Ali Deniz D. Güler


Primary Appointment

Associate Professor, Biology


  • BA, Bowdoin College
  • PhD, Biochemistry, Johns Hopkins School of Medicine

Research Disciplines


Research Interests

Circadian entrainment for the treatment of metabolic and neurodegenerative diseases

Research Description

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. Alzheimerâs and Parkinsonâs) 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 Alzheimerâs 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.

Personal Statement

My long-standing interest centers on how the central nervous system integrates both internal and external stimuli to generate a behavioral response. As a postdoctoral fellow in the laboratory of Dr. Samer Hattar (Johns Hopkins University), I identified the major pathway that carries environmental light information for non-image forming visual functions, including circadian photoentrainment and pupil constriction (Nature, 2008; PNAS, 2008; Nat. Neurosci. 2010). Next, in the laboratory of Dr. Richard Palmiter at University of Washington, I developed a transgenic model to modulate the activity of dopaminergic system and probe its role in a variety of behaviors including feeding (Nat. Commun., 2012; Cell Metab., 2015). In my own laboratory, we are uncovering how dopaminergic inputs to the circadian and energy balance circuits fine-tune physiological and behavioral responses (Curr. Bio., 2017 and 2020; eLife, 2020). To this end, we are developing and applying cutting-edge viral tracing strategies and in vivo neurotransmitter or electrophysiology measurement methodologies in awake and behaving mice. We perform these experiments in combination with optogenetic or chemogenetic actuators to classify specific cell groups or relevant neuronal connections (Curr. Bio., 2017 and 2020). Furthermore, we develop technologies to manipulate the behavioral responses predictably by activating the actuator proteins while the animals are freely behaving (Nat. Neurosci., 2016 and 2019).


  • Predoctoral Training in Neuroscience

Selected Publications

Wheeler M. A., Smith C. J., Ottolini M., Barker B. S., Purohit A. M., Grippo R. M., Gaykema R. P., Spano A. J., Beenhakker M. P., Kucenas S., Patel M. K., Deppmann C. D., Guler A. D., Genetically targeted magnetic control of the nervous system, 2020; Nat Neurosci. 19(5) 756-761. PMID: | PMCID: 26950006

Podyma B., Johnson D. A., Sipe L., Remcho T. P., Battin K., Liu Y., Yoon S. O., Deppmann C. D., Guler A. D., The p75 neurotrophin receptor in AgRP neurons is necessary for homeostatic feeding and food anticipation, 2020; Elife. 9() . PMID: | PMCID: 31995032

Grippo R. M., Tang Q., Zhang Q., Chadwick S. R., Gao Y., Altherr E. B., Sipe L., Purohit A. M., Purohit N. M., Sunkara M. D., Cios K. J., Sidikpramana M., Spano A. J., Campbell J. N., Steele A. D., Hirsh J., Deppmann C. D., Wu M., Scott M. M., Guler A. D., Dopamine Signaling in the Suprachiasmatic Nucleus Enables Weight Gain Associated with Hedonic Feeding, 2020; Curr Biol. 30(7) 1352-1355. PMID: | PMCID: 31902720

Grippo R. M., Purohit A. M., Zhang Q., Zweifel L. S., Guler A. D., Direct Midbrain Dopamine Input to the Suprachiasmatic Nucleus Accelerates Circadian Entrainment, 2017; Curr Biol. 27(16) 2465-2475 e3. PMID: | PMCID: PMC5568465

Pang Z, Sakamoto T, Tiwari V, Kim YS, Yang F, Dong X, Güler AD, Guan Y, Caterina MJ, Selective keratinocyte stimulation is sufficient to evoke nociception in mice., 2015; Pain. 156(4) 656-65. PMID: 25790456

Suli A, Guler AD, Raible DW, Kimelman D, A targeted gene expression system using the tryptophan repressor in zebrafish shows no silencing in subsequent generations., 2014; Development (Cambridge, England). 141(5) 1167-74. PMID: 24550120 | PMCID: PMC3929415

Soden ME, Jones GL, Sanford CA, Chung AS, Güler AD, Chavkin C, Luján R, Zweifel LS, Disruption of dopamine neuron activity pattern regulation through selective expression of a human KCNN3 mutation., 2013; Neuron. 80(4) 997-1009. PMID: 24206670 | PMCID: PMC3840077

Güler AD, Rainwater A, Parker JG, Jones GL, Argilli E, Arenkiel BR, Ehlers MD, Bonci A, Zweifel LS, Palmiter RD, Transient activation of specific neurons in mice by selective expression of the capsaicin receptor., 2012; Nature communications. 3() 746. PMID: 22434189 | PMCID: PMC3592340

