Accomplishments

Contributions to Laboratory Research:
Definition of the electron microscopic structure and x-ray diffraction pattern of amyloid fibrils in 1967, providing key insight and first guiding principles in understanding the unique characteristics of insoluble amyloid proteins.
Development of a procedure for isolating and purifying amyloid proteins from tissues, making possible biochemical analyses and precise identification of the proteins.
Creation of an animal model of secondary amyloidosis using casein injections, permitting testing of AA amyloid formation and treatment in a controlled laboratory environment.
Identification of the protein deposits in familial amyloidosis as transthyretin, which for the first time defined the biochemical nature and source of the amyloid fibril in this form of amyloidosis.
Characterization of the protein deposits in dialysis-associated amyloidosis as ß2-microglobulin, a protein not properly cleared from the circulation by dialysis membranes.
Development of a simple electrophoretic method to differentiate primary and hereditary amyloidosis, through an isoelectric focusing technique to identify transthyretin mutant protein in serum.
Construction of ALBase, a public database of containing >3000 deidentified light chain nucleotide and amino acid sequences available to researchers worldwide.
Development of mouse models of AL amyloidosis for studying the process of AL amyloidogenesis.
Development of siRNA approaches for reducing AL light chain production, and collaborating with Alnylam Co. on siRNA for ATTR.
Development of novel methodologies for analysis of transthyretin (TTR) aggregates in serum and tissues for better understanding of familial and age-related transthyretin amyloidosis.

 

Contributions to Clinical Research:
Description of the natural history of amyloid diseases, which varies with each clinical type with respect to organ system involvement, progression, prognosis, and treatment options.
Development of a simple biopsy test, the abdominal fat aspirate, for the diagnosis of systemic amyloidosis, offering a less-invasive, highly sensitive alternative to the standard organ biopsy.
Characterization of cardiac and other organ system involvements in amyloidosis. This information has provided clinicians with the knowledge to enhance their awareness of a diagnosis of amyloidosis and gives recommendations for appropriate supportive care.
Pioneering of liver transplantation for patients with familial amyloidosis in collaboration with surgeons at the Lahey Clinic.
Pioneering of the use of high dose chemotherapy and autologous stem cell transplantation for patients with AL amyloidosis. This treatment has become the standard first line therapy for AL amyloidosis and has changed the median survival from 12 months to more than 5 years for suitable patients.
Investigation of the use of novel agents for treatment of AL amyloidosis, including immunomodulators and proteasome inhibitors, in collaboration with biotech companies and other centers.