Zeljko Bosnjak Lab
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.
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
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
(Pant T, Dhanasekaran A, Bai X, Zhao M, Thorp EB, Forbess JM, Bosnjak ZJ, Ge ZD.) Sci Rep. 2019 Oct 25;9(1):15345 PMID: 31653946 PMCID: PMC6814824 SCOPUS ID: 2-s2.0-85074150710 10/28/2019
(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 09/20/2019
(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
(Terashvili M, Bosnjak ZJ.) J Cardiothorac Vasc Anesth. 2019 Jan;33(1):209-222 PMID: 30029992 PMCID: PMC6203676 07/22/2018
(Liu Y, Paterson M, Baumgardt SL, Irwin MG, Xia Z, Bosnjak ZJ, Ge ZD.) Cardiovasc Res. 2019 01 01;115(1):168-178 PMID: 29931049 PMCID: PMC6302266 06/23/2018
(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
(Jiang C, Logan S, Yan Y, Inagaki Y, Arzua T, Ma P, Lu S, Bosnjak ZJ, Bai X.) Sci Rep. 2018 09 21;8(1):14172 PMID: 30242182 PMCID: PMC6155049 SCOPUS ID: 2-s2.0-85053736036 09/23/2018
(Ge ZD, Li Y, Qiao S, Bai X, Warltier DC, Kersten JR, Bosnjak ZJ, Liang M.) Anesthesiology. 2018 01;128(1):117-129 PMID: 29040168 PMCID: PMC5726897 SCOPUS ID: 2-s2.0-85037993657 10/19/2017
(Soriano SG, Vutskits L, Jevtovic-Todorovic V, Hemmings HC, 2016 BJA Neurotoxicology and Neuroplasticity Study Group.) Br J Anaesth. 2017 09 01;119(3):443-447 PMID: 28969326 PMCID: PMC6172966 10/04/2017
(Liu Y, Yan Y, Inagaki Y, Logan S, Bosnjak ZJ, Bai X.) Anesth Analg. 2017 07;125(1):241-254 PMID: 28622174 PMCID: PMC5484590 SCOPUS ID: 2-s2.0-85020541161 06/18/2017
(Bosnjak ZJ, Ge ZD.) F1000Res. 2017;6:928 PMID: 28690837 PMCID: PMC5482336 07/12/2017
(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 Mar 04 PMID: 32145876 03/09/2020