, Maron DJ, Naftilan AJ, McPherson JA, Weintraub NL, Sawyer DB, Storrow AB (2012) Am Heart J 164(6): 825-34
    › Primary publication · 23194482 (PubMed) · PMC3511776 (PubMed Central)
  14. Galectin 3 complements BNP in risk stratification in acute heart failure. Fermann GJ, Lindsell CJ, Storrow AB, Hart K, Sperling M, Roll S, Weintraub NL, Miller KF, Maron DJ, Naftilan AJ, McPherson JA, Sawyer DB, Christenson R, Collins SP (2012) Biomarkers 17(8): 706-13
    › Primary publication · 22998064 (PubMed) · PMC3678263 (PubMed Central)
  15. 26S proteasome regulation of Ankrd1/CARP in adult rat ventricular myocytes and human microvascular endothelial cells. Samaras SE, Chen B, Koch SR, Sawyer DB, Lim CC, Davidson JM (2012) Biochem Biophys Res Commun 425(4): 830-5
    › Primary publication · 22892129 (PubMed) · PMC3460693 (PubMed Central)
  16. Recent Progress on Chemical Biology of Pluripotent Stem Cell Self-renewal, Reprogramming and Cardiomyogenesis. Hao J, Sawyer DB, Hatzopoulos AK, Hong CC (2011) Recent Pat Regen Med 1(3): 263-274
    › Primary publication · 22787575 (PubMed) · PMC3392203 (PubMed Central)
  17. Disruption of a GATA4/Ankrd1 signaling axis in cardiomyocytes leads to sarcomere disarray: implications for anthracycline cardiomyopathy. Chen B, Zhong L, Roush SF, Pentassuglia L, Peng X, Samaras S, Davidson JM, Sawyer DB, Lim CC (2012) PLoS One 7(4): e35743
    › Primary publication · 22532871 (PubMed) · PMC3332030 (PubMed Central)
  18. Circulating vascular growth factors and central hemodynamic load in the community. Zachariah JP, Xanthakis V, Larson MG, Vita JA, Sullivan LM, Smith HM, Safa R, Peng X, Hamburg N, Levy D, Sawyer DB, Mitchell GF, Vasan RS (2012) Hypertension 59(4): 773-9
    › Primary publication · 22371357 (PubMed) · PMC3336212 (PubMed Central)
  19. ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response. Icli B, Bharti A, Pentassuglia L, Peng X, Sawyer DB (2012) Biochem Biophys Res Commun 418(1): 116-21
    › Primary publication · 22244893 (PubMed) · PMC3273580 (PubMed Central)
  20. Relation of vascular growth factors with CT-derived measures of body fat distribution: the Framingham Heart Study. Kaess BM, Pedley A, Massaro JM, Larson MG, Corsini E, Hoffmann U, Smith HM, Sawyer DB, Vasan RS, Fox CS (2012) J Clin Endocrinol Metab 97(3): 987-94
    › Primary publication · 22170711 (PubMed) · PMC3319207 (PubMed Central)
  21. Geographic variations in heart failure hospitalizations among medicare beneficiaries in the Tennessee catchment area. Ogunniyi MO, Holt JB, Croft JB, Nwaise IA, Okafor HE, Sawyer DB, Giles WH, Mensah GA (2012) Am J Med Sci 343(1): 71-7
    › Primary publication · 21804374 (PubMed) · PMC4074884 (PubMed Central)
  22. Identification of cis- and trans-acting genetic variants explaining up to half the variation in circulating vascular endothelial growth factor levels. Debette S, Visvikis-Siest S, Chen MH, Ndiaye NC, Song C, Destefano A, Safa R, Azimi Nezhad M, Sawyer D, Marteau JB, Xanthakis V, Siest G, Sullivan L, Pfister M, Smith H, Choi SH, Lamont J, Lind L, Yang Q, Fitzgerald P, Ingelsson E, Vasan RS, Seshadri S (2011) Circ Res 109(5): 554-63
    › Primary publication · 21757650 (PubMed) · PMC3193930 (PubMed Central)
  23. The vascular marker soluble fms-like tyrosine kinase 1 is associated with disease severity and adverse outcomes in chronic heart failure. Ky B, French B, Ruparel K, Sweitzer NK, Fang JC, Levy WC, Sawyer DB, Cappola TP (2011) J Am Coll Cardiol 58(4): 386-94
