Lang Lab

The Circadian Clock, OPN3, OPN4 and OPN5

We investigate how intra- and extraocular light sensing pathways regulate development, homeostasis and disease.

The Lang lab logo incorporates symbols from Dr. Lang’s home continent of Australia. These symbols are reminder that a human lifetime represents a long journey under the influence of the sun and stars.

Our research focus

The Lang lab studies biological mechanisms that underpin development, homeostasis and disease. Historically, we have had a special interest in development of the visual system and in this context have identified mechanisms of embryonic induction and epithelial morphogenesis. The current passion of the Lang lab is an investigation of the intra- and extraocular light sensing pathways mediated by the opsin family members OPN3 (encephalopsin), OPN4 (melanopsin) and OPN5 (neuropsin). We have shown that within the eye OPN4 and OPN5 regulate light-dependent vascular development and that OPN5 light sensing determines myopia susceptibility. Unexpectedly, we have also found that OPN3 in adipocytes and OPN5 in the brain each mediate light sensing responses that regulate body temperature and energy homeostasis. Our ongoing work will continue to investigate these unusual light sensing pathways and relate their activities to human disease.

The vasculature for the fetal retina.

This image is of the hyaloid vessels, the vasculature for the fetal retina. The red labeled cells are macrophages, and the green the vascular endothelial cells.

Opsin 3 Expression in White Adipocytes.

The cells shown in this image are white adipocytes, an energy storage cell that is crucial for normal metabolism. The green labeling indicates that these cells express Opsin 3. Analysis described in Nayak et al., Cell Reports, 2020 shows that Opsin 3 is required for light sensing in white adipocytes.

Opsin 3 expression in Purkinje cells.

These folded neuroepithelia are within the cerebellum of the mouse brain. The green labeling indicates that Opsin 3 is expressed in Purkinje cells, a type of neuron involved in motor coordination and learning.

Opsin 3 expression in the mouse brain cortex.

In this image, an Opsin 3 expression reporter identifies pyramidal neurons of layer V in the mouse brain cortex.

Opsin 4 expression in the suprachiasmatic nucleus.

The suprachiasmatic nucleus – shown here as the bilateral, teardrop-shaped structures – have a crucial role in circadian clock function. The aqua and magenta labeling shows the axonal innervation of the suprachiasmatic nucleus by melanopsin (OPN4) expressing retinal ganglion cells.

The preoptic area of the hypothalamus.

The preoptic area of the hypothalamus has a central role in regulating body temperature and energy homeostasis. This brain nucleus expresses both Opsin 5 and the leptin receptor (Lepr). In this image, the position of Lepr expressing neurons within the preoptic area is color-coded.

OPN4 and OPN5 in retinal ganglion cells.

The retina of the eye has many different types of light sensing cells. In this image, retinal ganglion cells that express melanopsin (OPN4) are labeled in green and those that express neuropsin (OPN5) are shown in red. OPN4 cells are responsive to blue light and OPN5 cells to violet light.

Axon projections in the retina.

The dorsal lateral geniculate nucleus shown here is an information processing center for visual pathways in the mouse. This image shows axon projections from ganglion cells in the retina in green and magenta.

OPN5 and the mouse retina.

A ganglion cell from the mouse retina that expresses neuropsin (OPN5) and thus can detect violet light.

Meet the lab

Our lab embraces and promotes diversity, equity, and inclusion. We base our strengths in teamwork, and believe that the most efficient way to achieve goals is though the collective search and discussion of ideas and approaches.

CLICK HERE TO CONTACT US If YOU WANT TO LEARN MORE ABOUT NEW OPPORTUNITIES, OUR RESEARCH VISION, AND LABORATORY PHILOSOPHY.

Interested in a postdoctoral position? Send us an email describing your background and scientific interests, and why you are interested in our lab.

Are you a graduate student interested in the lab? Please contact us! Students from a range of backgrounds, including neuroscience, biology, chemistry and engineering are welcome.

