Kyushu University · Medicine
Professor Shigehiro Ohdo's research lab focuses on the molecular mechanisms linking circadian rhythms to drug metabolism, xenobiotic transport, and chronopharmacology. The lab investigates how clock-controlled transcription factors such as DBP and E4BP4 regulate the rhythmic expression of drug-metabolizing enzymes and transporters like CYP3A4 and ABCG2. Key research directions include understanding the circadian regulation of drug response, the role of nuclear receptors (e.g., PPARα) in metabolic enzyme oscillations, and the impact of biological timing on therapeutic efficacy and toxicity. The lab also explores the translational implications of these rhythms for optimizing drug dosing schedules in conditions like neuropathic pain and cancer chemotherapy.
Figures are computed from collected data and may differ slightly.
Results from this study suggest that DBP and E4BP4 might consist of a reciprocating mechanism in which DBP activates the transcription of the CYP3A4 gene during the time of day when DBP is abundant, and E4BP4 suppresses the transcription at other times of day. Our current findings provide a molecular link between the circadian clock and the xenobiotic metabolism.
The mammalians circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN) and influences a multitude of biological processes, including the sleep-wake rhythm. Clock genes are the genes that control the circadian rhythms in physiology and behavior. The effectiveness and toxicity of many drugs vary depending on dosing time associated with 24 hr rhythms of biochemical, physiological and behavioral processes under the control of circadian clock. Such chronopharmacological phenomena are i
These findings suggest that the dosing time-dependent difference in the anti-allodynic effects of gabapentin is attributable to the circadian oscillation of α2δ-1 subunit expression in the DRG and indicate that the optimizing its dosing schedule helps to achieve rational pharmacotherapy for neuropathic pain.
We report two sisters with mental retardation, congenital heart disease, blepharophimosis, blepharoptosis, and hypoplastic teeth. A female paternal cousin has the same anomalies, but without congenital heart disease. The chromosomes of these patients are normal and the parents are non-consanguineous.
Xanthine oxidase (XOD), also known as xanthine dehydrogenase, is a rate-limiting enzyme in purine nucleotide degradation, which produces uric acid. Uric acid concentrations in the blood and liver exhibit circadian oscillations in both humans and rodents; however, the underlying mechanisms remain unclear. Here, we demonstrate that XOD expression and enzymatic activity exhibit circadian oscillations in the mouse liver. We found that the orphan nuclear receptor peroxisome proliferator-activated rec
ABCG2, encoding breast cancer resistance protein (BCRP), is a member of the ATP-binding cassette transporter family and is often associated with cancer chemotherapeutic resistance. BCRP is also expressed in a variety of normal cells and acts as a xenobiotic efflux transporter. Because intestinal BCRP limits systemic exposure to xenobiotics, alterations in the function and expression of this transporter could account for part of the variation in oral drug absorption. In this study, we show that A
Iron is an important biological catalyst and is critical for DNA synthesis during cell proliferation. Cellular iron uptake is enhanced in tumor cells to support increased DNA synthesis. Circadian variations in DNA synthesis and proliferation have been identified in tumor cells, but their relationship with intracellular iron levels is unclear. In this study, we identified a 24-h rhythm in iron regulatory protein 2 (IRP2) levels in colon-26 tumors implanted in mice. Our findings suggest that IRP2
Cardiac toxicity caused by doxorubicin (adriamycin) is a serious dose-limiting factor in the clinical situation. However, the influence of doxorubicin dosing time has not been clarified from the viewpoints of cardiotoxic development and its mechanism. In this study, we have investigated the dosing time dependency of doxorubicin-induced cardiotoxicity and bone marrow toxicity after repeated administration of doxorubicin in rats. When doxorubicin (5 mg kg(-1), i.p.) was administered every seven da
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