Güler, Ali Deniz D.
Associate Professor, Biology
- BA, Bowdoin College
- PhD, Biochemistry, Johns Hopkins School of Medicine
Molecular Biology, Neuroscience
Circadian entrainment for the treatment of metabolic and neurodegenerative diseases
Biological processes ranging from gene transcription to behavior oscillate and are synchronized to the 24-hour day/night cycle. Mammalian circadian rhythms, orchestrated by the hypothalamic suprachiasmatic nucleus (SCN) allow appropriately timed physiological and behavioral responses to daily recurring external cues (i.e. sunrise or timed meal availability). The resulting synchrony of physiology to the astronomical day maximizes metabolic efficiency and good health. However, many of the stresses of modern society (i.e. artificial lighting and omnipresence of food) weaken and desynchronize circadian rhythms. This in turn increases the prevalence of many pathologies including metabolic disorders (i.e. obesity, type 2 diabetes and cardiovascular diseases), neurodegenerative diseases (i.e. Alzheimers and Parkinsons) and many types of cancer. The aim of my laboratory is to determine how circadian rhythms are synchronized (entrained) to external cues and how desynchronization impacts health. Although the neuronal pathways of light-driven entrainment are well-established, how other external cues, such as food availability, social interactions or exercise, influence the workings of the SCN remains unknown. In a recent breakthrough, we identified a neuronal connection between midbrain dopaminergic neurons that are activated in response to salient rewarding events and SCN neurons that express the dopamine receptor. We showed that this pathway accelerates entrainment and drives palatable food consumption outside of mealtimes. In parallel, we identified a novel molecular player that is necessary for anticipation of time-restricted food access. Now, we are leveraging our expertise in disentangling circadian entrainment neurocircuitry to determine whether strengthening circadian rhythmicity ameliorates symptoms of metabolic disorders or Alzheimers disease. Our work is aimed at understanding the relationship between entrainment cues, physiology and behavior while providing tangible strategies against the adverse consequences of circadian misalignment.