Faculty

Joel Buxbaum 
Professor
Head, Division of Research Rheumatology
TSRI - 1999

Joint Appointments 
The Keck Autoimmune Disease Center

Education 
1954-1958, B.S., Union College, Schenectady, New York
1958-1962, M.D., Tufts University School of Medicine, Boston, MA
1962-1963, Intern in Internal Medicine, University of Utah Affiliated Hospitals, Salt Lake City
1963-1964, Assistant Resident in Internal Medicine, University of Utah
1964-1965, Research Associate, NIH Malaria Project, NIAID
1965-1966, Deputy Chief of Medicine, USPHS Hospital, Savannah, GA
1966-1969, Research Fellow, Dr. E.C. Franklin, NYU School of Medicine
1969-1971, Special Fellow, Dr. M.D. Scharff, Albert Einstein College of Medicine, New York
1971-1973, Res. & Ed. Associate, New York V A Medical Center, N.Y.C., N.Y.
1980-1981, American Cancer Society Scholar in Cancer Research, L.Hood, Division of Biology, California Institute of Technology
1971-1977, Assistant Professor of Medicine, NYU School of Medicine
1977-1981, Associate Professor of Medicine, NYU School of Medicine
1981-1999, Professor of Medicine, NYU School of Medicine
1971-1999, Chief, Rheumatology Section, New York VA Medical Center
1971-1999, Director, Cell Biology Res. Lab., New York VA Medical Center
1976-1999, Graduate Faculty, Dept. of Pathology, NYU School of Medicine
1999-present, Professor, Department of Molecular and Experimental Medicine, TSRI
2001-present , Director, Division of Rheumatology Research, Head, Keck Autoimmune Disease
Center, Department of Molecular and Experimental Medicine, TSRI

Awards & Activities 
1980-1981, American Cancer Society Scholar in Cancer Research
1997-2000, Frank G. Spencer Fellow New York Affiliate American Heart Association
2000, Edward Bierman Lecturer Mid-Winter Conference on Controversies in Medicine;
Editorial Boards:
1993-Present, Amyloid, The Journal of Protein Folding Disorders
1988-1991, Arthritis and Rheumatism

Research Focus 
Molecular Basis of Acquired and Hereditary Human Disease

In the human amyloidoses, soluble proteins, synthesized and secreted from the cell, become insoluble in tissues with resultant organ compromise. The serum protein transthyretin is the precursor to the deposited protein in late-onset hereditary and acquired forms of neurologic, heart and kidney amyloidosis. We have established a disease model by creating a strain of mice carrying the human gene. In humans, amyloid deposition requires many years for initiation and progression. In our transgenic mice, by two years of age, a majority develop age-dependent deposition of the human protein in the heart and/or kidneys, a delay consistent with the late onset seen in humans. Prior to the appearance of Congophilic fibrils, the animals display less structured deposits that appear to be precursors to the amyloid fibrils. Analysis of this apparent in vivo folding intermediate should provide insight into the pathologic process responsible for the human disease. Our studies are designed to determine why deposition is age-dependent and what factors modulate the changes in protein conformation from the non-fibrillar to the fibrillar state.

Selected References 
Teng MH, Yin J, Vidal R, Ghiso J, Tagoe C, Gallo G and Buxbaum JN: Amyloid and non-fibrillar tissue deposits in animals transgenic for wild type human transthyretin: A possible model for senile systemic amyloidosis. Laboratory Investigation 81:385-396, 2001.

Buxbaum JN. Diseases of protein conformation: what do in vitro experiments tell us about the in vivo diseases? Trends in Biochemical Sciences 28 (11):585-92, 2003.

Reixach N, Deechongkit S, Foss T, Jiang X, Kelly JW, Buxbaum JN. Tissue damage in the amyloidoses: Transthyretin monomers and nonnative oligomers are the major cytotoxic species in tissue culture. Proc Natl Acad Sci (USA) 101(9):2817-2822, 2004.

Soares ML, Coelho T, Sousa A, Batalov S, Conceição I, Sales-Luís ML, Ritchie MD, Williams SM, Nievergelt CM, Schork NJ, Saraiva MJ, Buxbaum JN. Susceptibility and modifier genes in Portuguese transthyretin V30M amyloid polyneuropathy: complexity in a single gene disease. Hum. Mol. Gen. 14(4):543-553, 2005.