{"id":1819,"date":"2012-04-11T10:57:52","date_gmt":"2012-04-11T14:57:52","guid":{"rendered":"https:\/\/www.bu.edu\/amyloid\/?page_id=1819"},"modified":"2018-12-04T15:22:43","modified_gmt":"2018-12-04T20:22:43","slug":"lawreen-h-connors-ph-d","status":"publish","type":"page","link":"https:\/\/www.bu.edu\/amyloid\/lawreen-h-connors-ph-d\/","title":{"rendered":"Lawreen H. Connors, Ph.D."},"content":{"rendered":"<h3>Professor of Pathology and Biochemistry<\/h3>\n<p><strong>Director<\/strong>, <span>Alan and Sandra Gerry Amyloid Research Laboratory<\/span>,\u00a0Amyloidosis Center<\/p>\n<h3><img loading=\"lazy\" width=\"355\" height=\"301\" class=\"wp-image-3256 alignright\" alt=\"LC Picture\" src=\"\/amyloid\/files\/2017\/10\/LC-Picture-e1507838800927-650x550.jpg\" srcset=\"https:\/\/www.bu.edu\/amyloid\/files\/2017\/10\/LC-Picture-e1507838800927-650x550.jpg 650w, https:\/\/www.bu.edu\/amyloid\/files\/2017\/10\/LC-Picture-e1507838800927-768x650.jpg 768w, https:\/\/www.bu.edu\/amyloid\/files\/2017\/10\/LC-Picture-e1507838800927-1024x867.jpg 1024w\" sizes=\"(max-width: 355px) 100vw, 355px\" \/><\/h3>\n<p><strong>Co-director<\/strong>, Amyloid Pathology and Molecular Testing Laboratory, Boston Medical Center<\/p>\n<p><strong>Affiliations:<\/strong><\/p>\n<ul>\n<li>Department of Pathology and Laboratory Medicine, Boston University School of Medicine (BUSM)<\/li>\n<li>Biochemistry, BUSM<\/li>\n<\/ul>\n<p><strong>Education:<\/strong><\/p>\n<ul>\n<li>Boston College, B.S. (Chemistry, Mathematics)<\/li>\n<li>Tufts University, M.S. (Chemistry)<\/li>\n<li>Boston University, Ph.D. (Biochemistry)<\/li>\n<\/ul>\n<p><strong>Board Membership: <\/strong><em>Amyloid<\/em> Journal Editorial Board member<\/p>\n<p><strong>Professional Societies:<\/strong> International Society for Amyloidosis<\/p>\n<p><strong>Research Interests:<\/strong><\/p>\n<ul>\n<li>Principal Investigator:\u00a0 Molecular mechanism of senile cardiac amyloidosis (NIH \/ R01-AG031804)<\/li>\n<li>Principal Investigator:\u00a0 Blood Profiling for Biomarkers in Age-related \u2018Senile\u2019 Systemic Amyloidosis, SSA (E. Rhodes and Leona B. Carpenter Foundation\u00a0Grant)<\/li>\n<li>\u00a0Co-Investigator: Novel insights of pathogenesis of light chain cardiac amyloidosis (NIH \/ R21-HL095891-01A1)<\/li>\n<li>Co-Investigator: Studies of murine antibody 2A4 and AL LC amyloid tissues\/purified proteins (Neotope Biosciences Sponsored Research Grant)<\/li>\n<li>Consultant: Oxidative stress, matrix remodeling, and stem cell transplant in cardiac amyloidosis (AHA NCRP, NSDG)<\/li>\n<\/ul>\n<p>The systemic amyloid diseases are protein misfolding and deposition disorders.\u00a0 These pathologies feature the destabilization of one of several plasma proteins; the amyloidogenic protein adopts a non-native conformation that leads to aberrant self-association and aggregation.\u00a0 The aggregates form defined fibrillar structures which ultimately precipitate as amyloid deposits in the extracellular compartments of targeted tissues\/organs.