Lawreen Heller Connors, PhD

Associate Professor, Pathology & Laboratory Medicine

(617) 638-4313
72 E. Concord St Silvio Conte (K)

Biography

My research focuses on understanding the amyloidogenic nature of transthyretin (TTR), normally a soluble protein present in plasma and cerebral spinal fluid. Both wild-type and specific variant forms of TTR can be amyloidogenic, but disease onset is delayed in what appears to be an age-dependent mechanism. Our investigations are aimed at identifying specific age-related factors required to initiate the disease process; these factors likely include structural features that are both intrinsic and extrinsic to TTR. My research attempts to link protein biochemistry to disease pathology by studying the role of amino acid alterations, post-translational modifications (glycosylation, sulfonation, cysteinylation and phosphorylation) and metabolic processing in TTR amyloid fibril formation. We have precisely defined the molecular composition of numerous amyloidogenic TTR proteins derived from patient serum and tissue samples using mass spectrometry, analytical ultracentrifugation, and electron microscopy. In addition, using a proteomic approach, we have identified several tissue components present in patient specimens which may be effectors of amyloidogenesis. With recombinantly-generated proteins, we are studying the molecular stability of various forms of TTR, as well as the heteroassociations of TTR with these deposited molecular constituents using electrophoretic, chromatographic, and histological techniques. A translational component of our studies involves the study of a variety of compounds, including the small molecules diflunisal and a-tocopherol, as potential inhibitors of TTR aggregation and fibril formation. Furthermore, since TTR-associated amyloid diseases often feature cardiomyopathies, we are also studying the direct and indirect effects of amyloidogenic forms of TTR on cultured primary cardiac cells.

Other Positions

  • Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences
  • Associate Professor, Biochemistry, Boston University School of Medicine

Education

  • Boston University, PhD
  • Tufts University, MS
  • Boston College, BS

Publications

  • Published on 10/20/2017

    Arvanitis M, Chan GG, Jacobson DR, Berk JL, Connors LH, Ruberg FL. Prevalence of mutant ATTR cardiac amyloidosis in elderly African Americans with heart failure. Amyloid. 2017 Dec; 24(4):253-255. PMID: 29052438.

    Read at: PubMed
  • Published on 9/27/2017

    Chan GG, Koch CM, Connors LH. Serum Proteomic Variability Associated with Clinical Phenotype in Familial Transthyretin Amyloidosis (ATTRm). J Proteome Res. 2017 Nov 03; 16(11):4104-4112. PMID: 28922609.

    Read at: PubMed
  • Published on 6/20/2017

    Klimtchuk ES, Prokaeva TB, Spencer BH, Gursky O, Connors LH. In vitro co-expression of human amyloidogenic immunoglobulin light and heavy chain proteins: a relevant cell-based model of AL amyloidosis. Amyloid. 2017 Jun; 24(2):115-122. PMID: 28632419.

    Read at: PubMed
  • Published on 3/1/2017

    Benson MD, Berk JL, Connors LH, Dasgupta NR. Familial wild-type transthyretin cardiomyopathy. Amyloid. 2017 Mar; 24(sup1):91-92. PMID: 28434303.

    Read at: PubMed
  • Published on 3/1/2017

    Arvanitis M, Simon S, Chan G, Fine D, Beardsley P, LaValley M, Jacobson D, Koch C, Berk JL, Connors LH, Ruberg FL. Retinol binding protein 4 (RBP4) concentration identifies V122I transthyretin cardiac amyloidosis. Amyloid. 2017 Mar; 24(sup1):120-121. PMID: 28434357.

    Read at: PubMed
  • Published on 3/1/2017

    Arvanitis M, Koch CM, Chan GG, Torres-Arancivia C, LaValley MP, Jacobson DR, Berk JL, Connors LH, Ruberg FL. Identification of Transthyretin Cardiac Amyloidosis Using Serum Retinol-Binding Protein 4 and a Clinical Prediction Model. JAMA Cardiol. 2017 Mar 01; 2(3):305-313. PMID: 28196196.

    Read at: PubMed
  • Published on 2/23/2017

    Chan GG, Koch CM, Connors LH. Blood Proteomic Profiling in Inherited (ATTRm) and Acquired (ATTRwt) Forms of Transthyretin-Associated Cardiac Amyloidosis. J Proteome Res. 2017 Apr 07; 16(4):1659-1668. PMID: 28196416.

    Read at: PubMed
  • Published on 9/28/2016

    Prokaeva T, Spencer B, Sun F, O'Hara RM, Seldin DC, Connors LH, Sanchorawala V. Immunoglobulin heavy light chain test quantifies clonal disease in patients with AL amyloidosis and normal serum free light chain ratio. Amyloid. 2016 Dec; 23(4):214-220. PMID: 27677679.

    Read at: PubMed
  • Published on 12/11/2015

    Connors LH, Sam F, Skinner M, Salinaro F, Sun F, Ruberg FL, Berk JL, Seldin DC. Heart Failure Resulting From Age-Related Cardiac Amyloid Disease Associated With Wild-Type Transthyretin: A Prospective, Observational Cohort Study. Circulation. 2016 Jan 19; 133(3):282-90. PMID: 26660282.

    Read at: PubMed
  • Published on 6/25/2015

    Sarosiek S, Seldin DC, Connors LH, Spencer B, Murakami A, O'Hara C, Sanchorawala V. Vertebral compression fractures as the initial presentation of AL amyloidosis: case series and review of literature. Amyloid. 2015; 22(3):156-62. PMID: 26104853.

    Read at: PubMed

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