Research across clocks, transcriptomes, and medicine

Molecular Circadian Clock

Foundational work from the lab helped define the mammalian clock at the level of transcription factors and feedback architecture. This includes discovery and characterization of BMAL1/MOP3, NPAS2, and BMAL2, together with several related bHLH-PAS domain genes. Related early work identified HIF-2alpha. Later work involved mechanistic studies of how these factors regulate downstream transcription.

• Core clock transcription factors in mammalian systems.
• Feedback regulation and clock-controlled gene expression.
• Links between molecular output and physiology.

Selected publications: 1997 bHLH-PAS family paper · BMAL1 / MOP3 · RORA / RORE loop · CHRONO

Circadian Biology of Clocks

The lab has used genome-scale experimental designs to define the breadth of rhythmic transcription across tissues and organs. This work established the mammalian circadian transcriptome as a large, tissue-specific regulatory system rather than a narrow set of canonical clock genes.

• High-resolution temporal profiling of circadian transcription.
• Multi-organ analysis of rhythmic gene expression across the mouse body.
• Functional genomics approaches to identify clock modulators and mechanisms.

Selected publications: Gene Atlas · Harmonics of circadian gene transcription · Mouse organ atlas

Computational Methods and Public Resources

A major part of the lab’s scientific footprint is methodological. JTK_CYCLE, PSEA, MetaCycle, CYCLOPS, CYCLOPS2, and CircaDB were all built to make rhythmic data more interpretable, more reproducible, and more broadly usable by the field.

• JTK_CYCLE and MetaCycle for rhythmicity detection.
• PSEA for phase-structured pathway interpretation.
• CYCLOPS and CYCLOPS2 for recovering temporal order and addressing newer integration problems in unordered human datasets.
• CircaDB as a public gene-expression database for rhythmic biology.

Selected publications: JTK_CYCLE · CircaDB · CYCLOPS · MetaCycle

Circadian Medicine

Published human transcriptomics from the lab extended circadian biology into translational settings. This work showed that you can recover time of day from human data, inform physiology and pharmacology, and point the way to better treatments.

• Human circadian transcriptomics using CYCLOPS.
• Published resources connecting rhythmic gene expression to medicine.
• Conceptual and empirical work on chronotherapy and timed treatment.
• Time restricted feeding in bone marrow transplant.

Selected publications: Dosing time matters · Human circadian atlas

Human Genetics and Rare Disease

Through the Human Genetics Division at Cincinnati Children’s, the lab studies circadian and sleep phenotypes in rare genetic disease. In Smith-Kingsmore syndrome, work with Andrew Liu and clinical collaborators connected gain-of-function MTOR variants with altered mTOR activity, circadian rhythms, and sleep-wake behavior. Published work also includes a patient-derived mouse model of DLG4-related SHINE syndrome that reproduces molecular, neurological, and sleep phenotypes.

The DLG4 SHINE Foundation supports this work as a funding and community partner.

• Rare-disease sleep and circadian phenotyping in Human Genetics.
• Clinical and functional studies of MTOR variants in Smith-Kingsmore syndrome, including circadian and sleep-wake phenotypes.
• A patient-derived model connecting a SHINE syndrome variant with molecular, neurological, and sleep phenotypes.
• Translational connections between genetic diagnosis, mechanism, and time-dependent physiology.

Selected links: Human Genetics at Cincinnati Children’s · Smith-Kingsmore syndrome study · SHINE syndrome study · Smith-Kingsmore Syndrome Foundation · DLG4 SHINE Foundation