Richard Lang, PH.D., Co-Director: The Science of Light Center

Professor, Co-Director - The Science of Light Center

Dr. Lang is Australian by birth and did his Bachelor of Science with Honors and PhD at the University of Melbourne and the Melbourne branch of the Ludwig Institute for Cancer Research. Following Postdoctoral training in the lab of Nobel Prize winner J Michael Bishop at the University of California San Francisco, Dr Lang took an Assistant Professorship at the Skirball Institute of New York University Medical Center. In 2001, Dr. Lang was recruited to Cincinnati Children’s Hospital to the Emma and Irving Goldman Scholar endowed chair, the position he currently occupies. Work in the Lang Lab has evolved from the study of myeloid cells through developmental biology to the investigation of intra- and extraocular light sensing pathways in development, homeostasis and disease. This work has broad implications for human physiology and informs the design of buildings, including daylighting strategies and artificial lighting systems.

Curriculum Vitae

Shruti Vemaraju, PhD

Research Associate

Jonathan Mercado Reyes, PhD

Research Fellow

Courtney Burger, PhD

Research Fellow

Mutahar Andrabi, PhD

Research Associate

Paul Speeg

Lab Operations

KHINE YIN MON MON, PhD

Research Fellow

Kat Castleberry, CCRP

Research Supervisor

Shane DSouza, PhD

Research Fellow

Publications

Selected Publications available with direct PDF download

Jiang, X., Pardue, M.T., Mori, K., Ikeda, S.I., Torii, H., D’Souza, S., Lang, R.A., Kurihara, T. and Tsubota, K., 2021. Violet light suppresses lens-induced myopia via neuropsin (OPN5) in mice. Proceedings of the National Academy of Sciences, 118(22), p.e2018840118.

Zhang, K.X., D’Souza, S., Upton, B.A., Kernodle, S., Vemaraju, S., Nayak, G., Gaitonde, K.D., Holt, A.L., Linne, C.D., Smith, A.N. and Petts, N.T., 2020. Violet-light suppression of thermogenesis by opsin 5 hypothalamic neurons. Nature, 585(7825), pp.420-425.

Rao, S., Chun, C., Fan, J., Kofron, J.M., Yang, M.B., Hegde, R.S., Ferrara, N., Copenhagen, D.R. and Lang, R.A., 2013. A direct and melanopsin-dependent fetal light response regulates mouse eye development. Nature, 494(7436), pp.243-246.

Buhr, E.D., Vemaraju, S., Diaz, N., Lang, R.A. and Van Gelder, R.N., 2019. Neuropsin (OPN5) mediates local light-dependent induction of circadian clock genes and circadian photoentrainment in exposed murine skin. Current Biology, 29(20), pp.3478-3487.

Nguyen, M.T.T., Vemaraju, S., Nayak, G., Odaka, Y., Buhr, E.D., Alonzo, N., Tran, U., Batie, M., Upton, B.A., Darvas, M. and Kozmik, Z., 2019. An opsin 5–dopamine pathway mediates light-dependent vascular development in the eye. Nature cell biology, 21(4), pp.420-429.

Nayak, G., Zhang, K.X., Vemaraju, S., Odaka, Y., Buhr, E.D., Holt-Jones, A., Kernodle, S., Smith, A.N., Upton, B.A., D’Souza, S. and Zhan, J.J., 2020. Adaptive thermogenesis in mice is enhanced by opsin 3-dependent adipocyte light sensing. Cell reports, 30(3), pp.672-686.

To contact the Lang Lab:

Cincinnati Children’s Hospital Medical Center

Division of Pediatric Ophthalmology

3333 Burnet Ave R2447

Cincinnati; State: Ohio, 45230

Useful links:

Cincinnati Children’s DEI strategic plan <Link>

Division of Pediatric Ophthalmology at CCHMC <Link>

Media:

Cincinnati Children’s Has Installed A Light That Mimics The Sun… <Link>

Cincinnati Children’s Is Licensing It’s Sunlight Technology To NASA Spinoff <Link>