\u00a0 In addition to the mechanical disruption of tissue function by the deposited amyloid fibrils, pathological effects are thought to be related to the acute cellular toxicity of soluble prefibrillar amyloid aggregates.<\/p>\n<p>We are studying the amyloidogenic nature of transthyretin (TTR), normally a soluble protein present in plasma and cerebral spinal fluid.\u00a0 Both wild-type and variant forms of TTR can form amyloid deposits, but disease onset is delayed in what appears to be an age-dependent mechanism.\u00a0 Our investigations are aimed at identifying specific factors required to initiate the disease process; these factors likely include structural features that are both intrinsic and extrinsic to TTR.\u00a0 Specific areas of interest include the roles of amino acid alterations, post-translational modifications (glycosylation, sulfonation, cysteinylation) and heteroassociations in TTR amyloid fibril formation.<\/p>\n<p>We have extensively characterized TTR proteins derived from clinical specimens and identified proteomic differences in patient vs. age-matched control serum and tissue samples.\u00a0 TTR structural modifications and heteroassociations identified in the clinical samples are studied in vitro with recombinantly-generated proteins and several compounds, including diflunisal and \u03b1-tocopherol, are being investigated as potential inhibitors of TTR aggregation and fibril formation.\u00a0 Furthermore, since TTR-associated amyloid diseases often feature cardiomyopathy, we are also studying the effects of amyloidogenic forms of TTR on cultured primary cardiac cells.<\/p>\n<p><strong>Selected Recent Publications<\/strong><strong>:<\/strong><\/p>\n<ul>\n<li>Chan GG, Koch CM, and <strong>Connors LH<\/strong>:\u00a0 Serum proteomic variability associated with clinical phenotype in familial transthyretin amyloidosis (ATTRm).\u00a0 <em>J Proteome Res<\/em>, 2017.\u00a0 [Epub ahead of print]<\/li>\n<li>Prokaeva T, Akar H, Spencer B, Havasi A, Cui H, O\u2019Hara CJ, Gursky O, Leszyk J, Steffen M, Browning S, Rosenberg A, and <strong>Connors LH<\/strong>: Hereditary renal amyloidosis associated with a novel apolipoprotein A-II variant: a possible link between clinical phenotype and protein structure. Kidney Int Rep, 2017, In Press.<\/li>\n<li>Klimtchuk ES, Prokaeva TB, Spencer BH, Gursky O, and <strong>Connors LH<\/strong>: In vitro co-expression of human amyloidogenic immunoglobulin light and heavy chain proteins: a relevant cell-based model of AL amyloidosis. Amyloid:Journal of Protein Folding Disorders, 24 (2):115-22, 2017.<\/li>\n<li>Chan GG, Koch CM, and <strong>Connors LH<\/strong>: Blood proteomic profiling in inherited (ATTRm) and acquired (ATTRwt) forms of transthyretin-associated cardiac amyloidosis. J Proteome Res, 16(4):1659-1668, 2017.<\/li>\n<li><strong>Connors LH<\/strong>, Sam F, Skinner M, Salinaro F, Sun F, Ruberg FL, Berk JL, Seldin DC: \u00a0Heart Failure Resulting From Age-Related Cardiac Amyloid Disease Associated With Wild-Type Transthyretin: A Prospective, Observational Cohort Study. \u00a0<em>Circulation,<\/em>\u00a0133(3):282-90, 2016.<\/li>\n<li>Sikora JL, Logue MW, Chan GG, Spencer BH, Prokaeva TB, Baldwin CT, Seldin DC, and <b>Connors LH<\/b>:\u00a0 Genetic variation of the transthyretin gene in wild-type transthyretin amyloidosis (ATTRwt).