Cancer is the second leading cause of death in the U.S., and novel therapeutics are of great need. Centrosomes are cellular microtubule organizing centers that are important for the faithful division of chromosomes during mitosis and are commonly dysregulated in cancer. Most human tumors have cells with centrosome amplification, or an abnormally elevated number of centrosomes. As a result of centrosome amplification, cancer cells can undergo asymmetric cell division, leading to chromosomal instability and aneuploidy, which is a source of genetic diversity that allows cancer to evolve and evade therapies. However, it is unclear how centrosome amplification arises, how it affects patient outcomes, and how it affects migration and metastatic potential. The overarching goal of this proposed research is to understand how centrosomes are dysregulated in cancer and to investigate the subsequent cellular and clinical consequences. The research proposed herein will enhance our knowledge of centrosome amplification in cancer, especially cancer cell division and migration, and potentially identify novel ways to target cancer cells with centrosome amplification.

Public Health Relevance

Centrosomes are components of the cell that are important for the correct separation of genetic material during cell division, and cancer cells of nearly all human tumors have centrosome amplification, or an abnormally elevated number of centrosomes. The proposed research will investigate how centrosomes are duplicated and dysregulated in cancer and examine the cellular and clinical ramifications of centrosome amplification. This will improve our understanding of centrosome amplification in cancer with the goal of learning how to better treat cancer, the second leading cause of death in the U.S. and a disease whose prevalence is projected to increase sharply in the coming years.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Damico, Mark W
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Wisconsin Madison
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Denu, Ryan A (2018) Reported Biologic Differences in Breast Cancer by Race Due to Disparities in Screening. JAMA Oncol 4:883
Denu, Ryan A; Mendonca, Eneida A; Fost, Norman (2018) Potential yield of imminent death kidney donation. Am J Transplant 18:486-491
Denu, Ryan A; Shabbir, Maria; Nihal, Minakshi et al. (2018) Centriole Overduplication is the Predominant Mechanism Leading to Centrosome Amplification in Melanoma. Mol Cancer Res 16:517-527
Denu, Ryan A; Burkard, Mark E (2017) Synchronous Bilateral Breast Cancer in a Patient With Nager Syndrome. Clin Breast Cancer 17:e151-e153
Denu, Ryan A; Rosenberg, Stephen A; Howard, Steven P (2017) Familial Trigeminal Neuralgia Treated with Stereotactic Radiosurgery: A Case Report and Literature Review. J Radiat Oncol 6:149-152
Denu, Ryan A; Zasadil, Lauren M; Kanugh, Craig et al. (2016) Centrosome amplification induces high grade features and is prognostic of worse outcomes in breast cancer. BMC Cancer 16:47