James Varani, Ph.D.
Professor of Pathology
Campus Address:
M4224 MSI 0602
1301 Catherine Street
Ann Arbor, Michigan 48109-0602
Phone: 734/764-3190
varani@umich.edu
Annual Report | Biography | Clinical Interests | Research Interests
Departmental Annual Report
Brief Biography
Dr. Varani received his undergraduate degree from St. John's University in Collegeville, Minnesota and his Ph.D. at the University of North Dakota in 1974. After Post-Doctoral work at the University of Connecticut, he came to the University of Michigan as an Assistant Professor in 1980. He was promoted to Associate Professor in 1985 and became a Full Professor in 1991.
Dr. Varani was the Director of the University of Michigan Cancer Center Program, "Tumor Cell Metastasis and the Extracellular Matrix" from 1985-1997. Dr. Varani has research interests in skin biology and cancer invasion. In addition, he is a member of the Editorial Board of Invasion and Metastasis and frequent reviewer for other scientific journals.
Clinical Interests
Pathology, Skin Biology, Extracellular Matrix, Matrix
Research Interests
Metalloproteinase, Cancer Invasion
Research activities in our laboratory are focused on understanding the process of cancer cell invasion. For the most part, human squamous epithelial cell tumors are used as a model. In their clinical setting, these tumors demonstrate significant local invasion accompanied by a large amount of local tissue destruction. Using a combination of organ culture and cell culture models, our work has demonstrated that local invasion is associated with altered expression of a collection of tumor cell properties. The invading cells demonstrate a higher proliferative index than their non-invading counterparts. This is accompanied by enhanced motility, increased synthesis of basement membrane components and increased release of both serine and metalloproteinases. Present studies are utilizing the organ culture model of invasion in an effort to directly demonstrate the role of each of these tumor cell properties in invasion. Monoclonal and polyclonal antibodies, antisense oligonucleotides, proteolytic enzyme inhibitors are all being examined in this model. In addition, cells which have been genetically-altered to express differential amounts of extracellular matrix components are also being used. It is hoped that these studies will lead to an understanding of the role of each of these tumor cell properties in the invasion process.
A second research focus in our laboratory is on mechanisms of aging in skin. Again, we are using a combination of intact human skin, skin organ culture and monolayer cultures of the major components of skin to address mechanisms of natural aging and mechanisms of photoaging. Although once thought to reflect to entirely unrelated processes, it is now believed that in both there is 1)a loss of viability in the major cellular compartments of skin;2)reduced growth capacity of the remaining cells and 3)and altered phenotype (decreased matrix synthesis and increased matrix degradation) as compared to the phenotype of cells that are chronologically young and which have not been exposed to excessive ultraviolet light.