My career goal is to understand how human cells divide and to use this to treat breast cancer. My research group has two major projects. First, we are using chemical biology and human cell gene editing to understand how mitotic kinases control human cell division. This is challenging because protein kinases have many substrates and concordant functions, but they occur all within ~60 minutes of human cell division. By combining chemical and genetic tools, we have begun to unravel the complicated functions of Plk1 and link these functions to the cognate molecular events. We are now applying this system to understand the function of additional mitotic kinases in both human epithelial cells and human induced pluripotent stem cells.
A second major project seeks to identify and treat polyploid breast cancers. Polyploidy is the presence of extra chromosome sets, and is thought to arise from failed cell division. We have discovered that polyploid breast cancers are associated with worse cancer outcomes in patients. We have performed screens to identify novel chemicals and drug targets that can specifically disrupt growth of polyploid cells. Because such cells occur rarely in proliferating compartments in adult humans, these approaches may be useful for treating polyploid breast cancers. Our screens are unique in that we incorporate information from genetically diverse polyploid and diploid cancer types to ensure our hits have external validity, while at the same time verifying that these effects are specific to polyploidy per se using paired diploid-polyploid cell types. By doing so, we hope to identify effective treatments for breast cancers that arise from failed cell divisions.
- Identified drugs and drug targets that are specifically required in high-ploidy cancers
Honors & Awards
- 2012 Puestow Research Award for Significant Research Contribution Toward Advancing the Field of Medicine. Department of Medicine, University of Wisconsin.
- 2012 ACRIN-ECOG Translational Research Award, Eastern Cooperative Oncology Group, Hollywood FL.
- 2012 Novel and Newsworthy Presentation (1 of 12 selected), American Society of Cell Biology Annual Meeting, San Francisco CA
- 2013 UW Health Patient Experience Physician Champion Award (awarded to UW Health Physicians who score among the top 5% in patient surveys)
- 2014 Finalist, Burroughs Wellcome Fund Innovation in Regulatory Science Awards
- Kim H, Guo F, Brahma S, Xing Y, Burkard ME. Centralspindlin assembly and two phosphorylations on MgcRacGAP by Polo-like kinase 1 initiate Ect2 binding in early cytokinesis. Cell Cycle 2014,13(19)2952-61. PMCID: PMC Journal *in Process.
- Zasadil LM, Andersen KA, Yeum D, Rocque GB, Wilke LG, Tevaarwerk AJ, Raines RT, Burkard ME, Weaver BA. Cytotoxicity of Paclitaxel in Breast Cancer is due to Chromosome Missegregation on Multipolar Spindles. Sci Transl Med. 2014 Mar 26;6(229):229ra43. PMCID: PMC Journal * in Process
- Burkard ME, Wisinski KB, Njiaju UO, Donohue S, Hegeman R, Stella A, Mansky S, Shah V, Goggins T, Qamar R, Dietrich L, Kim K, Traynor AM, Tevaarwerk AJ. Feasibility of four cycles of docetaxel and cyclophosphamide every 14 days as an adjuvant regimen for breast cancer: A Wisconsin Oncology Network study. Clin Breast Cancer. 2013 Oct 26. pii: S1526-8209(13)00255-3. NIHMSID: NIHM540654.
- Choudhary A, Lera RF, Martowicz ML, Oxendine K, Laffin J, Weaver BA, Burkard ME. Interphase cytofission maintains genomic integrity of human cells after failed cytokinesis. Proc Natl Acad Sci USA, 2013 Aug 6; 110(32):13026-31. PMCID: PMC3740861.
- Lera RF, Burkard ME. High mitotic activity of Polo-like Kinase 1 is required for chromosome segregation and genomic integrity in human epithelial cells. J Biol Chem, 2012 Dec 14;287(51):42812-25. PMCID: PMC3525009.