Cardiovascular Center

Research Statement

Zeljko J. Bosnjak, PhD, FAHA, is Professor of Medicine and Physiology. He received his doctorate from the Medical College of Wisconsin and has been continually funded by the NIH since 1981, including the current Program Project Grant. His research has been documented in more than 320 articles, reviews & book chapters, and is focused on patient stem cell-derived cardiac and neural cells. Dr. Bosnjak trained more than 100 pre-and postdoctoral fellows and served on various committees at MCW. He was an editor of Anesthesiology, president of the Foundation for Anesthesia Education and Research, Academy of Research Mentors in Anesthesiology, and currently serves on many editorial boards. Dr. Bosnjak was a long-time member and the Chairman of the NIH Surgery, Anesthesia, and Trauma Study Section; member of the National Advisory General Medical Sciences Council; and continues to serve on study sections for the NIH.

Current Projects

We are in the 15th year of our Program Project Grant: “Mechanisms of Anesthetic Cardioprotection”. The central theme of this PPG is to gain fundamental insight into the mechanisms responsible for greater susceptibility of diabetic hearts to ischemia-reperfusion injury using both patient-derived cardiomyocytes and diabetic animals. We use anesthetics to test the ability of diabetic animals and human cardiomyocytes to be protected against ischemia-reperfusion injury for the future development of novel cardioprotective strategies for the diabetic heart. Our hypothesis is that diabetes undermines cardioprotection through actions on cardiomyocytes that are both environmental and cellular in origin. Our translational approach includes in vivo diabetic animal models, isolated animal heart preparations, isolated animal cardiomyocytes and mitochondria, computer simulations and modeling of mitochondrial and cellular function in anesthetic cardioprotection, and finally, human cardiomyocytes derived from disease-specific induced pluripotent stem cells. In addition to Dr. Bosnjak as Program Director the Project Leaders are Drs. Zeljko Bosnjak, Mingyu Liang and Ranjan Dash.

Another study involves the measurements of Biomarkers involved in anesthetic-induced neurotoxicity. This research aims to identify circulating biomarkers that may help identify children, who are at risk for developing learning and memory impairment due to surgery. Since previous studies suggest that children may develop cognitive and behavioral impairment if they are exposed to longer period of anesthesia before the age of 4 years, our study will compare two groups of pediatric patients: Less than 4 years of age and 4-17 years of age. Each group will have 30 patients with ten of them having surgery duration of less than 1h; ten patients having non-cardiac surgery of over 2h; and 10 patients having cardiac surgery of over 2h duration. We will measure serum biomarkers for the early detection of anesthetic-induced neurotoxicity, especially during the most sensitive developmental brain growth spurt period.

In addition, we are examining the cardiotoxicity of breast cancer chemotherapeutic agents, doxorubicin (Adriamycin) on human stem cell-derived cardiomyocytes (hiPSC-CM) from healthy and type 2 diabetic patients. Although clinicians are aware of doxorubicin-induced cardiomyopathy and consistently make efforts to minimize such dose-dependent toxicity, the condition remains a major clinical problem. Previous studies have shown that hiPSC-CMs from individuals who experienced doxorubicin-induced cardiotoxicity reproducibly showed greater sensitivity to doxorubicin toxicity than did hiPSC-CMs from treated patients who did not exhibit toxicity.

Zeljko Bosnjak, PhD

Professor, Medicine
zbosnjak@mcw.edu