Maureane Hoffman chose research to improve lives

The opportunity to improve people's lives through research is what first attracted Maureane Hoffman ('82 MD, PhD) to science. Today her discoveries are doing just that-improving understanding of blood coagulation and leading to better treatments for people with hemophilia and other blood clotting disorders.

Hoffman, who grew up in New Mexico, came to Iowa because she wanted to live in a small-town environment that had a "big-league educational program." She started a PhD program in pharmacology/toxicology intending to be a research scientist, but with the introduction of the UI's Medical Scientist Training Program (MSTP), she jumped at the chance and became a member of first MSTP class.

Maureane HoffmanAfter completing her MD/PhD in pharmacology/toxicology and a pathology residency and fellowship at Duke University, she joined the Duke University faculty before moving on to the University of North Carolina (UNC-CH). In 1991 she returned to Duke, where she is a professor of pathology and immunology, and director of the blood bank and hematology laboratories at Durham Veterans Affairs Medical Center. She has continued investigating an area she was drawn to during her time at the UNC-CH. At the time she was working on the role of monocytes in transfusion reactions. Her research focus began to change after a fruitful conversation with Dougald "Mac" Monroe, PhD, now an associate professor in the Carolina Cardiovascular Biology Center at UNC-CH.

"I had all these platelets contaminating my blood monocyte preps," she said. "I was talking one day to Mac, who was studying coagulation proteins such as factor IX, using phospholipids as a surface for these proteins to bind to. I told him he ought to do that on all these crummy platelets I had, and that was the beginning of our collaboration."

Hoffman's main project for the last 20 years has been exploring the role of cells in controlling blood clotting.

"The prevailing view of coagulation was that two coagulation pathways converge to make thrombin to clot the blood," Hoffman said. "If both pathways made thrombin, then having one defective pathway shouldn't present much of a problem. However, we knew that people with hemophilia have one normal pathway but still have bleeding problems.

"In order to find out why this is the case, we needed to find out which specific roles each pathway had, and that was the question that got us started," she added.

The investigators faced a major obstacle, however - the fact that it was very difficult to examine the details of the coagulation process in animals. So Hoffman and Monroe tried reassembling the coagulation process in tissue culture plates, adding human monocytes as a cellular source of tissue factor, purified coagulation proteins, inhibitors, and human platelets.

"We thought this would be a better reflection of what happens in the body, and it turns out it is," she said.

Now Hoffman and other collaborators, including Harold Roberts, MD, professor of hematology at UNC-CH, are able to manipulate the concentration of each component and see how that affects coagulation-something that can't be done in real plasma or animal models.

With this model, Hoffman's team has found that both pathways do different jobs in the body, and both are needed to coagulate the blood. The new model has also shed light on why a relatively new drug, recombinant factor VIIa, works for people with hemophilia.

Her team is also working on a project studying coagulation as it relates to wound healing. Hoffman's team is investigating what goes wrong when people bleed excessively following trauma or surgery, and related to that, how much the blood can be diluted in emergency situations before coagulation is affected. Two other projects - investigating what happens in liver disease, where many coagulation factors are synthesized, and studying the role of homocysteine in thrombosis keep Hoffman's lab humming.

The wide array of projects, as well as her enthusiasm discussing them, shows how fascinated Hoffman is with her work. It's not surprising that science is her passion. She grew up with a chemist mother and a physicist father, both now retired. Her brother caught the bug as well and is now a plastic surgeon in California. Add to the mix Hoffman's sister-in-law, who is an internist, and family gatherings can get interesting.

"If someone calls asking for Dr. Hoffman, it's never clear who they'll get," Hoffman said.

Having her parents' support eased the road for Hoffman to explore a science career, especially at a time when men still dominated the field.

"There was a book my parents got for me when I was 10 or 11 about all the key people and discoveries in medical science," she said. "I still remember that book and how fascinating it was that people discovered things by experimentation and those discoveries had a huge impact on patient care. I think that's why I thought research was the thing to do. If you're a practitioner you can affect hundreds or thousands of people in your lifetime at most, but as a researcher you can affect millions. Even if you don't make a huge discovery, you are part of a process that ultimately makes things better for people."