User:Alan Horsager
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Contact Info
Alan Horsager, Ph.D.
Eos Neuroscience, Inc.
Chief Science Officer
2100 3rd Street
3rd Floor
Los Angeles, CA 90057
Phone: 213-989-6730
Email: horsager(at)eosneuroscience.com
University of Southern California
Instructor in Research
Department of Ophthalmology
Institute for Genetic Medicine
2250 Alcazar Street
CSA 256
Los Angeles, CA 90089
Phone: 323-442-1978
Email: horsager(at)usc.edu
Education
Dr. Alan Horsager received his B.A. in Psychology from the University of Washington and his Ph.D. in Neuroscience at the University of Southern California, where he trained with Dr. Ione Fine. During his Ph.D. thesis, he used psychophysical and computational techniques to study the use of microelectronic retinal prostheses for treating blindness in human patients. He has over 10 years of industry experience including medical device and pharmaceutical clinical research, regulatory affairs, and clinical project management. His academic knowledge includes the study of human visual perception, computational modeling, retinal physiology, animal visual behavior, and molecular biology.
- 2009, Ph.D. Neuroscience, University of Southern California
- 1997, BA Psychology, University of Washington
Research Interests
Academic: University of Southern California
The primary focus of the Horsager Lab is to develop novel gene therapies for the treatment of blindness due to photoreceptor disease. Our research is motivated by the need for therapies that are both broadly applicable and allow for precise neuromodulation, thus restoring naturalistic visual processing independent of the underlying cause of retinal disease. In addition, we have two supporting lines of research that are more basic in nature: 1) understanding how gene regulatory networks are modulated in normal, diseased, and treated states, and using these data to develop synthetic molecular tools to target transgene expression to specific tissue types, and 2) understanding how circuit-specific neuromodulation is integrated within the retina and its subsequent impact on visual perception.
Optogenetic Approach to Restoring Sight. We are using a combination of gene therapy and optogenetic techniques to restore sight to mouse models of blindness, specifically the rd10 model. This involves the development of adeno-associated viral vectors that deliver promoters + genes that encode light-sensitive protein expression to specific subsets of retinal cells, thus enabling circuit-specific activation of the retina. We are currently working on a method that targets expression of channelrhodopsin-2, a gene encoding a light-sensitive cation channel obtained from the green algae Chlamydomonas reinhardtii, to the ON bipolar cells. Our recent paper, published in Molecular Therapy, describes how this approach could be used to treat retinitis pigmentosa and age-related macular degeneration in human patients.
Understanding regulatory networks within individual retinal cell types. The retina consists of dozens of different cell types, each performing a highly specific task. Ganglion cells, the cells that transmit the retinal signal to cortex, consist of more than 20 different subtypes, suggesting that over 20 different discrete types of information are being processed in the retina and sent, in parallel, to higher visual centers. Understanding the molecular profile, or transcriptome, is fundamental to understanding their function. Combined with computational analyses, this provides information about how best to genetically target transgene expression to these different subtypes of cells so that each individual subtype can be studied independently.
Computational modeling and physiological characterization of specific retinal circuits. Each retinal microcircuit parses and modulates the visual signal from photon capture in the photoreceptors (or other light-sensitive cell) through the ganglion cells. Looking at this from a biophysical perspective and incorporating the use of different light-sensitive proteins with cell specific expression targeting, is is possible to interrogate and understand how these different cell types integrate and modulate the signal? We are combining physiological and compuational approaches to study these questions.
Commercial: Eos Neuroscience, Inc.
I co-founded Eos Neuroscience, Inc. with Ed Boyden, Ph.D. (Assistant Professor at the Media Lab, MIT) and Ben Matteo (serial entrepreneur in San Fransisco) in November 2007. I serve as the Chief Science Officer and direct the overall scientific aims of the company. Eos is an NIH grant-funded start-up company incubating at the House Ear Institute, an affiliate of USC, in downtown Los Angeles. The company is developing a revolutionary optical control platform to treat chronic and intractable neuro-degenerative disorders. Eos achieved proof-of-concept in blindness, its first therapeutic area of development, by restoring functional vision to mice blind from a photoreceptor disease similar to retinitis pigmentosa (a progressive retinal disease in humans).
The platform technology uses a gene therapy to selectively sensitize remaining neurons of a degenerated neural circuit. We use a viral delivery tool (adeno-associated virus) to deliver a gene (e.g., channelrhodopsin-2) which encodes a light-sensitive opsin protein. This approach provides three fundamental breakthroughs over existing therapeutic technologies: 1) exceptionally high specificity with the ability to genetically-target stimulation to specific cell types, 2) enhanced resolution over implanted electrical devices, and 3) the ability to depolarize as well as hyperpolarize (e.g., halorhodopsin) neural tissue.
To accomplish this work, we have developed a set of world-class collaborations including experts in gene therapy, optogenetics, virology, gene regulation, immunology, preclinical development, and clinical disease management.
Publications
Peer Reviewed
1. De Balthasari, C., Patel, S., Roy, A., Freda, R., Greewald, S.H., Horsager, A., Mahadevappa, M., Yanai, D., McMahon, M.J., Humayun, M.S., Greenberg, R.J., Weiland, J.D., Fine, I. “Factors affecting perceptual thresholds in epiretinal prostheses.” Inv. Vis. Ophth. Sci. 2008 Jun;49(6):2303-14. [1]
2. Horsager, A., Greenwald, S.H., Weiland, J.D., Humayun, M.S., Greenberg, R.J., McMahon, M.J., Boynton, G.M., Fine, I. “Predicting visual sensitivity in retinal prosthesis patients”. Inv. Vis. Ophth. Sci. 2009 Apr;50(4):1483-91. [2]
3. Greenwald, S.H., Horsager, A., Humayun, M.S., Greenberg, R.J., McMahon, M.J., Fine, I. “Brightness as a function of current amplitude in human retinal stimulation”. Inv. Vis. Ophth. Sci. 2009 Nov;50(11):5017-25. [3]
4. Horsager, A., Greenberg, R.J., Fine, I. “Spatiotemporal interactions in retinal prosthesis patients”. Inv. Vis. Ophth. Sci. 2010 Feb;51(2):1223-33. [4]
5. Horsager, A., Boynton, G.M., Greenberg, R.J., Fine, I. “Temporal interactions during paired-electrode stimulation in retinal prosthesis patients”. Inv. Vis. Ophth. Sci. 2011 Feb 1;52(1):549-57. [5]
6. Doroudchi, M.M., Greenberg, K.P, Liu, J., Silka, K.A., Boyden, E.S., Lockridge, J.A., Arman, A.C., Janani, R., Boye, S.E., Boye, S.L., Gordon, G.M., Matteo, B.C., Sampath, A.P., Hauswirth, W.W., Horsager, A. “Virally-Delivered Channelrhodopsin-2 Safely and Effectively Restores Visual Function in Multiple Models of Blindness”. Mol. Ther. Apr. 19 2011. [6].
Book Chapters
1. Chader, G.J., Horsager, A., Weiland, J., Humayun, M.S. “Injury & Repair: Prostheses.” In Dartt, D.A., Besharse, J.C., Dana, R. (Eds.), Encyclopedia of the Eye (Volume 2, pp. 408-413). Oxford, Academic Press. [7]
2. Horsager, A. and Fine, I. “The perceptual effects of chronic retinal stimulation.” In Dagnelie, G. (Eds.), Visual Prosthetics: Physiology, Bioengineering, and Rehabilitation. Springer; 2011. pp. 271-300. [8]