    › Primary publication · 21757116 (PubMed) · PMC3193932 (PubMed Central)
  24. Heart disease in cancer patients: a burgeoning field where optimizing patient care is requiring interdisciplinary collaborations. Lenihan DJ, Sawyer DB (2011) Heart Fail Clin 7(3): xxi-xxiii
    › Primary publication · 21749881 (PubMed)
  25. Neuregulin-1β regulation of embryonic endothelial progenitor cell survival. Safa RN, Peng XY, Pentassuglia L, Lim CC, Lamparter M, Silverstein C, Walker J, Chen B, Geisberg C, Hatzopoulos AK, Sawyer DB (2011) Am J Physiol Heart Circ Physiol 300(4): H1311-9
    › Primary publication · 21239627 (PubMed) · PMC3075022 (PubMed Central)
  26. A genome-wide association study identifies novel loci associated with circulating IGF-I and IGFBP-3. Kaplan RC, Petersen AK, Chen MH, Teumer A, Glazer NL, Döring A, Lam CS, Friedrich N, Newman A, Müller M, Yang Q, Homuth G, Cappola A, Klopp N, Smith H, Ernst F, Psaty BM, Wichmann HE, Sawyer DB, Biffar R, Rotter JI, Gieger C, Sullivan LS, Völzke H, Rice K, Spyroglou A, Kroemer HK, Ida Chen YD, Manolopoulou J, Nauck M, Strickler HD, Goodarzi MO, Reincke M, Pollak MN, Bidlingmaier M, Vasan RS, Wallaschofski H (2011) Hum Mol Genet 20(6): 1241-51
    › Primary publication · 21216879 (PubMed) · PMC3043664 (PubMed Central)
  27. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height. Lanktree MB, Guo Y, Murtaza M, Glessner JT, Bailey SD, Onland-Moret NC, Lettre G, Ongen H, Rajagopalan R, Johnson T, Shen H, Nelson CP, Klopp N, Baumert J, Padmanabhan S, Pankratz N, Pankow JS, Shah S, Taylor K, Barnard J, Peters BJ, Maloney CM, Lobmeyer MT, Stanton A, Zafarmand MH, Romaine SP, Mehta A, van Iperen EP, Gong Y, Price TS, Smith EN, Kim CE, Li YR, Asselbergs FW, Atwood LD, Bailey KM, Bhatt D, Bauer F, Behr ER, Bhangale T, Boer JM, Boehm BO, Bradfield JP, Brown M, Braund PS, Burton PR, Carty C, Chandrupatla HR, Chen W, Connell J, Dalgeorgou C, Boer Ad, Drenos F, Elbers CC, Fang JC, Fox CS, Frackelton EC, Fuchs B, Furlong CE, Gibson Q, Gieger C, Goel A, Grobbee DE, Hastie C, Howard PJ, Huang GH, Johnson WC, Li Q, Kleber ME, Klein BE, Klein R, Kooperberg C, Ky B, Lacroix A, Lanken P, Lathrop M, Li M, Marshall V, Melander O, Mentch FD, Meyer NJ, Monda KL, Montpetit A, Murugesan G, Nakayama K, Nondahl D, Onipinla A, Rafelt S, Newhouse SJ, Otieno FG, Patel SR, Putt ME, Rodriguez S, Safa RN, Sawyer DB, Schreiner PJ, Simpson C, Sivapalaratnam S, Srinivasan SR, Suver C, Swergold G, Sweitzer NK, Thomas KA, Thorand B, Timpson NJ, Tischfield S, Tobin M, Tomaszewski M, Tomaszweski M, Verschuren WM, Wallace C, Winkelmann B, Zhang H, Zheng D, Zhang L, Zmuda JM, Clarke R, Balmforth AJ, Danesh J, Day IN, Schork NJ, de Bakker PI, Delles C, Duggan D, Hingorani AD, Hirschhorn JN, Hofker MH, Humphries SE, Kivimaki M, Lawlor DA, Kottke-Marchant K, Mega JL, Mitchell BD, Morrow DA, Palmen J, Redline S, Shields DC, Shuldiner AR, Sleiman PM, Smith GD, Farrall M, Jamshidi Y, Christiani DC, Casas JP, Hall AS, Doevendans PA, Christie JD, Berenson GS, Murray SS, Illig T, Dorn GW, Cappola TP, Boerwinkle E, Sever P, Rader DJ, Reilly MP, Caulfield M, Talmud PJ, Topol E, Engert JC, Wang K, Dominiczak A, Hamsten A, Curtis SP, Silverstein RL, Lange LA, Sabatine MS, Trip M, Saleheen D, Peden JF, Cruickshanks KJ, März W, O'Connell JR, Klungel OH, Wijmenga C, Maitland-van der Zee AH, Schadt EE, Johnson JA, Jarvik GP, Papanicolaou GJ, Hugh Watkins on behalf of PROCARDIS, Grant SF, Munroe PB, North KE, Samani NJ, Koenig W, Gaunt TR, Anand SS, van der Schouw YT, Meena Kumari on behalf of the Whitehall II Study and the WHII 50K Group, Soranzo N, Fitzgerald GA, Reiner A, Hegele RA, Hakonarson H, Keating BJ (2011) Am J Hum Genet 88(1): 6-18
