The goal of the Barrow lab is to employ proteomic, genomic, and metabolomic techniques to investigate metabolic and bioenergetic pathways in order to identify novel therapeutic targets for the treatment of metabolic disorders. Our research interest centralizes around mitochondrial biology with a dual integrated focus.

Primary Research Focus- Mitochondrial disease: This group of diseases represents one of the most commonly inherited human diseases and results in death if uncorrected. There is no cure or effective therapy so the need therefore to develop novel therapeutics is absolutely critical. Our goal is to:

1. Investigate metabolic and bioenergetic pathways that become dysregulated in mitochondrial disease. The aim is to identify novel factors that can be exploited for therapeutic potential that would boost oxidative phosphorylation (OXPHOS) capacity—the major failing hallmark in mitochondrial disease and associated metabolic disorders.
2. As one of many examples, we have previously identified the protein BRD4 as a regulatory factor that controls mitochondrial bioenergetics (Molecular Cell, 2016). When BRD4 is inhibited by CRISPR technology in patient-derived cells with mutated mitochondria genomes (results in cell death), BRD4 ablation restores their bioenergetics capacity and promotes the complete survival of the patient cells. We will be detailing this mechanism in highly metabolic cells such as muscle.

Secondary Research Goal- Obesity and Metabolic Disease: The second focus of the Barrow lab relates to chronic disease and exploring mitochondrial biology in the context of obesity to unveil novel factors that can be targeted for therapy. The rate of obesity has continued to grow at alarming rates worldwide due to an increase in caloric consumption coupled with a shift to more sedentary lifestyles. While many treatments for obesity have targeted limiting caloric intake, increasing energy expenditure by targeting cellular bioenergetics in adipose tissue or skeletal muscle may be a promising alternative. Our goal is to:

1. Investigate pathways that can activate the thermogenic function of the mitochondria as a therapeutic option for obesity. Thermogenic brown and beige adipocytes, which are characterized by the expression of uncoupling protein 1 (UCP1) in the mitochondria, have attracted considerable attention for their potential anti-obesity and anti-diabetic properties.
2. We demonstrated previously that brown/beige adipose tissue-specific Yin-Yang 1 (YY1) transcription factor knockout mice are protected from diet-induced obesity and have increased whole body energy expenditure (Molecular Cell Biology, 2015). We will be using the YY1 platform to uncover novel targets for therapy using proteomic, metabolic and genomic approaches.