Matthews Lab
Rowena G. Matthews
Rowena Matthews was born in Cambridge, England, and raised in Madison, Wisconsin, where her father was on the faculty of the University of Wisconsin. As an undergraduate at Harvard, she worked in the laboratory of George Wald, who later won the Nobel Prize for his work on Vitamin A. A 1963 paper Matthews published in Wald’s lab has been cited over 250 times since the citation index was first developed a decade later, and was reprinted in Benchmark Papers in Biochemistry, Vol. 3, in 1982. This paper described the intermediate R* or metarhodopsin II, the first active form of a G-coupled receptor to be described.
Matthews moved to Michigan in 1963, and did her dissertation research with Professor Vincent Massey. Married with two young children by this time, she performed postdoctoral research with Professor Charles Williams. During that time, she continued with a theme that pervades much of her research to this day. As a chemist she has been interested in the role dietary vitamins and vitamin-derived cofactors play in catalyzing complex biochemical reactions.
Matthews became an Assistant Professor at the University of Michigan in 1975, and began focusing primarily on the mechanisms of enzymes and cofactors derived from the vitamins B12 (cobalamin) and folate, or folic acid. Much of this work focused on one folate-dependent enzyme, methylenetetrahydrofolate reductase (MTHFR). Her laboratory succeeded in the difficult process of purifying the enzyme from pig liver for study and later obtained peptide sequence for about 40% of it as well.
"I'm married to an orthopedic surgeon who used to look at me over the breakfast table and ask 'well, what have you done for humans lately?'" Matthews recalls.
Her answer came, quite unexpectedly in the early 1990s, after decades of meticulous basic science research. Matthews' inquiry into the fundamental biochemistry of vitamins turned out to be holding the solution to a question that clinicians had come at from the opposite direction. Physicians had found that elevated levels of the amino acid homocysteine was a factor in heart disease. And they knew that people with higher folic acid levels due to their diet somehow maintained lower homocysteine levels in their blood.
Matthews already understood how MTHFR catalyzed a chemical reaction that supplied the methyl group necessary for the conversion of homocysteine to methionine. Methionine is an essential component for the synthesis of human proteins. And in 1995, she and McGill University geneticist Rima Rozen identified the gene that makes MTHFR. Matthews knew that "our enzyme" was at least one of the proteins involved in managing the blood homocysteine levels, and could be playing a key role in this risk factor for cardiovascular disease and neural tube defects in babies.
It wasn't long before she and Rozen had identified a single-nucleotide difference in the genes of some people that apparently affected their ability to make MTHFR. Indeed, this tiny mutation was found to correlate with higher levels of homocysteine, especially in patients with low folate levels. Humans with the variant gene on both of their chromosomes had elevated levels of homocysteine, particularly if their folate intake was low.
Matthews and U-M biochemist Martha Ludwig have shown that structurally, the one-basepair difference resulted in a form of MTHFR that wouldn't function as it should to allow conversion of homocysteine to methionine. Fortunately, folate consumption in the diet can be increased to help the people who have these genes. People carrying two copies of this allele have a particular need for folate to keep their homocysteine in check. Recently, her lab also determined that folate protects the mutant form of the enzyme from losing its ability to function.
A few years ago, the USDA began requiring folic acid supplements in grain products. Since then, there has been an average drop of 22 percent in the homocysteine levels of Americans. Now Matthews, along with "almost everyone I know in the homocysteine field," takes vitamin supplements with folate.
In 2002, Rowena Matthews was elected to the prestigious National Academy of Sciences. In 2004, she was named to the Institute of Medicine, and in 2005 she was elected
to the American Academy of Arts and Sciences.
Rowena G. Matthews
