Detail-oriented, with an eye on the big picture

A picture of Allison Andraski in the lab.

Allison Andraski, PhD ’19, bridges her passion for research with her interest in health by studying the little-understood world of HDL, or “good” cholesterol.

May 22, 2019 – In her senior year at UC Santa Barbara, Allison Andraski began working in a laboratory on campus that was studying Botryllus schlosseri, a funky little sea creature that looks like a flower, grows in colonies, and can be found living on the outside of mussel shells. Each week, members of the lab would go down to the nearby harbor, scoop up buckets full of mussels, and bring them back to the lab. There, they would grow new colonies of B. schlosseri, which were a good model organism for studying innate immunity, the system that provides an organism with a natural first-line defense from a wide variety of pathogens.

Andraski, who grew up in Minden, Nevada and worked as physical therapy technician in high school, had always been curious about human health but wasn’t quite sure what career track she wanted to pursue. The more time she spent in the lab, though, the more she began to think about pursuing research as a career.

“I loved the research process,” she said. “And I began wondering, do I want to do medicine or do I want to do research? Or can I somehow combine the two?”

Andraski didn’t have to make up her mind right away. Rather than hunkering down for medical school entrance exams or plunging into a PhD program, she accepted a postbaccalaureate intramural research training award from the National Institutes of Health (NIH). At the NIH, she landed in the laboratory of Dr. Warren J. Leonard, an esteemed immunologist, and began working on projects analyzing signaling pathways in the immune system. After two years at the NIH, Andraski had her heart set on finding a research position that allowed her to ask big, difficult questions and set up experiments to find the answers. “I realized how powerful research can be,” she said, “and how it can translate into discoveries that directly help patients.”

At the urging of Leonard, Andraski applied to the PhD program in biological sciences in public health based at Harvard’s Graduate School of Arts and Sciences. When she was accepted, she says, it felt like a world of possibilities opened up before her. Andraski, who received an American Heart Association Predoctoral Fellowship and support from the Irene M. & Fredrick J. Stare Nutrition Education Fund, was immediately drawn to the laboratory of Frank Sacks, professor of cardiovascular disease prevention at Harvard T.H. Chan School of Public Health. She was excited by the fact that Sacks focused on working with data collected solely from human studies, which she saw as having great potential for high-impact research. Sacks’ laboratory proved to be the perfect setting to bridge her interest in medicine and human health with her passion for research.

“Allison has an unusual maturity in her scientific thinking, especially with regard to her ability to put individual results into a larger framework,” Sacks said. “Scientists have to be able to be detail-oriented, and at the same time, really outstanding scientists have to see the bigger picture, and Allison always seems to do that.”

Working with Sacks turned Andraski on to the critically important yet little understood world of high-density lipoprotein (HDL), which is often referred to as “good cholesterol.”

HDL has long baffled scientists and drugmakers. It’s thought that HDL is a beneficial lipoprotein, or cholesterol-carrying particle, and there is ample evidence that people who have higher HDL levels have much lower risk of heart disease. Yet, as Sacks noted, there is no good way to treat low HDL levels in order to make HDL more protective. There have been clinical trials aimed at doing so, but, according to Sacks, many of them have failed because they adhered to an overly simplistic notion that raising the blood level of HDL reduces heart attacks.

Andraski’s research built on previous findings from Sacks’ lab and helped reveal the true complexity of HDL. She began analyzing the characteristics of HDL particles and probing the metabolism and functions of the more than 100 proteins that are bundled around HDL particles. On top of that, she set up a study to see whether different diets affect the different proteins on HDL particles.

“What Allison has shown is that there are whole sets of subsystems or metabolic systems within HDL. And these systems are formed by proteins that the liver attaches to HDL as the HDL particles are synthesized,” Sacks said. “Some of the proteins are protective against heart disease and others, for some reason, have adverse effects. In a sense, this is kind of a new framework of thinking about HDL that improves our chances of finding ways to harness its protective benefits.”

William Mair, associate professor of genetics and complex diseases and a member of Andraski’s thesis defense committee, said the outcome of her work was intriguing because it showed that “maybe not all good cholesterol is created equal.”

As with so many scientific endeavors, Andraski’s research has led to more questions than answers. And she couldn’t be happier.

“For me, this is a really exciting time to study HDL. There are so many things we don’t yet understand, which also means there are a lot of things to be discovered,” she said. “I think the methods we have developed to look at HDL proteins in humans will allow us to follow up and actually figure out what’s going on with this system.”

Chris Sweeney

Photo: Sarah Sholes