Chirgwin Lab

Indiana University Indianapolis

INTERNAL MEDICINE/MEDICINE

Indianapolis · United States

NIH-funded
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NIH R01 · 2024

Manipulating the N-end Rule Protein Degradation Pathway to Build Bone and Decrease Tumor Growth in Multiple Myeloma Bone Disease

Project Summary/Abstract Multiple Myeloma (MM) causes devastating bone destruction and protracted suppression of bone formation that markedly increases fracture risk, impacts mortality and contributes to MM cell drug resistance. MM bone lesions rarely heal in most patients, so that severe bone pain and fracture risk persist. Currently, there are no safe bone anabolic agents approved for MM bone disease (MMBD). We showed that the multi-domain protein p62 (sequestosome-1) is a major contributor to MMBD through its two major functions. It is a signaling hub for multiple signaling pathways that increase MM cell growth, bone destruction OB suppression in MM. p62 also mediates pro-survival…

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