Call Us: (314) 514-3500
PrintEmailBookmark and Share

Bio

Yousef Abu-Amer, PhD

Yousef Abu-Amer, PhD
Professor

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.

Background
Scientific staff, Shriners Hospital for Children, March 2001-Present; Associate Professor of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO., July 1999-Present; Assistant professor of Cell Biology and Physiology (Joint appointment), Washington University School of Medicine, St. Louis, MO., Jan 2002-Present; Instructor, Department of Pathology, Washington University School of Medicine, St. Louis, MO., Jan. 1998- Jun 1999

Awards
Ph.D. Fellowship - Kraut Endowment Fund, 1991-1993; Young Investigator Award for outstanding research, American Society for Bone and Mineral Research, 1995; Barnes-Jewish Hospital Foundation Award, 1996; Barnes-Jewish Hospital Foundation Award, 1997; Barnes-Jewish Hospital Foundation Award, 1998; The John Haddad Investigator Award for Outstanding Research, 1998; Arthritis Investigator Award, 1999-2002; Monsanto/Searle/Washington Univ Award, 1999-2000; New Investigator Recognition Award, 2000; Travel Award, American Society for Bone and Mineral Research, 2000; Medical research peer review program, Department of Veteran Affairs, 2001; AAOS/ORS Young Investigator Kappa Delta Award for outstanding research, 2002; NIH grant entitled, "Regulatory Mechanisms in Implant-Induced Osteolysis" (2004-2009)

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

Request an Appointment

* Patient's First Name
* Patient's Last Name
* Email Address
*Required Field

Resources


Abu-Amer Lab

Orthopaedic Research Society

Orthopaedic Research & Education Foundation

Orthopaedic Research

National Institutes of Health

DISCLAIMER:

The Department of Orthopaedic Surgery at Washington University School of Medicine in St. Louis has no control over third-party websites and does not review such websites. The university disclaims any responsibility for the content of third-party websites and the use of any information on these sites.