BIOSKETCH AND RESEARCH INTERESTS

Dr. Glenn C. Rowe received his B.S. in Biology from Brandeis University (2001) and his Ph.D. in Molecular, Cellular and Developmental Biology from Yale University (2007) where he studied the transcriptional regulation of factors that control bone and adipose tissue homeostasis. He completed his post-doctoral training at the Beth Israel Deaconess Medical Center, where his work focused on the role of transcriptional coactivators in regulating mitochondrial metabolism.

He joined the University of Alabama at Birmingham faculty in 2014 where he is currently Assistant Professor of Medicine in the Division of Cardiovascular Disease. His research interest focuses on understanding the cellular and molecular mechanisms underlying metabolism in the cardiovascular and musculoskeletal system. Dr. Rowe has a K01 Career Development award through the NIH-NIAMS, and is also a recent recipient of the UAB Pittman Scholar Award (2016).

The research interest of the Rowe laboratory focuses on understanding the molecular pathways that influence mitochondrial metabolism in response to diet and exercise, in order to improve mitochondrial function and reduce the deleterious effects of the metabolic syndrome.

Specifically, the lab studies the PGC-1 family of transcriptional coactivators and the molecular pathways they regulate in striated muscle to maintain normal mitochondrial function (including biogenesis, oxidative capacity and dynamics) and normal metabolic function. The laboratory utilizes a variety of molecular techniques, cell-based assays as well as genetically modified mouse models to understand the molecular mechanisms that control mitochondrial function.

Projects in the lab revolve around the following areas 1.) the study of mitochondrial dynamics in response to exercise, 2.) the effect of exercise on angiogenesis and mitochondrial metabolism, 3.) the characterization of new regulators of mitochondrial metabolism in striated muscle and 4.) contribution of mitochondrial function to whole body energy homeostasis.

ABSTRACT

Rationale: Mechanisms of angiogenesis in skeletal muscle remain poorly understood. Efforts to induce physiological angiogenesis hold promise for the treatment of diabetic microvascular disease and peripheral artery disease but are hindered by the complexity of physiological angiogenesis and by the poor angiogenic response of aged and patients with diabetes mellitus. To date, the best therapy for diabetic vascular disease remains exercise, often a challenging option for patients with leg pain. Peroxisome proliferation activator receptor-γ coactivator-1α (PGC-1α), a powerful regulator of metabolism, mediates exercise-induced angiogenesis in skeletal muscle.

Objective: To test whether, and how, PGC-1α can induce functional angiogenesis in adult skeletal muscle.

Methods and Results: Here, we show that muscle PGC-1α robustly induces functional angiogenesis in adult, aged, and diabetic mice. The process involves the orchestration of numerous cell types and leads to patent, non-leaky, properly organized, and functional nascent vessels. These findings contrast sharply with the disorganized vasculature elicited by induction of vascular endothelial growth factor alone. Bioinformatic analyses revealed that PGC-1α induces the secretion of secreted phosphoprotein 1 and the recruitment of macrophages. Secreted phosphoprotein 1 stimulates macrophages to secrete monocyte chemoattractant protein-1, which then activates adjacent endothelial cells, pericytes, and smooth muscle cells. In contrast, induction of PGC-1α in secreted phosphoprotein 1−/− mice leads to immature capillarization and blunted arteriolarization. Finally, adenoviral delivery of PGC-1α into skeletal muscle of either young or old and diabetic mice improved the recovery of blood flow in the murine hindlimb ischemia model of peripheral artery disease.

Conclusions: PGC-1α drives functional angiogenesis in skeletal muscle and likely recapitulates the complex physiological angiogenesis elicited by exercise. (Circ Res. 2014;115:504-517.)

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