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NIH Grants $12.5M for Optogenetics, Imaging, Tumor Detection
Oct 2011
PHILADELPHIA, Oct. 6, 2011 — Three labs at the University of Pennsylvania have received $12.5 million from the National Institutes of Health (NIH) to pursue light-driven ideas expected to advance medical research.

These awards are granted under the NIH’s Pioneer, New Innovator and Transformative Research Projects awards as part of the organization’s $143.8 million national grant program.

Researchers at the University of Pennsylvania have received a grant to explore optogenetic techniques to restore light sensitivity to afflicted retinas. (Image: W. Tang, Bennett laboratory, Perelman School of Medicine)

The key investigators on the Pioneer Award are Jean Bennett, Luk Vandenberghe and Albert M. Maguire of the university-affiliated F.M. Kirby Center for Molecular Ophthalmology in the Scheie Eye Institute of the Perelman School of Medicine. The scientists have been awarded $4 million to use gene therapy to treat inherited forms of blindness, which can be caused by mutations in any of hundreds of different genes. The grant spans the next five years.

The three researchers plan to develop a small number of therapeutics that could restore vision to millions of patients who are blind due to a diverse set of retinal disorders. They propose resensitizing the blind eye using optogenetic techniques in which light-sensitive molecules are delivered to any remaining retinal cells. Preclinical studies in blind animals have demonstrated that this strategy is effective, and a new study would test the safety and efficacy of this approach in blind patients in the clinic.

The results from this project could lead to a significant improvement in the quality of life for millions of individuals and could also pave the way for development of novel gene therapy approaches to the treatment of other devastating sensory diseases.

Individual mRNA molecules (purple) come from a chromosome (blue) within a cell's nucleus (yellow). (Image: M. Levesque, Raj laboratory, Perelman School of Medicine)

Arjun Raj, assistant professor of bioengineering in the School of Engineering and Applied Science, received the New Innovator Award, worth $1.5 million over five years. Raj’s research involves the development and application of new microscopic imaging tools to reveal how the physical organization of the genetic code determines the manner in which the cell reads the code itself. The development of these methods will establish a "nuclear GPS" that should permit researchers to directly visualize genetic organization in single cells. An understanding of this organization will be important for discovering how defects in translating the genetic code contribute to diseases such as cancer.

The integrated multichannel imaging system is for intraoperative cancer detection and image-guided surgery. (Image: S. Singhal, Perelman School of Medicine)

A $7 million, five-year Transformative Research Project Award was given to a team of investigators from the Perelman School of Medicine and from Emory University and Georgia Institute of Technology, both in Atlanta. The researchers include Sunil Singhal, the director of the Thoracic Surgery Research Laboratory at the University of Pennsylvania.

If a tumor is more visible and easier to distinguish from surrounding tissues, surgeons are more likely to be able to remove it completely. At present, a significant number of patients who undergo surgery leave the operating room without total removal of the tumor. To address the problem, Singhal and his colleagues developed fluorescent nanoparticle probes that target cancer cells. Their main goals are to help surgeons distinguish tumor boundaries, identify diseased lymph nodes and determine whether a tumor has been completely removed.

The grant includes plans for tests of the nanoparticles in animal models and a clinical trial for patients with lung cancer. The proposed technologies could be broadly applicable to many types of solid tumors.

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The inability to perceive visual images (visible radiant energy). In human beings, blindness is defined as a visual acuity of less than one-tenth normal vision.
A discipline that combines optics and genetics to enable the use of light to stimulate and control cells in living tissue, typically neurons, which have been genetically modified to respond to light. Only the cells that have been modified to include light-sensitive proteins will be under control of the light. The ability to selectively target cells gives researchers precise control. Using light to control the excitation, inhibition and signaling pathways of specific cells or groups of...
Albert M. MaguireAmericasArjun RajBiophotonicsblindnessCancer CellsEmory UniversityF.M. Kirby Center for Molecular Ophthalmologyfluorescent nanoparticlesgene therapyGeorgiaGeorgia TechimagingJean BennettLuk Vandenberghemedical researchmicroscopy techniquesNational Institutes of HealthNew Innovator AwardsNIH grantsoptogeneticsPennsylvaniaPerelman School of MedicinePioneer AwardsResearch & Technologyretinal disordersSensors & DetectorsSunil SinghalTransformative Research Projects awardstumor boundariesUniversity of Pennsylvania

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