Zeljko Bosnjak Lab
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
Bosnjak Lab Members
Tarun Pant, BS
Role/Responsibilities/Research Interests: Student, Stem Cell Biology, Diabetic Cardiomyopathy
Dana B Murphy, BS
Role/Responsibilities/Research Interests: Collaborator, Stem Cell Biology
Roland James, MS
Recent Publications
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(Liu X, Chu H, Ji Y, Bosnjak Z, Ao H, Li T.) Diabetes Metab Syndr Obes. 2022;15:141-153 PMID: 35046685 PMCID: PMC8763208 01/21/2022
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(Pant T, DiStefano JK, Logan S, Bosnjak ZJ.) Anesth Analg. 2021 06 01;132(6):1614-1625 PMID: 33332892 PMCID: PMC8154629 SCOPUS ID: 2-s2.0-85106164112 12/18/2020
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(Perry TR, Roberts ML, Sunkara B, Maddula R, McLeish T, Gomez J, Lucas J, Rayan D, Patel S, Liang M, Bosnjak ZJ, Brown SA.) Curr Oncol Rep. 2021 05 03;23(7):77 PMID: 33937943 PMCID: PMC8088904 SCOPUS ID: 2-s2.0-85105159465 05/04/2021
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Biphasic effect of metformin on human cardiac energetics.
(Emelyanova L, Bai X, Yan Y, Bosnjak ZJ, Kress D, Warner C, Kroboth S, Rudic T, Kaushik S, Stoeckl E, Ross GR, Rizvi F, Tajik AJ, Jahangir A.) Transl Res. 2021 03;229:5-23 PMID: 33045408 SCOPUS ID: 2-s2.0-85095776755 10/13/2020
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(Pant T, Dhanasekaran A, Zhao M, Thorp EB, Forbess JM, Bosnjak ZJ, Benjamin IJ, Ge ZD.) Sci Rep. 2021 01 28;11(1):2571 PMID: 33510471 PMCID: PMC7843621 SCOPUS ID: 2-s2.0-85100002752 01/30/2021
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(Sepac A, Bosnjak ZJ, Seiwerth S, Sikiric S, Dzombeta TR, Kulic A, Karsaj JM, Sedlic F.) Int J Dev Biol. 2021;65(10-11-12):537-543 PMID: 35112709 SCOPUS ID: 2-s2.0-85123974351 02/04/2022
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(Pant T, Juric M, Bosnjak ZJ, Dhanasekaran A.) Front Cardiovasc Med. 2021;8:737512 PMID: 34660740 PMCID: PMC8517144 10/19/2021
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(Chinn GA, Pearn ML, Vutskits L, Mintz CD, Loepke AW, Lee JJ, Chen J, Bosnjak ZJ, Brambrink AM, Jevtovic-Todorovic V, Sun LS, Sall JW.) Br J Anaesth. 2020 May;124(5):585-593 PMID: 32145876 PMCID: PMC7424895 SCOPUS ID: 2-s2.0-85081263289 03/09/2020
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(Pant T, Dhanasekaran A, Bai X, Zhao M, Thorp EB, Forbess JM, Bosnjak ZJ, Ge ZD.) Sci Rep. 2019 10 25;9(1):15345 PMID: 31653946 PMCID: PMC6814824 SCOPUS ID: 2-s2.0-85074150710 10/28/2019
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(Horikoshi Y, Yan Y, Terashvili M, Wells C, Horikoshi H, Fujita S, Bosnjak ZJ, Bai X.) Cells. 2019 09 17;8(9) PMID: 31533262 PMCID: PMC6769886 SCOPUS ID: 2-s2.0-85080144549 09/20/2019
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(Pant T, Mishra MK, Bai X, Ge ZD, Bosnjak ZJ, Dhanasekaran A.) Diab Vasc Dis Res. 2019 01;16(1):57-68 PMID: 30482051 SCOPUS ID: 2-s2.0-85058938678 11/30/2018
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Current status and strategies of long noncoding RNA research for diabetic cardiomyopathy.
(Pant T, Dhanasekaran A, Fang J, Bai X, Bosnjak ZJ, Liang M, Ge ZD.) BMC Cardiovasc Disord. 2018 10 20;18(1):197 PMID: 30342478 PMCID: PMC6196023 SCOPUS ID: 2-s2.0-85055075405 10/22/2018