Mark Burkard, MD, PhD

Portrait of Mark Burkard, MD, PhD
Associate Professor
Medicine
Address: 
6059 WIMR
1111 Highland Ave
Madison, WI 53705
Telephone: 
(608) 262-2803
Focus Groups: 
Cancer Biology
Education: 
MD, University of Rochester
PhD, University of Rochester
Research Summary: 
Breast cancer and drug development
Research Detail: 

I am a chemical biologist and medical oncologist who specializes in the treatment of breast cancer. My career goal is to develop novel therapeutic strategies to treat breast cancer. I lead a research laboratory focused on using chemical biology to identify and validate mitotic protein kinases as breast cancer drug targets. My major research effort to date has focused on polo-like kinase 1 (Plk1), an essential protein kinase required for formation of mitotic spindles in dividing cells, cancer and non-cancer alike. I have developed a unique chemical-genetic system to study detailed function of Plk1 in human cells. This system allows chemical sensitivity to be genetically encoded so Plk1 can function can be interrogated with high temporal precision and genetic controls to ensure against off-target effects. Using this system, I was unable to uncover a novel function of Plk1 in late cell division and identify detailed mechanism. This approach can, in principle, be extended to any of ~500 kinases encoded in the human genome.

Our laboratory seeks to understand how protein kinases regulate human cell division and to use this knowledge to improve treatment of breast cancer. We have taken two approaches to the problem. First, we have used chemical genetics to identify function of protein kinases required for cell division, including Polo-like kinase 1. Chemical genetics overcomes the problem of specificity of kinase inhibitors and provide unique tools to identify functionally relevant kinase substrates. We are currently extending this system to other protein kinases involved in human cell division. Second, we identify unique characteristics of cancer cells (biomarkers) that make them susceptible to specific anticancer therapies. Our ultimate goal is to combine chemical genetics with biomarker analysis to develop validated kinase-targeted therapeutic approaches for all breast cancer types.

Selected Publications: 
Rocque G, Onitilo A, Engel J, Pettke E, Boshoven A, Kim K, Rishi S, Waack B, Wisinski KB, Tevaarwerk A, Burkard, ME. Adjuvant therapy for HER2+ breast cancer: practice, perception, and toxicity. Breast Cancer Res Treat 131:713-21, 2012. PMCID:PMC3329126
Tevaarwerk A, Burkard ME, Wisinski KB, Shafter MM, Davis LA, Gogineni J, Crone E, Hansen KE. Aromatase inhibitors and calcium absorption in early stage breast cancer. Breast Cancer Res Treat 134(1):245-51, 2012. PMCID:PMC3376688
Burkard ME, Santamaria A, Jallepalli PV. Enabling and disabling polo-like kinase 1 inhibition through chemical genetics. ACS Chem Biol 15;7(6):978-81, 2012. PMCID:PMC3376236
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 287 (51):42812-25, 2012. PMCID: PMC3525009.
Lera RF, Burkard ME. The final link: tapping the power of chemical genetics to connect the molecular and biologic functions of mitotic protein kinases. Molecules 17(10): 12172-86, 2012. PMCID: PMC3620603.
Burkard ME, Jallepalli PV. Validating cancer drug targets through chemical genetics. Biochim Biophys Acta 1806(2): 251-7, 2010. PMCID: PMC3028588
Burkard ME, Maciejowski J, Rodriguez-Bravo V, Repka M, Lowery DM, Clauser KR, Zhang C, Shokat KM, Carr SA, Yaffe MB, Jallpalli PV. Plk1 self-organization and priming phosphorylation of HsCYK-4 at the spindle midzone regulate the onset of division in human cells. PLOS Biol 7 (5): e1000111, 2009. PMCID: PMC2680336
Burkard ME, Randall CL, Larochelle S, Zhang C, Shokat KM, Fisher RP, Jallepalli PV. Chemical genetics reveals the requirement for Polo-like kinase 1 activity in positioning RhoA and triggering cytokinesis in human cells. Proc Natl Acad Sci USA 104:4383-8, 2007.
Znosko BM, Burkard ME, Krugh TR, and Turner DH. Molecular recognition in purine-rich internal loops: thermodynamic, structural, and dynamic consequences of purine for adenine substitutions in 5’(rGGCAAGCCU)2. Biochemistry 41:14978-87, 2002.
Znosko BM, Burkard ME, Schroeder SJ, Krugh TR, Turner DH. Sheared AantiAanti base pairs in a destabilizing 2x2 internal loop: the NMR structure of 5’(rGGCAAGCCU)2. Biochemistry 41:14969-77, 2002.