Seminal Discoveries in Metabolism Earn Biochemist Jared Rutter, Ph.D., HHMI Investigator Appointment

Seminal Discoveries in Metabolism Earn Biochemist Jared Rutter, Ph.D., HHMI Investigator Appointment

May 19, 2015 9:19 AM

WATCH VIDEO — A University of Utah biochemist whose research has significantly expanded the understanding of human metabolism–chemical processes that synthesize and break down the building blocks of cells–and its relation to disease has received a highly prized honor in the world of science: selection as an investigator with the Howard Hughes Medical Institute (HHMI).

HHMI announced today that Jared Rutter, Ph.D., U of U professor of biochemistry and Dee Glen and Ida Smith Endowed Chair for Cancer Research, is among 26 of the nation’s top biomedical researchers from 19 institutions nationwide selected as investigators this year. The initiative represents an investment in biomedical research of $153 million over the next five years.

Scientific discovery requires original thinking and creativity, and each of the investigators selected has demonstrated those qualities, according to HHMI President Robert Tijan. “One of the most important things we can do at HHMI is to continue to support and encourage the best discovery research,” Tijan said in an Institute news release. “We don’t know this for certain, but the ideas that emerge from these labs might one day change the world, and it’s our privilege to help make that happen.”

Rutter focuses his research on metabolism and mitochondria, self-contained units in cells that have crucial roles in metabolism. Metabolic processes break down carbohydrates and fatty acids in order to fuel production of ATP by mitochondria. ATP is the main source of energy for cells and is essential for humans and other animals to live.

“I am very grateful to all of the people that have contributed to making this happen.  I have been fortunate to have fantastic co-workers in my laboratory, fantastic colleagues in the Department of Biochemistry, in the Diabetes and Metabolism Center and throughout the University,” Rutter says. “Of course, I’m also very grateful to the Howard Hughes Medical Institute for putting their trust in me to do something meaningful with this award.  I am committed to make that happen."

A Utah native, he received his undergraduate degree in molecular biology from Brigham Young University and his Ph.D. in cell and molecular biology from the University of Texas Southwestern Medical Center in Dallas, TX. After completing a fellowship as the Sara and Frank McKnight Independent Fellow of Biochemistry at UT Southwestern, he returned to Utah to join the U of U School of Medicine faculty in 2003. Rutter also serves as co-director of the Diabetes and Metabolism Center at the University of Utah and as co-leader of the Nuclear Control of Cell Growth and Differentiation Program at the Huntsman Cancer Institute.

Rutter’s research, says Dean Y. Li, M.D., Ph.D., University of Utah Health Sciences chief scientific officer and associate vice-president for research, provides answers to basic questions about mitochondria that have profound implications for cancer, heart disease and other serious metabolism-related health problems. His work has opened up the field of metabolism research for people to start thinking about therapies.

“He was born in Utah and returned here to do science,” Li says. “He’s not only making important discoveries to understand metabolic-related diseases but also has founded a company developing drugs to treat those diseases–and he’s doing it here in Utah.”

Rutter is drawn to biology’s least explored areas, and since launching his research program in 2003, he has turned up answers to mysteries scientists have been trying to solve for decades.

His research identified two proteins, Mpc1 and Mpc2, that play a pivotal role in producing ATP from carbohydrates but also cause a potentially fatal neuromuscular disease. The finding, based on studies with yeast, fruit flies and DNA from family members of people with the unnamed neuromuscular disease, shows that when Mpc1 and Mpc2 are eliminated or mutated, ATP is not efficiently produced and serious health problems can arise. In addition to discovering the important role that the two proteins have in converting carbohydrates into energy, the study, done in collaboration with U of U human genetics professor Carl Thummel, Ph.D., laid the groundwork for further research into understanding metabolic defects in cancer and heart disease.

In a study last year related to that research, the Rutter laboratory described a significant discovery regarding the Warburg effect– changes in cancer cell metabolism that enable the disease to rapidly spread. They found that cancer selects against a protein complex comprised of the Mpc1 and Mpc2 proteins called the mitochondrial pyruvate carrier (MPC), and that reintroduction of MPC into colon cancer cells impairs properties of the cancer, including growth. The research suggests that changes in the way cellular fuel is used is an important driver of colon cancer and probably other cancers as well.  Understanding the Warburg effect has been of intense interest in recent years because of the potential to translate those discoveries into new cancer therapeutics.

Also last year, Rutter and two research colleagues discovered in a study with rodents that an enzyme involved in intracellular signaling, PASK, has an important part in promoting the metabolic syndrome, a group of conditions that increases the risk for developing heart disease, diabetes and stroke. A spinoff company that Rutter co-founded in 2009, BioEnergenix, is now developing a drug to fight metabolic syndrome and he hopes it will go into human clinical trials in a couple of years.

When a university faculty member becomes an HHMI investigator, HHMI takes over the payment of the faculty member’s salary and gives him or her an operations budget for personnel, supplies and equipment. In addition, investigators may submit requests to HHMI for funding of major equipment. HHMI investigators continue to be based at their home institutions, typically leading a research group of students, postdoctoral associates and technicians. They also become Institute employees and are supported by field staff throughout the country.

Rutter was selected as an investigator from a group of 894 eligible applicants nationwide. He plans to use his HHMI funding to continue researching metabolism and its relations to cancer, diabetes and other diseases. He joins three other U of U current faculty who also are HHMI investigators: Nobel laureate in medicine Mario R. Capecchi, Ph.D., distinguished professor of human genetics and biology; Bradley R Cairns, Ph.D., professor and chair of oncological sciences and Huntsman Cancer Institute investigator; and Erik M. Jorgensen, Ph.D., professor of biology.

Baldomero M. Olivera, Ph.D., U of U distinguished professor of biology, is an HHMI Professor, an honor given to researchers in recognition of their excellence in research and undergraduate teaching, HHMI Professor awards support innovative science education at the undergraduate level.

The Howard Hughes Medical Institute

The Howard Hughes Medical Institute is committed to advancing basic biomedical research and science education for the benefit of humanity. Its scientists, located across the country and around the world, have made important discoveries that advance our fundamental understanding of biology. In a complementary program at HHMI's Janelia Research Campus in Ashburn, Virginia, leading scientists are pursuing long-term, high-risk, high-reward research in a campus designed to bring together researchers from disparate disciplines. The Institute also aims to transform science education into a creative, interdisciplinary endeavor that reflects the excitement of real research. For more information, visit www.hhmi.org.

During fiscal year 2014, the Institute made disbursements of $919 million, including $706 million for biomedical research and $77 million in support of science education. The Institute’s endowment at the close of fiscal year 2014 stood at about $18.6 billion. HHMI’s headquarters are located in Chevy Chase, Maryland, just outside Washington, D.C.

 

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