The Howard Hughes Medical Institute on May 9 announced the selection of Chuan He, professor in chemistry and the current director of the Institute for Biophysical Dynamics at the University of Chicago, as a new HHMI investigator.
“The Hughes support will put us in a good position to uncover some unpredictable science,” said He, whose investigator appointment will take effect in September.
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He was one of 27 mid-career biomedical researchers selected from a group of 1,155 applicants.
The institute provides investigators their full salary, benefits and a research budget over their initial five-year appointment. The institute also will cover other expenses, including research space and the purchase of critical equipment. Appointments may be renewed for an additional five years, contingent upon a successful scientific review.
“HHMI has a very simple mission,” said Institute President Robert Tjian. “We find the best original-thinking scientists and give them the resources to follow their instincts in discovering basic biological processes that may one day lead to better medical outcomes.”
He brings a chemist’s perspective to biological problems. His research team relies heavily upon genomics tools, along with expertise in chemistry, biochemistry, cell biology, molecular biology, structural biology and microbiology. “It’s a very diverse research environment in the lab,” He said.
His work has shed light on the roles of metals in biological systems, identified bacterial regulators of virulence and antibiotic resistance, illuminated mechanisms of DNA repair, and revealed new modes of genetic regulation. He now wants to understand how the addition and removal of methyl groups on genetic material reversibly alter gene activity.
Such modifications to DNA are well known to influence how the genetic code is read. In 2011, He’s group showed that reversible modifications to RNA can have similar effects. He found that the most prevalent internal methylation on human messenger RNA—methylation of the nucleoside adenosine—is reversible and could affect protein levels in cells.
His lab went on to demonstrate that two functionally significant human proteins, FTO and ALKBH5, remove methyl groups from RNA, and these processes affect obesity, type II diabetes and fertility. He now plans to continue exploring the scope, mechanism and effects of reversible RNA methylation in biological regulation.
“I believe this is an entirely new research area and we are uncovering new biological pathways,” He said. “There are many questions we need to answer. The Howard Hughes Medical Institute provides the perfect resource and the support that allows us to explore all the interesting directions of fundamental biology of this reversible RNA methylation.”
He’s laboratory also is known for developing chemical technologies to label and sequence a recently discovered chemical modification in DNA—5-hydroxymethylcytosine, or 5hmC—that is particularly abundant in the brain. Current research suggests that 5hmC is an intermediary molecule produced when DNA is demethylated and it may directly impact gene activity in various cells. He’s tools made it possible to detect and survey the exact locations of 5hmC as well as its further oxidized derivatives, such as 5-formylcytosine, or 5fC, in the mammalian genome. His latest work on 5fC was just featured as one of two back-to-back papers on the cover of Cell. He will continue to explore their functional roles as well as the mechanism of demethylation.
“My lab is developing the most effective methods to map DNA demethylation in the human genome,” He said. “We utilize these methods to uncover the mechanisms, the functions, and implications in human diseases associated with DNA demethylation.”
A non-profit medical research organization, HHMI was established in 1953 by aviator-industrialist Howard Hughes. The institute, headquartered in Chevy Chase, Md., is one of the largest philanthropies in the world, with an endowment of $16.1 billion at the close of fiscal year 2012.
—Prof. Jacqueline Stewart