\u00a0 <i>Hum Genet<\/i>, 134 (1):111-121, 2015.<\/li>\n<li>Greene MJ, Klimtchuk ES, Seldin DC, Berk JL, and <b>Connors LH<\/b>: \u00a0Cooperative stabilization of transthyretin by clusterin and diflunisal.\u00a0\u00a0<em>Biochemistry,<\/em> 54(2):268-78, 2015.<\/li>\n<li>Sarosiek S, Seldin DC, <strong>Connors LH<\/strong>, Spencer B, Murakami A, O&#8217;Hara C, and Sanchorawala V: \u00a0Vertebral compression fractures as the initial presentation of AL amyloidosis: case series and review of literature. \u00a0<em>Amyloid<\/em>, 22(3):156-62, 2015.<\/li>\n<li>Phay M, Blinder V, Macy S, Greene MJ, Wooliver DC, Liu W, Planas A, Walsh DM, <b>Connors LH<\/b>, Primmer SR, Planque SA, Paul S, and O&#8217;Nuallain B:\u00a0 Transthyretin aggregate-specific antibodies recognize cryptic epitopes on patient-derived amyloid fibrils.\u00a0 <i>Rejuvenation Res,<\/i> 17(2):97-104, 2014.<\/li>\n<li>Guan J, Mishra S, Qiu Y, Shi J, Trudeau K, Las G, Liesa M, Shirihai O, <b>Connors LH<\/b>, Seldin DC, Falk RH, MacRae CA, and Liao R:\u00a0 Impaired autophagy and lysosomal dysfunction underlie the pathogenesis of amyloidogenic light chain mediated cardiotoxicity.\u00a0 <i>EMBO Mol Med<\/i>, 6(11):1493-507, 2014.<\/li>\n<li>Reddi HV, Jenkins S, Theis J, Thomas BC, <b>Connors LH<\/b>, Van Rhee F, and Highsmith WE Jr:\u00a0 Homozygosity for the V122I mutation in transthyretin is associated with earlier onset of cardiac amyloidosis in the African American population in the seventh decade of life.\u00a0 <i>J Mol Diagnostics,<b> <\/b><\/i>16(1):68-74, 2014.<\/li>\n<li>Leung A, Nah SK, Reid W, Ebata A, Koch CM, Monti S, Genereux JC, Wiseman RL, Wolozin B, <b>Connors LH<\/b>, Berk JL, Seldin DC, Mostoslavsky G, Kotton DN, and Murphy GJ:\u00a0 Induced pluripotent stem cell modeling of multisystemic, hereditary transthyretin amyloidosis.\u00a0 <i>Stem Cell Reports<\/i>, 1(5):451-63, 2013.<\/li>\n<li>Tanaka K, Essick EE, Doros G, Tanriverdi K, <b>Connors LH<\/b>, Seldin DC, and Sam F:\u00a0 Circulating matrix metalloproteinases and tissue inhibitors of metalloproteinases in cardiac amyloidosis.\u00a0 <i>J Am Heart Assoc<\/i>, Mar 12;2(2):e005868, 2013.<\/li>\n<li>Guan J, Mishra S, Shi J, Plovie E, Qiu Y, Cao X, Gianni D, Jiang B, Del Monte F, <b>Connors LH<\/b>, Seldin DC, Lavatelli F, Rognoni P, Palladini G, Merlini G, Falk RH, Semigran MJ, Dec GW Jr, MacRae CA, and Liao R:\u00a0 Stanniocalcin1 is a key mediator of amyloidogenic light chain induced cardiotoxicity.\u00a0 <i>Basic Res Cardiol<\/i>, 108(5): 378, 2013.<\/li>\n<li>Mishra S, Guan J, Plovie E, Seldin DC, <b>Connors LH<\/b>, Merlini G, MacRae CA, and Liao R:\u00a0 Human amyloidogenic light chain proteins result in cardiac dysfunction, cell death and early mortality in zebrafish.\u00a0 Am J Physiol Heart Circ Physiol, 305(1):H95-H103, 2013.<\/li>\n<li>Kingsbury JS, Laue TM, Chase SF, and <strong>Connors LH<\/strong>:\u00a0 Detection of high molecular weight amyloid serum protein complexes using Biological On-Line Tracer Sedimentation (BOLTS).