A postdoctoral position is available immediately in the laboratory of Dr. Boyce, Department of Pathology and Laboratory Medicine and the Center for Musculoskeletal Research at the University of Rochester Medical Center, Rochester, New York, following the successful renewal of an NIH RO-1 grant that has been funded continuously since 1995. Dr. Boyce is a surgical pathologist specializing in the diagnosis of bone and soft tissue diseases and a basic scientist with an interest in the regulation of bone turnover in normal and pathologic conditions. Work in our lab has focused on the role of NF-kB signaling in the formation and activity of osteoclasts and osteoblasts, following our discovery >25 years ago that NF-kB positively regulates osteoclast formation. Current work focuses on the role of TRAF3/NF-kB in osteoclast precursors as a negative regulator of RANKL-induced osteoclast formation and also as a negative regulator of TGFb-induced inhibition of mesenchymal progenitor cell (MPC) differentiation into osteoblasts. Through this work, we have identified a novel subset of B cells that express RANKL and CXCR4 and found that their numbers are increased in the bone marrow (BM) of mice with TRAF3 conditionally deleted in osteoclast precursors and are the most abundant RANKL-expressing cells in BM of aging mice. We hypothesize that these cells are attracted to the BM during aging by MPCs that have increased expression of CCL12, a ligand for CXCR4, as a result of NF-kB-induced low-level chronic inflammation of aging, and cause age-related increased bone resorption. We plan to fully characterize these cells phenotypically using flow cytometry and single cell and bulk RNA-seq, map their locations in bone using a Fluidigm Hyperion CyTOF platform, and determine if: 1) they accumulate in BM of aging humans; 2) CXCR4 in B cells mediates their accumulation in the BM of aging mice by conditionally deleting CXCR4 in B cells; 3) TRAF3 expressed by MSCs regulates the accumulation of these B cells in BM by modulating SDF1 expression; 4) plerixafor (a CXCR4 inhibitor) prevents age-related osteoporosis by depleting RCBs from BM; 5) and if targeting plerixafor to bone by linking it to a bisphosphonate increases its efficacy and reduces its adverse effects.
EDUCATION AND EXPERIENCE REQUIRED
The applicants must have a PhD, MD or MD/PhD degree, be highly motivated with a strong motivation to work independently with good writing and oral communication skills. Prior experience in musculoskeletal skeletal research, histomorphometry and flow cytometry is preferred, and in single cell and bulk RNA-seq would be a plus.
APPLICATION REQUIREMENTS
To apply for this position, please email a cover letter and C.V. to:
brendan_boyce@urmc.rochester.edu
