The overall theme of this basic and clinical research program, entitled """"""""Proteins in Multiple Myeloma and Related Blood Diseases"""""""", involves two major areas that include: I. The acquisition of information regarding human antibody structure and diversity through studies of the immunochemical, structural, physicochemical, genetic, and functional properties of monoclonal Igs found in patients with malignant immunoproliferative diseases; and II. The determination of the biological relevance of this information. These accomplishments have resulted in the formulation of a multidisciplinary research plan organized into two tactical areas - Diagnostic Strategies and Therapeutic Strategies - that are designed to improve the outcome of patients with these medically devastating and presently incurable illnesses. The planned Diagnostic Strategies involve the development of novel means to stage these diseases immunologically, pathologically, and radiographically. The proposed Therapeutic Strategies include a three-pronged attack designed to inhibit Bence Jones protein synthesis, to block the aggregation or tissue-binding of these components, and to effect the removal of pathologic light-chain deposits. The information gleaned from this research should be relevant to a wide spectrum of disorders associated with abnormal protein deposition.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Pathology A Study Section (PTHA)
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University of Tennessee Knoxville
Internal Medicine/Medicine
Schools of Medicine
United States
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Murphy, C; Wang, S; Kestler, D et al. (2011) Leukocyte chemotactic factor 2 (LECT2)-associated renal amyloidosis. Amyloid 18 Suppl 1:223-5
Murphy, C; Wang, S; Kestler, D et al. (2011) Vesicular senile systemic amyloidosis. Amyloid 18 Suppl 1:178-9
Murphy, C; Eulitz, D; Weiss, D et al. (2011) Light chain deamidation in AL? amyloid-associated protein. Amyloid 18 Suppl 1:27-8
Davern, S; Murphy, C L; O'Neill, H et al. (2011) Effect of lysine modification on the stability and cellular binding of human amyloidogenic light chains. Biochim Biophys Acta 1812:32-40
Murphy, C; Wang, S; Macy, S et al. (2011) Nature of os labrum-associated amyloid deposits. Amyloid 18 Suppl 1:206-7
Murphy, C; Kestler, D; Weiss, D et al. (2011) Non-hereditary apolipoprotein AI-associated pulmonary amyloid. Amyloid 18 Suppl 1:219-20
Phipps, Jonathan E; Kestler, Daniel P; Foster, James S et al. (2010) Inhibition of pathologic immunoglobulin-free light chain production by small interfering RNA molecules. Exp Hematol 38:1006-13
Larsen, Christopher P; Walker, Patrick D; Weiss, Deborah T et al. (2010) Prevalence and morphology of leukocyte chemotactic factor 2-associated amyloid in renal biopsies. Kidney Int 77:816-9
Murphy, Charles L; Wang, Shuching; Kestler, Daniel et al. (2010) Leukocyte chemotactic factor 2 (LECT2)-associated renal amyloidosis: a case series. Am J Kidney Dis 56:1100-7
Wall, Jonathan S; Kennel, Stephen J; Stuckey, Alan C et al. (2010) Radioimmunodetection of amyloid deposits in patients with AL amyloidosis. Blood 116:2241-4

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