Quintana A, Sanz E, Wang W, Storey GP, Güler AD, Wanat MJ, Roller BA, La Torre A, Amieux PS, McKnight GS, Bamford NS, Palmiter RD, Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors., 2012; Nature neuroscience. 15(11) 1547-55. PMID: 23064379 | PMCID: PMC3483418

Lall GS, Revell VL, Momiji H, Al Enezi J, Altimus CM, Güler AD, Aguilar C, Cameron MA, Allender S, Hankins MW, Lucas RJ, Distinct contributions of rod, cone, and melanopsin photoreceptors to encoding irradiance., 2010; Neuron. 66(3) 417-28. PMID: 20471354 | PMCID: PMC2875410

Altimus CM, Güler AD, Alam NM, Arman AC, Prusky GT, Sampath AP, Hattar S, Rod photoreceptors drive circadian photoentrainment across a wide range of light intensities., 2010; Nature neuroscience. 13(9) 1107-12. PMID: 20711184 | PMCID: PMC2928860

Chung MK, Güler AD, Caterina MJ, TRPV1 shows dynamic ionic selectivity during agonist stimulation., 2008; Nature neuroscience. 11(5) 555-64. PMID: 18391945

Güler AD, Ecker JL, Lall GS, Haq S, Altimus CM, Liao HW, Barnard AR, Cahill H, Badea TC, Zhao H, Hankins MW, Berson DM, Lucas RJ, Yau KW, Hattar S, Melanopsin cells are the principal conduits for rod-cone input to non-image-forming vision., 2008; Nature. 453(7191) 102-5. PMID: 18432195 | PMCID: PMC2871301

Altimus CM, Güler AD, Villa KL, McNeill DS, Legates TA, Hattar S, Rods-cones and melanopsin detect light and dark to modulate sleep independent of image formation., 2008; Proceedings of the National Academy of Sciences of the United States of America. 105(50) 19998-20003. PMID: 19060203 | PMCID: PMC2596746

Sidhaye VK, Güler AD, Schweitzer KS, D'Alessio F, Caterina MJ, King LS, Transient receptor potential vanilloid 4 regulates aquaporin-5 abundance under hypotonic conditions., 2006; Proceedings of the National Academy of Sciences of the United States of America. 103(12) 4747-52. PMID: 16537379 | PMCID: PMC1450241

Chung MK, Güler AD, Caterina MJ, Biphasic currents evoked by chemical or thermal activation of the heat-gated ion channel, TRPV3., 2005; The Journal of biological chemistry. 280(16) 15928-41. PMID: 15722340

Güler AD, Lee H, Iida T, Shimizu I, Tominaga M, Caterina M, Heat-evoked activation of the ion channel, TRPV4., 2002; The Journal of neuroscience : the official journal of the Society for Neuroscience. 22(15) 6408-14. PMID: 12151520

Warthen D. M., Lambeth P. S., Ottolini M., Shi Y., Barker B. S., Gaykema R. P., Newmyer B. A., Joy-Gaba J., Ohmura Y., Perez-Reyes E., Guler A. D., Patel M. K., Scott M. M., Activation of Pyramidal Neurons in Mouse Medial Prefrontal Cortex Enhances Food-Seeking Behavior While Reducing Impulsivity in the Absence of an Effect on Food Intake, ; Front Behav Neurosci. 10() 63. PMID:

Grippo R. M., Guler A. D., Dopamine Signaling in Circadian Photoentrainment: Consequences of Desynchrony, ; Yale J Biol Med. 92(2) 271-281. PMID:

Walker M. T., Rupp A., Elsaesser R., Guler A. D., Sheng W., Weng S., Berson D. M., Hattar S., Montell C., RdgB2 is required for dim-light input into intrinsically photosensitive retinal ganglion cells, ; Mol Biol Cell. 26(20) 3671-8. PMID:

Denis R. G. P., Joly-Amado A., Webber E., Langlet F., Schaeffer M., Padilla S. L., Cansell C., Dehouck B., Castel J., Delbes A. S., Martinez S., Lacombe A., Rouch C., Kassis N., Fehrentz J. A., Martinez J., Verdie P., Hnasko T. S., Palmiter R. D., Krashes M. J., Guler A. D., Magnan C., Luquet S., Palatability Can Drive Feeding Independent of AgRP Neurons, ; Cell Metab. 25(4) 975. PMID: | PMCID: PMID: 26278050