Lawreen H. Connors

Associate Research ProfessorLawreen Connors

Boston University School of Medicine
Silvio Conte Building, Office: K507; Lab: K508
72 E. Concord Street
Boston, MA 02118

Phone: 617-638-4313
Lab Phone: 617-638-4348
Fax: 617-638-5226

Email: lconnors@bu.edu

Education:

B.S., Chemistry, Mathematics, Boston College, Chestnut Hill, MA
M.S., Chemistry, Tufts University, Medford, MA
Ph.D., Biochemistry, Boston University, Boston, MA

Research Interest:

The systemic amyloid diseases are protein misfolding and deposition disorders.  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.  The aggregates form defined fibrillar structures which ultimately precipitate as amyloid deposits in the extracellular compartments of targeted tissues/organs.  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.  We are studying the amyloidogenic nature of transthyretin (TTR), normally a soluble protein present in plasma and cerebral spinal fluid.  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.  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.  Specific areas of interest include the roles of amino acid alterations, post-translational modifications (glycosylation, sulfonation, cysteinylation) and heteroassociations in TTR amyloid fibril formation.  We have extensively characterized TTR proteins derived from clinical specimens and identified proteomic differences in patient vs. age-matched control serum and tissue samples.  TTR structural modifications and heteroassociations identified in the clinical samples are studied in vitro with recombinantly-generated proteins and several compounds, including diflunisal and α-tocopherol, are being investigated as potential inhibitors of TTR aggregation and fibril formation.  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.

Representative Publications:

PubMed