Ali D. Güler
- B.A., Bowdoin College, 1999
- Ph.D., Johns Hopkins School of Medicine, 2006
- Postdoctoral, Johns Hopkins University, 2006-2008
- Postdoctoral, University of Washington, 2008-2013
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. Alzheimer’s and Parkinson’s) 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.
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. We showed that this pathway accelerates entrainment and drives palatable food consumption outside of mealtimes. Now, we are leveraging our expertise in disentangling circadian entrainment neurocircuitry to determine whether strengthening circadian rhythmicity ameliorates symptoms of metabolic disorders or Alzheimer’s 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.
- Podyma B, Johnson DA, Sipe L, Remcho TP, Battin K, Liu Y, Yoon SO, Deppmann CD, Güler AD. (2020) The p75 neurotrophin receptor in AgRP neurons is necessary for homeostatic feeding and food anticipation. Elife. 9:e52623.
- Grippo RM, Tang Q, Zhang Q, Chadwick SR, Gao Y, Altherr EB, Sipe L, Purohit AM, Purohit NM, Sunkara MD, Cios KJ, Sidikpramana M, Spano AJ, Campbell JN, Steele AD, Hirsh J, Deppmann CD, Wu M, Scott MM, Güler AD. (2020) Dopamine signaling in the suprachiasmatic nucleus enables weight gain associated with hedonic feeding. Curr Biol, Jan 20; 30,196-208.
- Grippo RM, Purohit AM, Zhang Q, Zweifel LS, Güler AD. (2017) Direct Midbrain Dopamine Input to the Suprachiasmatic Nucleus Accelerates Circadian Entrainment. Curr Biol, Aug 21; 27, 2465-2475.
- Wheeler MA, Smith CJ, Ottolini M, Barker BS, Purohit AM, Grippo RM, Gaykema RP, Spano AJ, Beenhakker MP, Kucenas S, Patel MK, Deppmann CD, Güler AD. (2016) Genetically targeted magnetic control of the nervous system. Nat Neurosci. Mar 7.
- Güler AD, Rainwater A, Parker J, Jones GL, Argilli E, Arenkiel BR, Ehlers MD, Bonci A, Zweifel LS, Palmiter RD. (2012) Transient activation of specific neurons in mice by selective expression of the capsaicin receptor. Nat Commun. Mar. 3:746.
- Güler AD, Ecker JL, Lall GS, Haq S, Altimus CM, Liao H-W, Barnard AR, Cahill H, Badea TC, Hankins MW, Berson DM, Lucas RJ, Yau K-W, Hattar S. (2008) Melanopsin cells are the principal conduits for rod–cone input to non-image-forming vision. Nature. May 1;453(7191):102-
For a comprehensive list of Dr. Güler's publications, please click here.