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Neuropeptide Y (NPY) can alter circadian rhythms by directly resetting rhythms, or by blocking the resetting effects of light. Our current research uses several approaches to better understand these actions of NPY.
We can examine the behavioral and physiological consequences of loss of NPY or of a particular NPY receptor. Some of this work is supported by a grant from the National Science Foundation (NSF RUI 0234203).
Pharmacological tools, such as blockers of specific NPY receptors, allow us to test hypotheses about the role of NPY at particular circadian phases or in interaction with other drugs or with light. We are collaborating with Pfizer, Inc. in some of these studies. We have discovered that combining NPY and serotonergic antagonists can greatly increase the action of light on the circadian clock (Lall and Harrington, 2006). We are now continuing this research in work supported by the National Institutes of Health.
Here is a fantastic paper for background on circadian clock entrainment.
We are beginning studies to address the link between disruption of circadian rhythms and cancer. Our interest in this question comes from epidemiological studies that suggest a link between occupations that involve shift work or frequent jet lag and an increased incidence of cancer. Other studies indicate that patients with metastatic disease show better outcome if their circadian rhythms are more robust.
How might disruption of circadian rhythms alter the multitude of pathways that lead to cancer? We conducted a study to determine if jet lag reduces the ability to respond to genetic damage. Our initial results were presented at the meeting of the Society for Research on Biological Rhythms in 2004.
Mary spent her sabbatical year 2005-6 in Toronto, working with Dr. Georg Bjarnason at Sunnybrook Hospital. Dr. Bjarnason is an oncologist and an expert on the topic of the impact of circadian clock disruption on cancer. Our research is now funded by the National Cancer Institute of NIH as we test if cytokines act on the circadian clock to cause cancer-related fatigue.
We are studying circadian rhythms in the SCN, liver, lung, testes, esophagus, spleen, mammary gland, and thymus. The phase and period varies in tissues throughout the body, but the SCN phase-leads most body organs.
We have collaborated with Dr. Chiaki Fukuhara to measure effects of altered kinase activation on circadian clock period in multiple tissues. In collaboration with Dr. Paola Yannielli we have measured effects of ghrelin, a peptide secreted by a hungry stomach, on circadian clock tissue. We are using this technique in studies of jet lag, seasonal changes,and aftereffects from entrainment to exotic T cycles. This work was funded by NSF 0423200, Smith College STRIDE, HHMI, and the Dean for Academic Development.
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