TWO UMASS MEDICAL SCHOOL SCIENTISTS HONORED BY THE W. M. KECK FOUNDATION
Prestigious awards support innovative biomedical research

July 31, 2007

WORCESTER, Mass.—The University of Massachusetts Medical School (UMMS) has been awarded two prestigious honors from the W. M. Keck Foundation: Stephen J. Doxsey, PhD, professor in molecular medicine, biochemistry & molecular pharmacology and cell biology, was awarded a Keck Medical Research Grant for the project entitled “A New Paradigm for Longevity;” and Job Dekker, PhD, a faculty member of the program in gene function and expression and assistant professor of biochemistry & molecular pharmacology, has been named a Keck Distinguished Young Scholar in support of his project, “Unraveling Chromatin Interaction Networks that Regulate the Human Genome.”

Established in 1954 by Superior Oil Company founder William Myron Keck and now one of the largest private philanthropic organizations in the country, the Keck Foundation supports the work of leading researchers to lay the groundwork for breakthrough discoveries. The Medical Research Program seeks interdisciplinary collaborations among established investigators with the potential to advance the frontiers of medicine, while the Distinguished Young Scholars in Medical Research program specifically addresses the difficulty the nation's most promising young scientists have in securing traditional sources of funding to pursue potentially groundbreaking research early in their careers, despite the fact that this period is often when they make their boldest discoveries.

Nominations from institutions are accepted on an invitation-only basis. The application process for both honors is rigorous and lengthy, requiring a major investment of time and resources on the part of the institution and the individual investigators, and thus reflecting their commitment to innovative research. “The fact that the Keck Foundation has recognized two of our faculty members with a major research grant and a Distinguished Young Scholar Award is further testimony to the outstanding research enterprise that has been developed here at UMass Medical School,” said Vice Chancellor for Research John L. Sullivan, MD, professor of pediatrics, molecular medicine, molecular genetics & microbiology and pathology.

Drs. Doxsey and Dekker are the institution’s first Keck recipients in the five years since Phillip D. Zamore, PhD, the Gretchen Stone Cook Chair in Biomedical Sciences and professor of biochemistry & molecular pharmacology, achieved the honor in 2002.

Doxsey’s project, “A New Paradigm for Longevity,” examines whether aging may be a curable disease of the stem cells rather than an inevitable process. It is this outside-the-box thinking encouraged at UMMS that is being supported by the $1.5 million Keck grant.

Doxsey and an interdisciplinary, intramural group of collaborators will study how asymmetric cell division affects aging and longevity, building on his lab’s remarkable finding published by Cell in 2005. “Our work reverses the accepted notion that human cell division creates two equivalent ‘daughter’ cells,” said Doxsey. “Rather, we discovered a process that produces cells with different life spans through asymmetric cell division.”

He explained that immortal stem cells and some cancerous cells inherit the original centriole and accumulate midbodies, which are essential structures for division. In contrast, the cells that lack midbodies and receive a copy of the centriole instead of the original are destined to die. These findings have critical implications for human life span, stem cell self-renewal, cancer cell immortality, aging disorders and neurodegenerative dementias. “The goals of our project are to test whether cellular longevity contributes to human life span with a set of experiments designed to address the mechanism, significance and clinical applications of midbody inheritance in human stem cells and cancer cells,” said Doxsey. 

“Dr. Doxsey’s exciting discoveries and his great leadership abilities in collaborating with an outstanding group of scientists have combined to make this an irresistible proposal for the Keck Foundation. He and the entire group of scientists involved should feel very proud about this breakthrough for UMass Medical School in obtaining its first consortium grant from the Keck,” said Professor and Chair of Molecular Medicine Michael P. Czech, PhD.

A leader in the study of cell division, Doxsey received his undergraduate degree from the University of Connecticut and his PhD in cell biology from Yale University. He completed a post-doctoral fellowship at the University of California at San Francisco before coming to UMMS in 1993.

In funding the exceptional research conducted at UMMS, the Keck Foundation will also support Dekker as a Keck Distinguished Young Scholar for his project “Unraveling Chromatin Interaction Networks that Regulate the Human Genome.” A special program of the Keck Foundation, Distinguished Young Scholars in Medical Research awards grants of up to $1 million to each of five junior faculty investigators at leading research universities and institutions annually. Dekker intends to map the three-dimensional organization of the genome inside cells, which may reveal how the genome normally works, as well as what goes awry to produce disease states, often characterized by alterations in the spatial organization of the genome. “Insights into the mechanisms that modulate the spatial organization of the genome will greatly contribute to a better understanding of gene regulation and may reveal causes of human diseases that are due to defects in these processes,” Dekker explained.

He will employ his own invention, the cutting-edge Chromosome Conformation Capture technology, called 3C, to detect physical interactions between genes and other genomic elements believed to be regulators. He will also employ 3C-Carbon Copy, or 5C, his further refinement of the 3C technology that dramatically increases throughput to analyze millions of interactions simultaneously. “Our project is very ambitious, which is what the Keck Foundation looks for,” said Dekker. “Ambitious undertakings are high risk, but when they work they have high payoffs. The Keck funding will enable us to use the available technology to its fullest potential to understand the basic workings of the human genome as well as the molecular basis of human disease.”

“Dr. Dekker is a very talented young scientist who had the courage and foresight to apply traditional chemical cross-linking techniques to probe the 3D structure of chromatin,” said C. Robert Matthews, PhD, the Arthur F. and Helen P. Koskinas Professor and chair of biochemistry & molecular pharmacology. “When the vast amount of data that he will generate is analyzed with bio-informatics methods, he will be in a position to obtain unique and valuable insights into the relationship between chromatic structure and gene expression.”

Dekker received his BS and PhD from the University of Utrecht, The Netherlands, then came to the United States for a post-doctoral fellowship at Harvard University before joining the UMMS Program in Gene Function and Expression in 2003. He is a member of the NIH’s National Human Genome Research Institute’s Encyclopedia of DNA Elements (ENCODE) consortium. Dekker has previously been honored by The Medical Foundation’s Charles A. King Trust, the Netherlands Organisation of Scientific Research and the European Molecular Biology Organization.

About the W. M. Keck Foundation
The W. M. Keck Foundation was established in 1954 by the late W. M. Keck, founder of the Superior Oil company. The Keck Foundation’s grant making is focused primarily on pioneering efforts in the areas of medical research, science and engineering. The Keck Foundation also maintains a Southern California grant program that provides support in the areas of civic and community services with a special emphasis on children and youth.

About the University of Massachusetts Medical School
The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research.  The Medical School attracts more than $174 million in research funding annually, 80 percent of which comes from federal funding sources. For more information, visit www.umassmed.edu.  

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