John Hogenesch, PhD, is a genome and circadian biologist focusing on the genetics of circadian timing in mammals. He discovered Bmal1, the master regulator of the mammalian clock, but also its paralog Bmal2, its partner Npas2, and the positive loop of the clock (Hogenesch et al., JBC, 1997; Hogenesch et al., PNAS, 1998; Hogenesch et al., J. Neurosci, 2000). Later, his lab characterized Rora/Rorb/Roc as key regulators of Bmal1 and circadian function (Sato et al., Neuron, 2004), discovered Chrono as a non-canonical repressor of Bmal1/Clock (Anafi et al., PLoS Biology, 2014), and Kpnb1 as a required transporter of the PER/CRY complex (Lee et al., Elife, 2015). The Hogenesch lab studies transcriptional outputs of the clock in animal models and humans (Panda et al., Cell, 2002, Hughes et al., PLoS Genetics, 2009, Zhang et al., PNAS, 2014; Anafi et al., PNAS, 2017; Ruben et al., Science Translational Medicine, 2018). This work is leading to a wealth of new opportunities in circadian medicine and has spurred community contributions, such as the public databases the Gene Atlas and Gene Wiki, CircaDB, and algorithms, including JTK, PSEA, MetaCycle, and CYCLOPS (Su et al., PNAS, 2004; Huss et al., NAR, 2010; Hughes et al., JBR, 2010; Pizarro et al., NAR, 2013; Zhang et al., JBR, 2014; and Wu et al., Bioinformatics, 2016; Anafi et al., PNAS, 2017).Together with collaborators at Cincinnati Children's ( David Smith, MD, PhD, Thomas Dye, MD, Kelly Byars, PsyD, Danielle Graef, PhD and Carlos Prada, MD), the Hogenesch lab is also characterizing genetic variation in syndromic and non-syndromic children with circadian sleep disorders.
Our research interests lie in the understanding of muscle contractile proteins associated with both normal and diseased function. More specifically, we focus on tropomyosin, a sarcomeric thin filament protein found in skeletal and cardiac muscle. Our research addresses the physiological significance of tropomyosin (Tm) isoforms with respect to sarcomeric function and their role in cardiac disease. Our approach utilizes transgenic and knockout mice to determine how the cardiac sarcomere and the heart undergo remodeling in response to different Tm isoforms and genetically-defined mutations that correspond to human hypertrophic and dilated cardiomyopathies. Our recent work examines how Tm phosphorylation influences sarcomeric performance and cardiac function, along with the molecular pathways that are activated by this process.