    › Primary publication · 21194676 (PubMed) · PMC3014369 (PubMed Central)
  28. Race, sex, and age differences in heart failure-related hospitalizations in a southern state: implications for prevention. Husaini BA, Mensah GA, Sawyer D, Cain VA, Samad Z, Hull PC, Levine RS, Sampson UK (2011) Circ Heart Fail 4(2): 161-9
    › Primary publication · 21178017 (PubMed) · PMC3070602 (PubMed Central)
  29. Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology. Eschenhagen T, Force T, Ewer MS, de Keulenaer GW, Suter TM, Anker SD, Avkiran M, de Azambuja E, Balligand JL, Brutsaert DL, Condorelli G, Hansen A, Heymans S, Hill JA, Hirsch E, Hilfiker-Kleiner D, Janssens S, de Jong S, Neubauer G, Pieske B, Ponikowski P, Pirmohamed M, Rauchhaus M, Sawyer D, Sugden PH, Wojta J, Zannad F, Shah AM (2011) Eur J Heart Fail 13(1): 1-10
    › Primary publication · 21169385 (PubMed)
  30. Mechanisms of anthracycline cardiac injury: can we identify strategies for cardioprotection? Sawyer DB, Peng X, Chen B, Pentassuglia L, Lim CC (2010) Prog Cardiovasc Dis 53(2): 105-13
    › Primary publication · 20728697 (PubMed) · PMC2933091 (PubMed Central)
  31. Serum Neuregulin-1beta as a Biomarker of Cardiovascular Fitness. Moondra V, Sarma S, Buxton T, Safa R, Cote G, Storer T, Lebrasseur NK, Sawyer DB (2009) Open Biomark J : 1-5
    › Primary publication · 20634924 (PubMed) · PMC2903891 (PubMed Central)
  32. Circulating insulin-like growth factor-1 and its binding protein-3: metabolic and genetic correlates in the community. Lam CS, Chen MH, Lacey SM, Yang Q, Sullivan LM, Xanthakis V, Safa R, Smith HM, Peng X, Sawyer DB, Vasan RS (2010) Arterioscler Thromb Vasc Biol 30(7): 1479-84
    › Primary publication · 20378848 (PubMed) · PMC2891230 (PubMed Central)
  33. Emerging anticancer therapeutic targets and the cardiovascular system: is there cause for concern? Peng X, Pentassuglia L, Sawyer DB (2010) Circ Res 106(6): 1022-34
    › Primary publication · 20360265 (PubMed) · PMC2872548 (PubMed Central)
  34. Clinical and genetic correlates of circulating angiopoietin-2 and soluble Tie-2 in the community. Lieb W, Zachariah JP, Xanthakis V, Safa R, Chen MH, Sullivan LM, Larson MG, Smith HM, Yang Q, Mitchell GF, Vita JA, Sawyer DB, Vasan RS (2010) Circ Cardiovasc Genet 3(3): 300-6
    › Primary publication · 20348331 (PubMed) · PMC2892960 (PubMed Central)
  35. Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and apoptosis via a non-canonical p38alpha MAPK pathway. Shi J, Guan J, Jiang B, Brenner DA, Del Monte F, Ward JE, Connors LH, Sawyer DB, Semigran MJ, Macgillivray TE, Seldin DC, Falk R, Liao R (2010) Proc Natl Acad Sci U S A 107(9): 4188-93
    › Primary publication · 20150510 (PubMed) · PMC2840082 (PubMed Central)
  36. Is there more for us to learn from oncology?: Examining the implications of anthracycline effects on the young heart. Sawyer DB (2010) Circulation 121(5): 623-5
    › Primary publication · 20100976 (PubMed)
  37. Matrix metalloproteinases and their tissue inhibitors in cardiac amyloidosis: relationship to structural, functional myocardial changes and to light chain amyloid deposition. Biolo A, Ramamurthy S, Connors LH, O'Hara CJ, Meier-Ewert HK, Soo Hoo PT, Sawyer DB, Seldin DC, Seldin DS, Sam F (2008) Circ Heart Fail 1(4): 249-57
