Lawreen Heller Connors, PhD
Professor
Boston University School of Medicine
Dept of Pathology & Laboratory Medicine

PhD, Boston University
MS, Tufts University



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.

Associate Professor
Boston University School of Medicine
Biochemistry


Graduate Faculty (Primary Mentor of Grad Students)
Boston University School of Medicine, Graduate Medical Sciences




MOLECULAR MECHANISM OF SENILE CARDIAC AMYLOIDOSIS
09/15/2017 - 08/31/2019 (PI)
NIH/National Institute on Aging
2R56AG031804-06A1

VALIDATION OF BLOOD BIOMARKERS FOR RECOGNITION AND MONITORING OF AGE-RELATED, WILD-TYPE TRANSTHYRETIN AMYLOIDOSIS (ATTRWT)
01/01/2018 - 12/31/2018 (PI)
E. Rhodes & Leona B. Carpenter Foundation

CONTRIBUTION OF IMMUNOGLOBULIN CONSTANT DOMAIN TO AMYLOID FORMATION, PART 4
01/01/2011 - 12/31/2018 (PI)
Florida Wildflower Foundation

IMMUNOHISTOCHEMICAL ANALYSES OF PROCLARA FUSION PROTEIN, NPT189, IN AMYLOID-INFILTRATED HUMAN HEART TISSUES
01/02/2018 - 06/30/2018 (PI)
Proclara Biosciences

CONGO RED HISTOLOGIC ANALYSIS FOR MOUSE TISSUE - DICERNA PHARMACEUTICALS, INC.
02/22/2017 - 03/31/2017 (PI)
Dicerna Pharmaceuticals, Inc.

SERUM BIOMARKER IDENTIFICATION OF CARDIAC AMYLOIDOSIS IN ELDERLY AFRICAN AMERICANS
04/01/2016 - 03/31/2017 (PI)
Boston Medical Center Corporation NIH NIA
5R21AG050206-02

DISCOVERY: A STUDY EXAMINING THE PREVALENCE OF TTR MUTATIONS IN SUBJECTS
09/01/2015 - 08/31/2016 (PI)
Alnylam Pharmaceuticals, Inc.

BLOOD PROFILING FOR BIOMARKERS IN AGE-RELATED SENILE SYSTEMIC AMYLOIDOSIS (SSA)
07/01/2014 - 06/30/2016 (PI)
E. Rhodes & Leona B. Carpenter Foundation

MOLECULAR MECHANISM OF SENILE CARDIAC AMYLOIDOSIS
09/01/2009 - 08/31/2015 (PI)
NIH/National Institute on Aging
5R01AG031804-05

MOLECULAR MECHANISM OF SENILE CARDIAC AMYLOIDOSIS
09/01/2009 - 08/31/2014 (PI)
NIH/National Institute on Aging
5R01AG031804-03

Showing 10 of 15 results. Show All Results



Yr Title Project-Sub Proj Pubs
2017 Molecular mechanism of senile cardiac amyloidosis 2R56AG031804-06A1
2013 Molecular mechanism of senile cardiac amyloidosis 5R01AG031804-05 9
2012 Molecular mechanism of senile cardiac amyloidosis 5R01AG031804-04 9
2011 S-SULFONATION OF SERUM TRANSTHYRETIN IN SSA/PTMS OF TTR IN AMYLOID FIBRILS 5P41RR010888-15-5084 236
2011 Molecular mechanism of senile cardiac amyloidosis 5R01AG031804-03 9
2010 S-SULFONATION OF SERUM TRANSTHYRETIN IN SSA/PTMS OF TTR IN AMYLOID FIBRILS 5P41RR010888-14-6781 236
2010 Molecular mechanism of senile cardiac amyloidosis 5R01AG031804-02 9
2009 Molecular mechanism of senile cardiac amyloidosis 1R01AG031804-01A2 9
2009 S-SULFONATION OF SERUM TRANSTHYRETIN IN SSA/PTMS OF TTR IN AMYLOID FIBRILS 5P41RR010888-13-6127 236
2009 ULTRACENTRIFUGATION OF AMYLOID PROTEIN COMPLEXES WITH FLUORESCENCE DETECTION 5P41RR010888-13-6199 236
Showing 10 of 17 results. Show All Results
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

  1. 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 Sep; 25(3):148-155.View Related Profiles. PMID: 30032658.
     
  2. 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 07 10; 115(28):E6428-E6436.View Related Profiles. PMID: 29941560.
     
  3. 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 10; 5(5):772-779.View Related Profiles. PMID: 29916559.
     
  4. 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.View Related Profiles. PMID: 29424556.
     
  5. 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.View Related Profiles. PMID: 29449366.
     
  6. 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 12; 24(4):253-255.View Related Profiles. PMID: 29052438.
     
  7. 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.View Related Profiles. PMID: 28922609.
     
  8. 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.View Related Profiles. PMID: 29270531.
     
  9. 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.View Related Profiles. PMID: 28632419.
     
  10. Benson MD, Berk JL, Connors LH, Dasgupta NR. Familial wild-type transthyretin cardiomyopathy. Amyloid. 2017 Mar; 24(sup1):91-92.View Related Profiles. PMID: 28434303.
     
Showing 10 of 83 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 83 publications over 26 distinct years, with a maximum of 8 publications in 2017

YearPublications
19831
19841
19854
19861
19871
19981
19994
20003
20013
20022
20032
20042
20054
20061
20076
20084
20094
20104
20116
20122
20135
20144
20153
20162
20178
20185
In addition to these self-described keywords below, a list of MeSH based concepts is available here.

amyloidosis
cardiomyopathy
diflunisal
transthyretin
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72 E. Concord St Silvio Conte (K)
Boston MA 02118
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