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������ý Researchers Receive $1.3 Million NIH Grant for Stem Cell Research

Co-investigator Lisa Ann Brennen, Ph.D., research associate professor; and Marc Kantorow, Ph.D., principal investigator, assistant dean for graduate studies and a professor of biomedical science, ������ý's Schmidt College of Medicine, in the Kantorow Laboratory. (Photo by Alex Dolce)

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Researchers from ������ý’s hope to conquer a major limitation in the ability for scientists to engineer tissues for regenerative therapies for age-related and degenerative diseases. They recently received a $1.3 million grant from the National Eye Institute of the National Institutes of Health (NIH) for a project that will identify novel mechanisms for how immature eye cells activate genes to become mature visual cells. The five-year (total grant $2.7 million), multiple principal investigator grant will be conducted in collaboration with researchers from in Pennsylvania.

“This grant from the National Institutes of Health, National Eye Institute will enable us to identify the gene regulation pathways activated to program immature stem-like cells of the eye lens to attain their mature form and transparent function,” said , Ph.D., principal investigator, assistant dean for graduate studies and a professor of biomedical science in ������ý’s Schmidt College of Medicine.

Kantorow and co-investigator , Ph.D., research associate professor in ������ý’s Schmidt College of Medicine, have discovered that specific changes in DNA conformation during tissue development regulate the activation of genes needed to make a functional eye lens through activation of novel DNA binding proteins called transcription factors.

“With this grant, we plan to explore the genetic and cellular mechanisms controlling developmental DNA conformational changes and will identify the transcription factors needed for eye lens formation,” said Brennan.

Since DNA conformational changes activates the function of genes required for the development of a wide-array of tissues and organs, the outcome of this research will provide a basis for the development of regenerative therapies for diseases from retinal degeneration through heart disease. Because disruption of eye lens gene activation causes cataract formation, the outcome of these studies has implications for preventing cataract, which is the leading cause of world blindness.

“The promise of regenerative medicine relies on the ability of scientists to engineer transplantable tissues that can replace diseased or damaged tissues,” said , Ph.D., senior associate dean for research and chair of the in ������ý’s Schmidt College of Medicine. “This significant NIH funding will enable Dr. Kantorow and his team to gain a deeper understanding into complex cellular remodeling events. The information they gain from these studies will be applicable toward the development of novel tissue engineering strategies to develop ocular and other cells for replacement of damaged and diseased tissues.”

According to the World Health Organization (WHO), cataract is responsible for 51 percent of world blindness. Although cataracts can be surgically removed, in many countries barriers exist that prevent patients to access surgery. Cataract remains the leading cause of blindness. In the United States, an estimated 20.5 million (17.2 percent) Americans aged 40 years and older have cataract in one or both eyes, and 6.1 million (5.1 percent) have had their lens removed operatively. Cataract is clouding of the eye lens, which prevents clear vision. Although most cases of cataract are related to the aging process, occasionally children can be born with the condition, or a cataract may develop after eye injuries, inflammation, and some other eye diseases.

The Kantorow Laboratory focuses on understanding mechanisms of ocular development and disease. Specifically, his team focuses on the eye lens and the retina as models for understanding cell differentiation, cell function and disease mechanisms. Their work ranges from analysis of the functions of genes identified to cause ocular disease when mutated, to the direct effects of UV-light and other agents associated with the development of ocular disease on mitochondrial and other cellular functions.

In addition to understanding how the functions of ocular cells are altered in disease states, the Kantorow Laboratory team examines how manipulation of key cell systems can be applied to treat and/or prevent ocular diseases including age-related cataract formation and macular degeneration that are the leading causes of visual disability. Knowledge gained from these studies to engineer cell systems and cells that can be transplanted into cells or tissues could restore the functions of damaged organs.

The Kantorow Laboratory and research program have been continually funded by the NIH’s National Eye Institute for almost two decades.

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