Current research in my lab focuses on the integrative analysis of circadian systems in mammals using rodent models. Using reporter gene tools and a variety of methods for measuring organ function and behavior, our goal is to develop an understanding of whole-organism rhythmicity and how it relates to both healthy and abnormal function.

Circadian rhythmicity (the ability of living systems to undertake periodic functions in cycles of 24 hours) is a fundamental property of life. Circadian rhythms are present in all organisms from bacteria to mammals and they are all based upon autoregulatory feedback loops of “clock” gene expression.

There are currently two specific projects in the lab:

The first aims to study how aging is involved in the ability of the circadian system to cope with manipulations of the environmental signals. We, together with Gene Block, Mike Menaker and colleagues at the University of Virginia, have discovered that aged mice submitted to repeat shifts of the light schedule (similar to a weekly transmeridian travel or rotating shiftwork) die sooner than mice kept under normal light-dark cycles. We are investigating the mechanisms that accelerate death, and future experiments will address possible countermeasures.

Manipulations of the circadian system can either enhance or inhibit cancer initiation and progression. The second main project in my lab addresses how manipulation of circadian rhythms impacts the development and progression of malignancies. Our early studies indicate that rat hepatocellular carcinoma, or liver cancer, expresses an endogenous circadian rhythm, and this rhythm is different from the rhythms measured from adjacent healthy host tissue. Our current studies in mice are focused on lung cancer and prostate cancer. In both of these systems we are integrating luciferase reporters for circadian clock genes into tumors in order to monitor in real time the circadian ‘behavior’ of the tumors during manipulations of the host circadian rhythms. We are trying to determine how manipulations such as chronic jet lag, constant light, and restricted feeding alter tumor growth, in the hopes that this information can be used to prevent, or better treat cancers in humans.