Living a life of extremes: Lisa Miller of BNL

Lisa Miller lives a life of extremes. At work, she looks inside brain and bone cells through some of the highest-tech equipment in the country, checking the chemistry of diseases like Alzheimer’s and osteoporosis. In her free time, the Brookhaven National Laboratory’s Associate Division Director climbs mountains, looking out at the world from the planet’s highest peaks.

Using mid-infrared light, Miller, who is in BNL’s Photon Sciences Directorate, has shown that some areas of the brains of people afflicted with Alzheimer’s disease have high amounts of metals like copper and zinc.

“Metals in our body are tightly regulated and are bound to proteins,” Miller explained. On their own, the metals could be “toxic and can kill cells.”

The brains of people who suffer from Alzheimer’s have amyloid plaques, where brain cells are folded over and clumped together. These plaques have high amounts of these metals.
Using the National Synchrotron Light Source (one of only four such Department of Energy funded tools in the country), Miller wanted to examine how the metals might build up in the brains of those with Alzheimer’s.

Because the concentration of iron in the amyloid plaques is ten times higher than normal, the presence of this metal could be an important diagnostic tool.

MRIs and other tools in doctors’ offices can measure the concentration of iron in a person’s brain.

“It’s possible to image patients who don’t have symptoms yet for high iron content,” Miller offered. Miller cautioned that it’s unclear whether there is a direct connection between the presence of these metals and the onset or course of Alzheimer’s disease.

Indeed, the BNL faculty plans to examine the link between copper in the plaques with disease severity. If the presence of metal is an important part of the progression of the disease, it shouldn’t show up in people who have amyloid plaques but don’t have symptoms. Miller is helping to hire scientists and engineers at BNL to build the next generation light source that uses x-ray, ultraviolet and infrared light. The NSLS-ii, which will be complete in March of 2014, will produce x-rays that are more than 10,000 times brighter than the ones from the current NSLS.

“She’s taken an active role in managing the facility,” said Antonio Lanzirotti, a senior research associate at the University of Chicago who collaborated with Miller on her Alzheimer’s studies. “She’s incredibly impressive in terms of her breadth of knowledge. People respect her opinion at the highest level of management.”

In addition to Alzheimer’s, Miller has also used the NSLS to study osteoporosis.
Partnering with biomedical engineer Stefan Judex at Stony Brook University, Miller and her lab have looked at how osteoporosis drugs affect the chemistry and strength of bones.
Fosamax and Actonel “work really well, not only in slowing down the resorption of bone,” she said, but also in helping the body produce “good, quality bone.”

When she’s not studying the chemistry of bones, brains and other tissues, Miller is an enthusiastic backpacker. She has climbed to highest point in 48 of the 50 U.S. states. Last year, she trekked to the top of Mt. Kilimanjaro.

A native of Cleveland, Miller took her first hike when her father “dragged us to the top of Mount St. Helens” when she was in graduate school at the Albert Einstein College of Medicine. Once she got the climbing bug, she couldn’t stop.

Miller believes in helping the next generation of researchers reach its own scientific peaks.
She helped start a new BNL program called Introducing Synchrotrons into the Classroom (called InSynC) that allows high school students to design research studies that use BNL’s synchrotron.

The projects, which go through a competitive review process, give students and teachers a chance to test their ideas using the NSLS. Miller credits her advisors with guiding her career and wants to pass that long.

“I always had good mentors,” she recalls. “If you’re excited about something, you want others to be as well.”