W.M. Keck Foundation awards Jefferson scientists with $1M medical research grant

Scientists at Thomas Jefferson University have been awarded a $1 million medical research grant from the W.M. Keck Foundation for an ambitious project looking at the little explored 98 percent of the human genome and what role it may play in the onset and progression of diseases.

The multidisciplinary team, led by Computational Medicine Center at Jefferson director Isidore Rigoutsos, Ph.D., will soon begin studying a particular group of DNA motifs-genomic combinations of letters that repeat more frequently than expected by chance-called pyknons. Researchers and physicians will be looking at what function they serve in the context of several types of cancers, platelet aggregation properties, two autoimmune disorders, and type-1 diabetes.

Dr. Rigoutsos, a world-renowned computational biologist, originally discovered pyknons in 2005 using computational analyses. In the time since their discovery, evidence has been slowly accumulating that these pyknon motifs mark transcribed, non-coding RNA sequences with potential functional relevance in human disease.

"This is very exciting. The grant comes on the heels of six years of research," said Dr. Rigoutsos. "It will help us get to the bottom of this story: an unexplored territory that we strongly suspect has something important to reveal about human disease. There is disconnected evidence, and we want to assemble all the pieces."

For many years, Rigoutsos, who came to Jefferson in 2010 following a nearly 18-year tenure at IBM's Research Division, focused on generating conspicuous tidbits of evidence computationally, the result of his not having access to experimental facilities. All of this has, of course, changed at his new home: the Computational Medicine Center, which he founded at Jefferson last year.

Now, he said, he can cast a wider and deeper net by studying pyknons using samples from a diverse collection of human conditions: prostate, colon and pancreatic cancer, chronic lymphocytic leukemia, type-1 diabetes, hyper- and hypo-reactivity in platelets, multiple sclerosis, and systemic sclerosis. Dr. Rigoutsos is also a member of the Kimmel Cancer Center at Jefferson.

The goal is to investigate the presence of pyknon-marked non-coding RNAs in these conditions and determine the rules governing the biogenesis, processing, and mechanisms of regulatory action of these transcripts. The planned research activity will involve a combination of computational analyses and modern experimental techniques.

The winning team comprises researchers and physicians from the Computational Medicine Center and several Departments of Thomas Jefferson University and Hospital, the Children's Hospital of Philadelphia, the University of North Carolina at Chapel Hill, and the University of Texas' MD Anderson Cancer Research Center.

"It is a great honor to be recognized by the W.M. Keck Foundation, which has a long history of supporting innovative and pioneering medical research," said Mark L. Tykocinski, M.D., Dean of Jefferson Medical College and Senior Vice President of Thomas Jefferson University. "This is a unique award for a unique area of human genome research that, with our multidisciplinary approach, will undoubtedly pave the way for breakthrough discoveries to help better treat and prevent diverse diseases."

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