    › Primary publication · 19808299 (PubMed) · PMC2774449 (PubMed Central)
  38. Glutathione peroxidase deficiency exacerbates ischemia-reperfusion injury in male but not female myocardium: insights into antioxidant compensatory mechanisms. Lim CC, Bryan NS, Jain M, Garcia-Saura MF, Fernandez BO, Sawyer DB, Handy DE, Loscalzo J, Feelisch M, Liao R (2009) Am J Physiol Heart Circ Physiol 297(6): H2144-53
    › Primary publication · 19801492 (PubMed) · PMC2793140 (PubMed Central)
  39. Neuregulin-1 beta is associated with disease severity and adverse outcomes in chronic heart failure. Ky B, Kimmel SE, Safa RN, Putt ME, Sweitzer NK, Fang JC, Sawyer DB, Cappola TP (2009) Circulation 120(4): 310-7
    › Primary publication · 19597049 (PubMed) · PMC2741393 (PubMed Central)
  40. Inhibition of ErbB2 by receptor tyrosine kinase inhibitors causes myofibrillar structural damage without cell death in adult rat cardiomyocytes. Pentassuglia L, Graf M, Lane H, Kuramochi Y, Cote G, Timolati F, Sawyer DB, Zuppinger C, Suter TM (2009) Exp Cell Res 315(7): 1302-12
    › Primary publication · 19331811 (PubMed) · PMC4991362 (PubMed Central)
  41. Vascular endothelial growth factor, its soluble receptor, and hepatocyte growth factor: clinical and genetic correlates and association with vascular function. Lieb W, Safa R, Benjamin EJ, Xanthakis V, Yin X, Sullivan LM, Larson MG, Smith HM, Vita JA, Mitchell GF, Sawyer DB, Vasan RS (2009) Eur Heart J 30(9): 1121-7
    › Primary publication · 19223316 (PubMed) · PMC2721714 (PubMed Central)
  42. Palmitate alters neuregulin signaling and biology in cardiac myocytes. Miller TA, Icli B, Cote GM, Lebrasseur NK, Borkan SC, Pimentel DR, Peng X, Sawyer DB (2009) Biochem Biophys Res Commun 379(1): 32-7
    › Primary publication · 19070592 (PubMed) · PMC2654183 (PubMed Central)
  43. The role of Neuregulin-1beta/ErbB signaling in the heart. Pentassuglia L, Sawyer DB (2009) Exp Cell Res 315(4): 627-37
    › Primary publication · 18801360 (PubMed) · PMC2667947 (PubMed Central)
  44. Anthracycline cardiotoxicity: from bench to bedside. Gianni L, Herman EH, Lipshultz SE, Minotti G, Sarvazyan N, Sawyer DB (2008) J Clin Oncol 26(22): 3777-84
    › Primary publication · 18669466 (PubMed) · PMC3018290 (PubMed Central)
  45. Predicting and preventing the cardiotoxicity of cancer therapy. Anderson B, Sawyer DB (2008) Expert Rev Cardiovasc Ther 6(7): 1023-33
    › Primary publication · 18666852 (PubMed)
  46. Molecular and cellular mechanisms of anthracycline cardiotoxicity. Chen B, Peng X, Pentassuglia L, Lim CC, Sawyer DB (2007) Cardiovasc Toxicol 7(2): 114-21
    › Primary publication · 17652815 (PubMed)
  47. Clinical and echocardiographic correlates of plasma procollagen type III amino-terminal peptide levels in the community. Wang TJ, Larson MG, Benjamin EJ, Siwik DA, Safa R, Guo CY, Corey D, Sundstrom J, Sawyer DB, Colucci WS, Vasan RS (2007) Am Heart J 154(2): 291-7
    › Primary publication · 17643579 (PubMed) · PMC3170820 (PubMed Central)
  48. Simultaneous orientation and cellular force measurements in adult cardiac myocytes using three-dimensional polymeric microstructures. Zhao Y, Lim CC, Sawyer DB, Liao R, Zhang X (2007) Cell Motil Cytoskeleton 64(9): 718-25
    › Primary publication · 17615571 (PubMed)
  49. Cardiac amyloidosis: shifting our impressions to hopeful. Sawyer DB, Skinner M (2006) Curr Heart Fail Rep 3(2): 64-71
    › Primary publication · 16928339 (PubMed)