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Biography

Our laboratory is focused on understanding the regulation and function of the vacuolar ATPases (V-ATPases) in normal and disease processes. The V-ATPases are a family of ATP-driven proton pumps which function in such processes as intracellular membrane traffic, bone resorption and renal acidification, as well as in many disease processes, including viral infection, bone disease and cancer. Our laboratory is employing a variety of biochemical, genetic and cell biological approaches to understand how assembly of the V-ATPases is regulated in mammalian cells and the role that V-ATPases play in nutrient sensing and energy homeostasis. In particular, we are interested in their role in controlling two central regulators of cell growth and metabolism, namely AMPK and mTOR. We are also investigating the role of V-ATPases in tumor cell invasion and survival using both in vitro cell culture models and in vivo mouse models, with the ultimate aim of developing therapeutic agents to inhibit tumor growth and metastasis.

Education

• BS, Biology & Chemistry, California Institute of Technology
• PhD, Biochemistry & Molecular Biology, Harvard University
• Postdoctoral Training, Harvard University

Research synopsis

Our laboratory is focused on understanding the regulation and function of the vacuolar ATPases (V-ATPases) in normal and disease processes. The V-ATPases are a family of ATP-driven proton pumps which function in such processes as intracellular membrane traffic, bone resorption and renal acidification, as well as in many disease processes, including viral infection, bone disease and cancer. Our laboratory is employing a variety of biochemical, genetic and cell biological approaches to understand how assembly of the V-ATPases is regulated in mammalian cells and the role that V-ATPases play in nutrient sensing and energy homeostasis. In particular, we are interested in their role in controlling two central regulators of cell growth and metabolism, namely AMPK and mTOR. We are also investigating the role of V-ATPases in tumor cell invasion and survival using both in vitro cell culture models and in vivo mouse models, with the ultimate aim of developing therapeutic agents to inhibit tumor growth and metastasis.

Publications

McGuire C, Stransky L, Cotter K, Forgac M. 2017. Regulation of V-ATPase activity. Front Biosci. 22:609-622.

Cotter K, Liberman R, Sun-Wada G, Wada Y, Sgroi D, Naber S, Brown D, Breton S, Forgac M. 2016. The a3 isoform of subunit a of the vacuolar ATPase localizes to the plasma membrane of invasive breast tumor cells and is overexpressed in human breast cancer. Oncotarget Epub ahead of print.

Stransky L, Cotter K, Forgac M. 2016. The Function of V-ATPases in cancer. Physiol Rev. 96: 1071-1091.

McGuire C, Cotter K, Stransky L, Forgac M. 2016. Regulation of V-ATPase assembly and function of V-ATPases in tumor cell invasiveness. Biochim Biophys Acta Epub ahead of print.

Cotter K, Stransky L, McGuire C, Forgac M. 2015. Recent insights into the structure, regulation, and function of the V-ATPases. Trends Biochem Sci. 40: 611-622.

Stransky LA, Forgac M. 2015. Amino acid availability modulates vacuolar H+-ATPase assembly. J Biol. Chem. 290: 27360-27369.