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Broad Institute earns grant to support pathbreaking diabetes study
Date:7/21/2008

Researchers at the Broad Institute of Harvard and MIT have received a grant to support novel, integrative research aimed at finding ways to encourage the human body to replenish the cells that are missing in type 1 diabetes. Awarded by the Juvenile Diabetes Research Foundation (JDRF), the $3M grant will fund work that knits together two interdisciplinary fields, genome biology and chemical biology, to address a fundamental question in human biology: can existing cells be coaxed to regenerate ones that are lost or damaged by disease?

"This grant will enable us to understand the inherent potential of human cells and how it might be harnessed in the future to improve health," said Stuart Schreiber, the grant's principal investigator and director of the Chemical Biology Program at the Broad Institute. "Our focus is on type 1 diabetes, a disease that typically surfaces in childhood and requires lifelong treatment, though our approach holds promise for practically any disease involving a cellular deficiency."

Diabetes stems from an inability to control the levels of glucose in the blood via a regulatory hormone called insulin. Type 1 diabetes is an autoimmune disease in which a person's pancreas stops producing insulin. The disease usually strikes in childhood, adolescence, or young adulthood, but lasts a lifetime. Patients with type 1 diabetes require lifelong insulin therapy, delivered through injections or a small, credit card-sized pump.

Yet that constant need for treatment might be lessened or perhaps eliminated altogether if the missing cells could be safely replaced. For example, surviving beta cells, while rare in type 1 patients, might be induced to multiply, creating enough copies of themselves to restore insulin supply. Or, perhaps other types of pancreatic cells could be redirected to become beta cells, a process known in scientific parlance as cellular reprogramming.

"From our initial proof-of-concept work, we know that human pancreatic tissue can be isolated and grown in the laboratory, and that in this environment, it maintains its normal physiology," said Bridget Wagner, a group leader in pancreatic cell biology and metabolic disease at the Broad Institute who is helping to lead the JDRF-funded research. "Now, the critical question is, can new beta cells be created from this tissue?"

The two-year grant from the JDRF will support the research needed to answer that question. A mainstay of the future work will involve the use of a vast chemical biology toolkit diverse collections of chemicals known as "small molecules", both for their molecular structure and their propensity to influence cells and cell behavior. "High-throughput methods enable us to analyze hundreds if not thousands of small molecules at once," said Aly Shamji, associate director of the Broad Institute's Chemical Biology Program. "The dramatic increase in throughput across a variety of scientific technologies is really transforming the kinds of problems we can tackle."

Pairing these advanced chemical tools with powerful genomic tools, which read cells' genetic information to help determine their identities, will enable the researchers to search for small molecules that promote beta cell growth and development. If successful, such discoveries would highlight the regenerative capacity of human cells, paving the way for future investigations of the approach as not only a potential treatment for diabetes, but also for a myriad of diseases that result from the degeneration of critical cell types.

"This is indeed an ambitious project," said Schreiber, who is also a professor at Harvard University and a Howard Hughes Medical Institute investigator. "Part of what makes it feasible, though, is drawing together the resources and expertise of two scientific fields into the new discipline of genomic medicine. We hope the visionary support of JDRF for this unique approach will enable us to accelerate progress in finding robust therapies for type 1 diabetes and perhaps other diseases as well."


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Contact: Nicole Davis
ndavis@broad.mit.edu
617-258-0952
Broad Institute of MIT and Harvard
Source:Eurekalert

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