UA Cancer Center Scientist Recognized for 'Bold Approach to Major Challenges in Biomedical Research' through NIH Transformative Research Award

Keith Maggert, PhD, a research scientist at the University of Arizona Cancer Center, has received a prestigious Transformative Research Award (TRA) and a five-year, $1.7 million grant from the National Institutes of Health (NIH) to fund his research program, “Induced Transgenerational Inheritance Without Epigenetics.”

Investigators previously have attempted to use drugs that target epigenetics to treat diseases. Dr. Maggert’s work demonstrates why these treatments, in general, largely have been ineffective and in some cases even toxic. With the knowledge gained by this research, Dr. Maggert will seek to identify new and effective treatments for epigenetic diseases, such as cancer.

Epigenetics is the study of stable changes in gene function that are passed from cell generation to cell generation. For instance, a gene can be silenced through epigenetic changes that are inherited in the absence of genetic mutation. Dr. Maggert’s transformative research is a new way to conceive of the field of epigenetics that challenges the current model and seeks to build a new paradigm to characterize epigenetics.

Although a somewhat controversial area, epigenetics has the promise for transformational discovery in the world of medicine and health care. Researchers, government agencies and the news media have devoted much attention to epigenetics because of its role in the development of numerous human diseases, such as cancer, dementia and diabetes. Enormous potential exists to impact treatments for disease if researchers could learn to better manipulate epigenetics.

“My experiments have challenged entrenched concepts in the field of epigenetics,” said Dr. Maggert, who is a UA associate professor of cellular and molecular medicine and a member of the Cancer Biology Program at the UA Cancer Center. “So far, it has been exceedingly difficult to get this work funded because I have shown that most of what we know about epigenetic inheritance—a major sub-discipline in genetics and disease research—is misunderstood at a very basic level.”

Diseases like cancer and diabetes are caused by many factors, including genetics, the environment and random chance. Researchers and physicians have known for some time that the risk of disease increases as people age (explaining things like the generally late onset of dementia, cancer, etc.). In some cases, the increased risk for disease can even be transmitted to a person’s children. Epigenetics has been profoundly difficult to study, and as a result, many of the ways researchers think epigenetics works only recently have been proven incorrect.

The NIH recognizes the extreme potential in Dr. Maggert’s unique approach, tapping him among a cadre of researchers throughout the nation as “highly creative and exceptional scientists with bold approaches to major challenges in biomedical research.”

The TRA is part of the “High-Risk, High-Reward” set of grants, designed to support “transformative” research that overturns current research paradigms. It is highly prestigious—in 2016, only 3.8 percent of applicants received the award—and Dr. Maggert’s work was funded because it is expected to change the way researchers think about all epigenetics in disease.

“Dr. Maggert’s work is transforming the way we understand trans-generational epigenetic inheritance,” said Nathan Ellis, PhD, director of the Cancer Biology Program at the UA Cancer Center and associate professor in the UA Department of Cellular and Molecular Medicine. “The research has the potential to impact disease treatments that are based on manipulation of epigenetics.”

The research program, “Induced Transgenerational Inheritance Without Epigenetics,” is supported by the NIH under award number R01-GM-123640.

Research articles related to this award include:

commentary: Maggert KA. (2012). Genetics: Polymorphisms, Epigenetics, and Something In Between. Genetics Research International, 867951.

commentary: Deans C, Maggert KA. (2015). What Do You Mean ‘Epigenetic?’. Genetics, 199: 887-896.

research: Aldrich JC, Maggert KA. (2015). Transgenerational Inheritance of Diet-Induced Genome Rearrangements in Drosophila. PLoS Genetics 11(4): e1005148.

research: Paredes S, Maggert KA. (2009). Ribosomal DNA contributes to global chromatin regulation. Proceedings of the National Academy of Sciences U.S.A., 106: 17829-34.