William Lee
Associate Professor, Dept of Medicine

Cancer Biology Program

Address

312 Biomedical Rsch Bldg (BRB) II/III
421 Curie Boulevard
Philadelphia, PA 19104

Office tel.: 215 898-0258
Lab tel.: 215 898-0259, 0260
Fax: 215 573-7912
E-mail: leemingf@mail.med.upenn.edu


EDUCATION

University of Chicago: BS (Biochemistry), 1969.

University of Chicago: PhD (Pathology/Immunology), 1974.

University of Chicago: MD (Medicine), 1975.

Research Interests

• Tumor angiogenesis, tumor physiology, antiangiogenesis tumor therapy, noninvasive tumor imaging.

Key words: cancer, angiogenesis, experimental therapy.

Search PubMed for articles

Description of Research

The requirement during tumor growth for blood perfusion and a vasculature that supports it has led us to study vascular development in tumors, antiangiogenic approaches to cancer therapy, and the tumor metabolic and physiologic consequences of this therapy. Our studies have identified an ordered series of tumor vessel developmental and maturation events not unlike that described during physiologic angiogenesis. Tumor vessel maturation affects the response to antiangiogenic agents inasmuch as more mature vessels, characterized by pericyte coverage of the vascular endothelial cells, are relatively resistant to these agents while less mature vessels are relatively susceptible. The loss of vessels with therapy results in or worsens tumor ischemia and ischemic cell death, which is the mechanism underlying tumor growth control. These findings have led us to develop autochthonous murine tumor models that more closely recapitulate the vasculature in human cancers, which have a more mature vascular profile and may be more resistant to antiangiogenic therapy than commonly used transplanted mouse tumors. We are identifying signal transduction pathways activated in vascular endothelial cells in tumors that correlate with angiogenesis, vessel maturation and regression during therapy, so that we can assign molecular signatures to these vascular events. Finally, we are seeking noninvasive ways to evaluate events and outcomes of antivascular therapy. These efforts are in collaboration with laboratories using ultrasound, magnetic resonance, radionuclide and optical techniques to image hemodynamic, cellular and physiological events in tumors and have clinical implications and applications.

RECENT PUBLICATIONS

Umamheswar D, Poptani H, Feldman M, Nadal-Desbarats L, Gee MS, Lee WMF, Reddy R, Leigh JS and Glickson JD: Quantitative Magnetic Resonance Imaging of RIF-1 tumors in vivo: Detection of early response to cyclophosphamide therapy. Canc. Res. 61: 7747-7753. 2001.

Lee JC, Kim DC, Gee MS, Saunders HM, Sehgal CM, Feldman MD, Ross SR and Lee WMF: Interleukin-12 inhibits angiogenesis and growth of transplanted but not in situ mouse mammary tumor virus (MMTV)-induced mammary carcinomas. Canc. Res. 62: 747-755. 2002.

Gee MS, Procopio WN, Makonnen S, Feldman MD, Yeilding NM and Lee WMF: Tumor vessel development and maturation impose limits on the effectiveness of antivascular therapy. Am. J. Pathol. 162:183-193, 2003.

Gee MS and Lee WMF: The role of tumor oxygenation in vascular and clinical response to angiogenesis inhibition. Adv. Exp. Med. Biol. 510:1-5, 2003.

Kamotani Y, Lee WMF, Arger PH, Cary TW, Sehgal CM: Multigated contrast enhanced power Doppler to measure blood flow in mice tumors. Ultrasound in Med. Biol., In Press, 2003.

Lab

Rotation Projects

Please contact Dr. Lee for current rotation projects.

Lab personnel:

Danielle Murphy
Jeff Tsai
Lisa Ziemer
Sosina Makonnen