The research interests of Jeffrey L. Salisbury, Ph.D., in cancer biology are focused on the origin and role of genomic instability in tumor progression.
Early on, Dr. Salisbury was fortunate to do pioneering studies that led to discovery of the protein centrin, which at the time was one of only a handful of centrosome proteins to be identified. Dr. Salisbury and his colleagues were the first to clone two of the human centrin genes and establish the crystal structure for this protein. Dr. Salisbury's group established centrin as an important calcium-sensitive regulator of centrosome behavior.
Using comparative proteomics, reverse genetics, and molecular and cell biology techniques, Dr. Salisbury's group helped to define the cell biology and molecular mechanisms that control centrosome dynamics and centriole duplication. His research program has a longstanding emphasis on regulation of centrosome dynamics during the cell cycle, as well as centrosome amplification and genomic instability in breast cancer.
Along with several other laboratories, Dr. Salisbury's lab was fortunate to "rediscover" contemporary evidence for Theodor Boveri's early suggestion for the role of centrosome defects in the origin of chromosomal instability and aneuploidy in cancer. This occurred when his research group first demonstrated centrosome amplification in human breast tumors and cultured human tumor cells. More recently, the study of genomic instability in cancer brought his research into the field of DNA damage repair.
Cell cycle control and its disruption in cancer
Genomic instability and tumor progression
Control of centrosome duplication and centrosome amplification in cancer
Primary cilia function in normal cells and its disruption in human disease processes
Electron microscopy as a means to study the cellular and sub-cellular processes in normal and disease states
Significance to patient care
Understanding the basic mechanisms by which genomic instability arises during tumor progression is key to the development of effective management strategies for cancer. Studies by Dr. Salisbury and his team have shown that one mechanism common to many cancers is the formation of multipolar mitotic spindles leading to aneuploidy, which is characterized by changes in chromosome number and distribution.
Dr. Salisbury's recent studies have shown that a unique population of cells within tumors that have stem cell-like properties show both a particular resistance to common chemotherapy strategies and also are uniquely stable against developing genomic instability.
Importantly, his team has found that these cells are particularly susceptible to a combination of treatments that include inhibitors of the mitotic kinase Aurora-A. These studies hold significant promise for the development of novel Aurora-A-targeted strategies for the treatment of cancer.
- Excellence in Teaching Recognition, Mayo Medical School
- Harold C. Bold Award, Phycological Society of America
- R.R. Bensley Award, American Association of Anatomists
- Editorial Board Member — Journal of Eukaryotic Microbiology, Journal of Histochemistry & Cytochemistry, Calcium Binding Proteins, International Journal of Oncology, Centrosome Research