WASHINGTON UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF MEDICINE

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The skeleton is the organ most commonly affected by metastatic cancer in humans. Mechanisms by which skeletal metastases are established are unclear; however, osteoclast activation plays a critical role in the pathogenesis of bone metastases. Our laboratory focuses on the molecular mechanisms through which tumor cells metastasize to bone. The projects in our laboratory include:

The role of beta 3 integrin in skeletal metastases

The beta 3 integrin subunit (β3) has been implicated in the development of metastases because of its critical role in osteoclastic bone resorption (αvβ3), and its role in platelets in tumor cell homing (αIIbβ3). We have established an in vivo model of bone metastasis using the osteolytic and osteoblastic tumor cell lines. To examine the role of the β3 integrins in skeletal metastases we utilize mice with a disruption of the β3 integrin subunit gene (β3-/-).

The role of Tax oncogene in skeletal metastases

HTLV I associated Adult T cell leukemia (ATLL) is distinctive for its high rate of osteolytic skeletal metastases and hypercalcemia. Expression of HTLV-1 Tax oncogene, under the regulation of the granzyme B promoter, results in tumors. We find that these mice also develop lytic bone lesions, a clinical feature of ATLL. Our laboratory studies the molecular mechanisms of Tax oncogene induced bone disease

The role of CXCR4 in bone metastasis

SDF-1 and its receptor CXCR-4 have been shown to be one mechanism by which blood cell precursors home to the bone. We hypothesize that the SDF-1/CXCR-4 interaction plays a role in tumor cell homing to bone as well. We are evaluating if the disruption of the CXCR-4/SDF-1 interaction can prevent bone metastasis in a murine model.

Information from these studies has been applied to developing novel therapeutic approaches for the prevention of bone metastasis in women with breast cancer.

Aspirin and APT102 in combination significantly decrease metastatic tumor burden in a murine tumor model. From: Uluckan O, Eagleton MC, Floyd DH, Morgan EA, Hirbe AC, Kramer M, Dowland N, Prior JL, Piwnica-Worms D, Jeong SS, Chen R, Weilbaecher K APT102, a novel adpase, cooperates with aspirin to disrupt bone metastasis in mice. J Cell Biochem 2008 Jul 1;104(4):1311-1323

Education

1987	BA, Harvard University, Cambridge, MA
1992	MD, Stanford University School of Medicine, Palo Alto, CA

Post-graduate Training

1992-94	Intern and Resident in Medicine, Assistant Clinical Instructor in Medicine, Stanford University Hospital, Stanford, CA
1994-98	Fellow in Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
1994-98	Clinical Fellow in Medicine, Brigham and Women's Hospital, Boston, MA

Academic Positions

1998-2000	Instructor in Medicine, Harvard Medical School, Boston, MA
2000-2008	Assistant Professor of Medicine, Washington University, St. Louis, MO
2000-2007	Assistant Professor of Pathology & Immunology, Washington University, St. Louis, MO
2003-2008	Assistant Professor of Cell Biology & Physiology, Washington University, St. Louis, MO
2008-present	Associate Professor of Medicine, Washington University, St. Louis, MO
2008-present	Associate Professor of Cell Biology & Physiology, Washington University, St. Louis, MO

University Committees

2000-present	Cellular Proliferation Program, Siteman Cancer Center
2000-present	Breast Oncology Focus Group, Siteman Cancer Center
2002-present	Oncology Fellowship Protocol Committee
2006-present	MD/MA Degree Granting Committee
2006-present	LCME Accreditation Committee
2007-present	WUSM Research Planning for Cancer Committee

Board Certification

1995-2005	Internal Medicine
1997	Medical Oncology

Honors & Awards

1986	Radcliffe Junior Science Prize
1987	Magna Cum Laude, Harvard University
1992	Dean's Award for Research, Stanford Medical School
1994	Housestaff Clinical Teaching Award, Stanford Medical School
2008	Elected to American Society for Clinical Investigation

Peer-review Committees

2003-present

Ad hoc reviewer, NIH: Pathology B Study Section, TPM Study Section

Professional Societies & Organizations

1998-present	American Society of Clinical Oncology
1999-present	American Society of Bone and Mineral Research (scientific committee member)
2005-present	Cancer and Bone Society (founding member and international meeting co-organizer)
2005-present	International Bone and Mineral Society (cancer and bone advisory committee)
2006-present	International Conference on Skeletal Complications of Malignancy (scientific advisory board)
2008-present	American Society for Clinical Investigation

• Updated: June 3, 2009
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