Ali D. Guler

Education

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

Contact

Research Interest(s)

Behavior and epigenetics; Building and wiring the brain; Neurodevelopmental and neuropsychiatric disorders; Biological timing: circadian rhythms.

Research Description

Our research focuses on understanding how mammalian central nervous system integrates and processes environmental and peripheral signals for proper behavioral responses. Feeding, sleeping or sex require opportune times that combine information gathered by multiple brain regions and are differentially gated. How does the brain weigh myriad stimuli to shape a behavioral output? To determine how such a large neural network functions, it is essential to influence the activity of a subpopulation of neurons and observe both physiological and behavioral responses simultaneously. Using genetic tools that allow precise control of neural activity in combination with in vivo electrophysiology and behavioral assays, we are discovering circuits that regulate homeostatic behaviors. Currently, we are focusing our efforts on understanding the role of genetically-defined populations of neurons within hypothalamus and midbrain during behaviors associated with feeding or thermoregulation in mice.

Since innovating and improving tools to manipulate molecular, biochemical or electrical characteristics of specific cell types is crucial in leading new discoveries, we are also seeking opportunities to create techniques to alter the biology of a single protein or a network of cells in a predictable manner. To this end, we are generating novel combination of viral and genomic constructs that allow manipulation of both endogenous and exogenous genes in anatomical, genetic and/or temporal space.

Selected Publications

  • Altimus C. M., Guler A. D., Alam N. M., Arman A. C., Prusky G. T., Sampath A. P., Hattar S.. Rod photoreceptors drive circadian photoentrainment across a wide range of light intensities Nat Neurosci. 13(9): 1107-12.
  • Altimus C. M., Guler A. D., Villa K. L., McNeill D. S., Legates T. A., Hattar S.. Rods-cones and melanopsin detect light and dark to modulate sleep independent of image formation Proc Natl Acad Sci U S A. 105(50): 19998-20003.
  • Chung M. K., Guler A. D., Caterina M. J.. Biphasic currents evoked by chemical or thermal activation of the heat-gated ion channel, TRPV3 J Biol Chem. 280(16): 15928-41.
  • Chung M. K., Guler A. D., Caterina M. J.. TRPV1 shows dynamic ionic selectivity during agonist stimulation Nat Neurosci. 11(5): 555-64.
  • Guler A. D., Altimus C. M., Ecker J. L., Hattar S.. Multiple photoreceptors contribute to nonimage-forming visual functions predominantly through melanopsin-containing retinal ganglion cells Cold Spring Harb Symp Quant Biol. 72 509-15.
  • Guler A. D., Ecker J. L., Lall G. S., Haq S., Altimus C. M., Liao H. W., Barnard A. R., Cahill H., Badea T. C., Zhao H., Hankins M. W., Berson D. M., Lucas R. J., Yau K. W., Hattar S.. Melanopsin cells are the principal conduits for rod-cone input to non-image-forming vision Nature. 453(7191): 102-5.
  • Guler A. D., Lee H., Iida T., Shimizu I., Tominaga M., Caterina M.. Heat-evoked activation of the ion channel, TRPV4 J Neurosci. 22(15): 6408-14.
  • Guler A. D., Rainwater A., Parker J. G., Jones G. L., Argilli E., Arenkiel B. R., Ehlers M. D., Bonci A., Zweifel L. S., Palmiter R. D.. Transient activation of specific neurons in mice by selective expression of the capsaicin receptor Nat Commun. 3 746.
  • Lall G. S., Revell V. L., Momiji H., Al Enezi J., Altimus C. M., Guler A. D., Aguilar C., Cameron M. A., Allender S., Hankins M. W., Lucas R. J.. Distinct contributions of rod, cone, and melanopsin photoreceptors to encoding irradiance Neuron. 66(3): 417-28.
  • Quintana A., Sanz E., Wang W., Storey G. P., Guler A. D., Wanat M. J., Roller B. A., La Torre A., Amieux P. S., McKnight G. S., Bamford N. S., Palmiter R. D.. Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors Nat Neurosci. 15(11): 1547-55.
  • Sidhaye V. K., Guler A. D., Schweitzer K. S., D'Alessio F., Caterina M. J., King L. S.. Transient receptor potential vanilloid 4 regulates aquaporin-5 abundance under hypotonic conditions Proc Natl Acad Sci U S A. 103(12): 4747-52.
  • Soden M. E., Jones G. L., Sanford C. A., Chung A. S., Guler A. D., Chavkin C., Lujan R., Zweifel L. S.. Disruption of dopamine neuron activity pattern regulation through selective expression of a human KCNN3 mutation Neuron. 80(4): 997-1009.
  • Suli A., Guler A. D., Raible D. W., Kimelman D.. A targeted gene expression system using the tryptophan repressor in zebrafish shows no silencing in subsequent generations Development. 141(5): 1167-74.
  • Xu H., Hirosumi J., Uysal K. T., Guler A. D., Hotamisligil G. S.. Exclusive action of transmembrane TNF alpha in adipose tissue leads to reduced adipose mass and local but not systemic insulin resistance Endocrinology. 143(4): 1502-11.