\u00a0 <em>Anal Biochem<\/em>, Accepted for Publication, 2012.<\/li>\n<li><strong>Connors LH<\/strong>, Doros G, Sam F, Badiee A, Seldin DC, and Skinner M:\u00a0 Clinical features and survival in senile systemic amyloidosis: comparison to familial transthyretin cardiomyopathy.\u00a0 <em>Amyloid:Journal of Protein Folding Disorders<\/em>, 18 (Suppl 1):157-9, 2011.<\/li>\n<li>Greene MJ, Sam F, Soohoo P, Patel R, Seldin DC, and <strong>Connors LH<\/strong>:\u00a0 Evidence for a functional role of the molecular chaperone clusterin in amyloidotic cardiomyopathy. <em>\u00a0J Am Path<\/em>, 178(1):61-8, 2011.<\/li>\n<li>Hovey BM, Ward JE, Soo Hoo, O\u2019Hara C, <strong>Connors LH<\/strong>, and Seldin DC:\u00a0 Preclinical development of siRNA therapeutics for AL amyloidosis. <em>Gene Therapy<\/em>, 18(12):1150-6, 2011.<\/li>\n<li>Ward JE, SooHoo P, O\u2019Hara C, Toraldo G, Jasuja R, Guan J, Liao R, <strong>Connors LH<\/strong>, and Seldin DC:\u00a0 A transgenic mouse model of AL amyloidosis and its use in testing oral therapeutics.\u00a0 <em>Blood<\/em>, 118(25):6610-7, 2011.<\/li>\n<li>Weng L, Spencer B, Soo Hoo P, <strong>Connors LH<\/strong>, O\u2019Hara C, and Seldin DC:\u00a0 Dysregulation of miRNAs in AL amyloidosis.\u00a0 <em>Amyloid:Journal of Protein Folding Disorders<\/em>, 18(3):128-35, 2011.<\/li>\n<\/ul>\n<p><strong>Search Additional Publications<\/strong>: <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/sites\/myncbi\/lawreen.connors.1\/bibliography\/40342575\/public\/?sort=date&amp;direction=descending\">http:\/\/www.ncbi.nlm.nih.gov\/sites\/myncbi\/lawreen.connors.1\/bibliography\/40342575\/public\/?sort=date&amp;direction=descending<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Professor of Pathology and Biochemistry Director, Alan and Sandra Gerry Amyloid Research Laboratory,\u00a0Amyloidosis Center Co-director, Amyloid Pathology and Molecular Testing Laboratory, Boston Medical Center Affiliations: Department of Pathology and Laboratory Medicine, Boston University School of Medicine (BUSM) Biochemistry, BUSM Education: Boston College, B.S. (Chemistry, Mathematics) Tufts University, M.S. (Chemistry) Boston University, Ph.D. (Biochemistry) Board Membership: [&hellip;]<\/p>\n","protected":false},"author":5531,"featured_media":0,"parent":0,"menu_order":14,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/www.bu.edu\/amyloid\/wp-json\/wp\/v2\/pages\/1819"}],"collection":[{"href":"https:\/\/www.bu.edu\/amyloid\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.bu.edu\/amyloid\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.bu.edu\/amyloid\/wp-json\/wp\/v2\/users\/5531"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bu.edu\/amyloid\/wp-json\/wp\/v2\/comments?post=1819"}],"version-history":[{"count":40,"href":"https:\/\/www.bu.edu\/amyloid\/wp-json\/wp\/v2\/pages\/1819\/revisions"}],"predecessor-version":[{"id":3680,"href":"https:\/\/www.bu.edu\/amyloid\/wp-json\/wp\/v2\/pages\/1819\/revisions\/3680"}],"wp:attachment":[{"href":"https:\/\/www.bu.edu\/amyloid\/wp-json\/wp\/v2\/media?parent=1819"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}