Lawreen Heller Connors, PhD

Associate Professor, Pathology & Laboratory Medicine

Lawreen Connors
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 7/21/2018

    Giadone RM, Rosarda JD, Akepati PR, Thomas AC, Boldbaatar B, James MF, Wilson AA, Sanchorawala V, Connors LH, Berk JL, Wiseman RL, Murphy GJ. A library of ATTR amyloidosis patient-specific induced pluripotent stem cells for disease modelling and in vitro testing of novel therapeutics. Amyloid. 2018 Jul 21; 1-8. PMID: 30032658.

    Read at: PubMed
  • Published on 6/25/2018

    Klimtchuk ES, Prokaeva T, Frame NM, Abdullahi HA, Spencer B, Dasari S, Cui H, Berk JL, Kurtin PJ, Connors LH, Gursky O. Unusual duplication mutation in a surface loop of human transthyretin leads to an aggressive drug-resistant amyloid disease. Proc Natl Acad Sci U S A. 2018 Jul 10; 115(28):E6428-E6436. PMID: 29941560.

    Read at: PubMed
  • Published on 6/19/2018

    Mints YY, Doros G, Berk JL, Connors LH, Ruberg FL. Features of atrial fibrillation in wild-type transthyretin cardiac amyloidosis: a systematic review and clinical experience. ESC Heart Fail. 2018 Jun 19. PMID: 29916559.

    Read at: PubMed
  • Published on 2/9/2018

    Phull P, Sanchorawala V, Connors LH, Doros G, Ruberg FL, Berk JL, Sarosiek S. Monoclonal gammopathy of undetermined significance in systemic transthyretin amyloidosis (ATTR). Amyloid. 2018 Mar; 25(1):62-67. PMID: 29424556.

    Read at: PubMed
  • Published on 2/1/2018

    Hanson JLS, Arvanitis M, Koch CM, Berk JL, Ruberg FL, Prokaeva T, Connors LH. Use of Serum Transthyretin as a Prognostic Indicator and Predictor of Outcome in Cardiac Amyloid Disease Associated With Wild-Type Transthyretin. Circ Heart Fail. 2018 Feb; 11(2):e004000. PMID: 29449366.

    Read at: PubMed
  • 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 7/29/2017

    Prokaeva T, Akar H, Spencer B, Havasi A, Cui H, O'Hara CJ, Gursky O, Leszyk J, Steffen M, Browning S, Rosenberg A, Connors LH. Hereditary Renal Amyloidosis Associated With a Novel Apolipoprotein A-II Variant. Kidney Int Rep. 2017 Nov; 2(6):1223-1232. PMID: 29270531.

    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

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