Yousef Abu-Amer

Yousef Abu-Amer, PhD

Professor

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(314) 514-3500

Hospital Affiliations

  • Barnes-Jewish Hospital

Academic Office Mailing Address

  • Washington University School of Medicine

    Campus Box 8233

    660 Euclid Avenue

    Saint Louis, MO 63110

Research Interests

Excessive osteoclast activity is the lead cause of bone loss diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, and osteolysis. Events leading to development of these diseases depend primarily on high and sustained secretion of pro-inflammatory cytokines that enhance osteoclast development and activity. The research in our laboratory focuses on identifying the molecular mechanisms of pro-inflammatory cytokines-induced osteoclast differentiation. We have delineated a novel pro-osteoclastic signaling pathway transmitted by tumor necrosis factor alpha (TNF) via its type-1 receptor (TNFR-1) in osteoclast precursor cells. This pathway leads to activation of the tyrosine kinase c-src, which then phosphorylates IkB on tyrosine 42 leading to NF-kB activation. Given that NF-kB is essential for osteoclast development, we have successfully utilized tyrosine 42-mutated IkB as a dominant-negative tool to block osteoclastogenesis, in vitro. Future experiments will test the inhibitory effect of DN-IkB in vivo. We are also engaged in investigating the possible molecular cross-talk between TNF receptors and the recently described osteoclastogenic receptor-activating NF-kB (RANK). Evidence points to the possibility that TNF and RANK signaling pathway orchestrate osteoclast differentiation and activation. In a different study, we have established that the T-lymphocyte secreted interleukin-4 inhibits NF-kB activation and osteoclast formation. This process is dependent upon activation of another transcription factor termed STAT6 (signal transducer and activator of transcription 6) which in this case acts a repressor of transcription. Once again, inhibition of NF-kB and osteoclastogenesis were achieved by introduction of STAT6 to osteoclast precursors. We are currently in the course of testing if STAT6 inhibits osteolysis in vivo. We also have established a serum-transfer model of rheumatoid arthritis. In this model, joint inflammation, swelling, NF-kB and MAP kinase activation occur in vivo within 48-post serum transfer. Bone erosion is established within 7 days. This model will be utilized to test if DN-IkB and STAT6 can alleviate inflammation and bone erosion. Dr. Abu Amer was recently awarded a 5 year grant from NIH/NIAMS for a project entitled, Regulatory Mechanisms of Implant-Induced Osteolysis. The project will investigate the molecular role of mitogen-activated protein kinases (MAPK) in osteolytic responses and advance therapeutic approaches for the treatment of inflammatory osteolysis.

Board Certifications

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Bachelors Degree

  • The Hebrew University, Biology

Masters Degree

  • The Hebrew University, Endocrinology and Cell Biology

Doctorate

  • Hubert H. Humphrey Center for Experimental Medicine and Cancer Research - The Hebrew University, Cell Biology

Fellowship

  • Pathology, Washington University School of Medicine

Honors and Awards:

  • 1995 Young Investigator Award for Outstanding Research, American Society for Bone and Mineral Research
  • 1998 The John Haddad Investigator Award for Outstanding Research
  • 1999 - 2002 Arthritis Investigator Award
  • 1999 - 2000 Monsanto/Searle/Washington University Award
  • 2000 New Investigator Recognition Award, Orthopaedic Research Society
  • 2000 Travel Award, American Society for Bone and Mineral Research
  • 2000 Member, Orthopaedic Research Society
  • 2002 AAOS/ORS Young Investigator Kappa Delta Award
  • 2004 Editorial Board, Journal of Bone and Mineral Research
  • 2004 Editorial Board, Journal of Calcified Tissue International

Make an Appointment

Dr. Abu-Amer’s Office Locations

BJC - Institute of Health

11th floor - RM 11614

Disclaimer

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