Johnson, Brian - Date Last Updated: 01/11/2012

Brian Johnson - Email
PhD Candidate - Started 2007
Westland, MI
Lab of Christopher Bradfield, PhD

Undergraduate Work
Michigan Technological University (2001-2004)
Bachelors of Science - Biology (2004)

Research as of Fall 2009
The Bradfield lab works on the Per-Arnt-Sim (PAS) family of nuclear transcription factors including Ahr, Arnt, Mop3 (Bmal1) and the Hif’s. This family modulates diverse cellular processes such as chemical sensing, circadian rhythms and response to hypoxia. My current project is involved with investigating the role of the circadian clock in cellular metabolism.

At the cellular level, virtually every cell type in the body maintains its own twenty four hour molecular clock. These individual cell clocks are organized or “set” by a central clock in the SCN at the base of the hypothalamus in the brain. The central clock receives neural input from specialized cells in the retina, entraining it to light/dark rhythms. The SCN then coordinates neural and hormonal signals to all other cells in the body generating rest/activity cycles of twenty four hours. In the liver, this causes daily oscillations in the expression and activity of many enzymes important in Phase I and II metabolism as well as uptake and transport. The clock and therefore the time of day have a significant impact on the disposition and toxicity of endogenous and exogenous compounds in the body.

The idea that daily oscillations in metabolism are important to toxicology is supported by other observations. Primarily, it has been shown that a patient’s response to chemotherapy is strongly correlated with time of administration of the drug, although it has been difficult to show if the clock itself or other factors such as eating patterns are responsible. Also, epidemiologic studies show that disrupting an individual’s daily rhythm by rotating shift work affects breast and colon cancer risk. Therefore, a better understanding of the interactions between the clock and metabolism has reaching implications.

My current research involves using microarray technology to study the transcriptional changes in the liver upon deletion of the hepatocyte clock. We have found that while 10% of the genes in the liver cycle with significant 24 hour rhythm, a much larger percentage are disrupted upon deletion of the hepatocyte clock. Further, we have found significant changes in the disposition of Acetaminophen upon disruption of the hepatocyte clock, even under similar activity/eating patterns. These results implicate the hepatocyte clock directly, as opposed to indirectly through other patterns, in modulation of these toxicity patterns. Thus the hepatocyte clock itself could be a target for modulating an individual’s response to drugs, especially chemotherapies.

Interests
Volleyball, hiking/geo-caching, skiing, biking, camping, softball, boating, classic cars hunting….. basically anything that gets me outside. When indoors, I like playing board games or cards with my girlfriend (Jenny) and friends, hanging out with our 20-somethings Bible study group, or talking to friends and family back home in Michigan.

Graduate Seminars Given

01/26/12
Elucidating the Role of the Aryl Hydrocarbon Receptor in Normal Vascular Development

01/27/11
Elucidation of the Endogenous Ahr Signaling Pathway(s) in Vascular Endothelia

01/28/10
Dissecting the Cell Autonomous Circadian Clock: Integration of microarray datasets to test and predict mechanisms of circadian oscillations

Date Last Updated: 01/11/2012 webteam@med.wisc.edu