Andrew Wojtovich - Principal Investigator
University of Rochester Medical Center
575 Elmwood Ave., Box 711/604
Rochester, NY 14642
Laura Bahr - Technical Associate
Miriam Barnett- Graduate Student
Brandon Berry- Graduate Student
Adam Trewin- Post-doctoral Fellow
Alicia Wei - Undergraduate Student
The Wojtovich lab focuses on the roles of Reactive Oxygen Species (ROS) in mitochondrial physiology and stress signaling.
Mitochondria are central mediators of cell death and are a main site of ROS production. ROS contribute to cellular damage in many pathologic processes, such as neurodegenerative diseases and stroke. However, antioxidant treatments have been ineffective in clinical trials for diseases associated with increased oxidative damage. These clinical trials may have failed since mild levels of ROS are required to maintain cellular homeostasis. Moreover, ROS are emerging as signaling molecules that are required for the efficacy of several types of protective interventions. Thus, like many other physiological challenges, specific details such as dose, timing, and local environment contribute to ROS outcomes.
The Wojtovich lab uses model organisms and optogenetic tools to control the site and timing of ROS production. With these tools, they investigate complex ROS biology in order to gain a better understanding ROS on a nano-scale. The lab uses a wide variety of approaches and translates findings from C. elegans to mammals. The expected outcome is a framework for developing targeted antioxidant therapies to overcome the obstacles that have led to so many clinical trial failures for existing antioxidant drugs.
NIH R01 NS092558-01
“Mitochondrial ROS microdomains and neuronal ischemia”
This project melds the C. elegans genetic model system with novel optogenetic reagents to give us the ability to control ROS production with unprecedented precision. We aim to determine what factors make some ROS beneficial and other ROS toxic in the context of neuronal ischemic sensitivity and stress resistance. We will integrate our results with conserved stress response pathways, facilitating translation into a mammalian model system.
PubMed Publication List
Wojtovich AP, Smith CO, Urciuoli WR, Wang YT, Xia XM, Brookes PS, Nehrke K. 2016. Cardiac Slo2.1 is required for volatile anesthetic stimulation of K+ transport and anesthetic preconditioning. In Press
Raphemot R, Swale DR, Dadi PK, Jacobson DA, Cooper P, Wojtovich AP, Banerjee S, Nichols CG, Denton JS. 2014. Direct activation of β-cell KATP channels with a novel xanthine derivative. Molecular Pharmacology, 85: 858-865.
Wojtovich AP, Foster TH. 2014. Optogenetic control of ROS production. Redox Biology. 2: 368-376.
Wojtovich AP, Nadtochiy SM, Urciuoli WR, Smith CO, Grunnet M, Nehrke K, Brookes PS. 2013. A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel. PeerJ. 1:e48
Wojtovich AP, Urciuoli WR, Chatterjee S, Fisher AB, Nehrke K, Brookes PS. 2013. Kir6.2 is not the mitochondrial KATP channel but is required for cardioprotection by ischemic preconditioning. American Journal of Physiology - Heart and Circulatory Physiology. 304: H1439-1445.
Wojtovich AP, Smith CO, Haynes CM, Nehrke KW, Brookes PS. 2013. Physiological consequences of complex II inhibition for aging, disease, and the mKATP channel. Biochimica et Biophysica Acta. 1827: 598-611
Guo S, Olm-Shipman A, Walters A, Urciuoli WR, Devito S, Nadtochiy SM, Wojtovich AP, Brookes PS. 2012. A cell-based phenotypic assay to identify cardioprotective agents. Circulation Research. 110: 948-957
Wojtovich AP, DiStefano P, Sherman T, Brookes PS, Nehrke K. 2012. Mitochondrial ATP-sensitive potassium channel activity and hypoxic preconditioning are independent of an inwardly rectifying potassium channel subunit in Caenorhabditis elegans. FEBS Letters. 586: 428-434.
Wojtovich AP, Sherman TA, Nadtochiy SM, Urciuoli WR, Brookes PS, Nehrke K. 2011. SLO-2 is cytoprotective and contributes to mitochondrial potassium transport. PLoS One. 6: e28287.
Wojtovich AP, Nadtochiy SM, Brookes PS, Nehrke K. 2012. Ischemic preconditioning: the role of mitochondria and aging. Experimental Gerontology. 47: 1-7.