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Sue Ackerman's breakthrough research into basic mechanisms underlying neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and motor neuron disease has established her as a leader in the field.

Keeping a clear mind

by Luther Young / Photography by Ned Johnston

Sue Ackerman, Ph.D., was already imagining her future in genetics research as a college undergraduate in the 1980s, intrigued by the promise of unlocking the secrets of human disease.

But the seeds of her present career focus on neurodegeneration were planted not in a classroom, but in her dorm room. "I found out that my best friend in college's father had died of Huntington's disease. She knew she was 50 percent at risk, and in fact she has now been diagnosed with Huntington's," says Dr. Ackerman.

"It's one thing to learn about these diseases as an example in genetics class, but this was personal," she says. "And I hoped I could make a difference."

Now a full professor and sought-after mentor at The Jackson Laboratory, Dr. Ackerman, 47, has hit her exuberant mid-career stride. Her breakthrough research into basic mechanisms underlying neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and motor neuron disease has established her as a leader in the field. Her appointment as a Howard Hughes Medical Institute (HHMI) investigator, one of the top distinctions in American biomedical research, affirms her status.

Making a difference

Dr. Ackerman describes herself as "very driven." A Californian and oldest of four children, she graduated with dual B.A. degrees in biology and chemistry from California State University at Chico at age 21, then earned a Ph.D. in biology from UCLA in 1987, working as a teaching assistant in 17 separate undergraduate courses to pay her way through school.

Dr. Ackerman didn't fully grasp how she could "make a difference" until her postdoc in the mammalian genetics department at the University of Illinois College of Medicine. "I found I was really good at molecular biology, and I love the challenge of coming up with an idea and testing it in the lab," she says. Using mice as models for her human disease research, she employs an innovative strategy to track down specific genes associated with a disease, a painstaking process that can take "years of hard work."

It was the Laboratory's stellar reputation in the biomedical research world that lured Dr. Ackerman to Bar Harbor in 1994 as a research associate in Dr. Barbara Knowles' lab. "The resources here are too tremendous; they're just unique. I'm a displaced Californian—I wanted to live in a city, not on an island in the Arctic," she laughs. "But I came here, and thank goodness. It was the right decision for my career and for my family."

Dr. Ackerman and Doug McMinimy, supervisor of the Allele Typing & Sequencing service at the Laboratory, are the parents of two girls, Rachael, 13, and Caroline, 10. She credits her husband with much of her success at juggling family and career.

"Doug's the most supportive spouse in the world; he's made it possible for me to do all this," she says. "I talk with students, particularly the young women, openly and honestly about what it takes to make a career in research. They need to hear it. They need to know that it's 60 hours a week or more for the rest of their careers. You have to really want it. You're not going to be home baking cookies every afternoon for your kids."

A hotbed of activity

Her spacious lab in the new East Research Building — near many of her colleagues in the Laboratory's growing, highly interactive neurobiology group—is a hotbed of activity, often round-the-clock, with six postdocs, one graduate student and two research staff.

Dr. Ackerman works closely with her trainees and research staff in designing experiments for the multiple research projects under way into the mechanisms underlying defects in the development and maintenance of neurons in the cerebellum, the region of the brain responsible for motor control and balance.Dr. Ackerman's research, enabled by the Laboratory's wealth of resources for investigating neurological disorders, has consistently resulted in advances in neuroscience that have been published in such major, peer-reviewed journals as Nature, ;Nature Genetics, ;Journal of Neuroscience and ;Development—more than 40 publications since she arrived at the Laboratory.

An early project, still ongoing in her lab, targeted cell migration defects in the cerebellum during development, implicated in human disorders such as severe mental retardation and epilepsy. In 1997, she identified a gene mutation that disrupts the critical process during embryonic development in which newly born neurons migrate to precise locations in the brain and are wired into the intricate circuit that ensures proper brain function.

In 2002, Dr. Ackerman was investigating the harlequin mouse, which after maturity displays progressive movement problems, or ataxia, due to impaired cerebellar function. She identified a gene that was previously thought to promote cell death, but Dr. Ackerman showed for the first time that it is actually necessary for neuron protection and survival. The protective mechanism shields the neurons from damage that has been implicated to date in amyotrophic lateral sclerosis, or ALS, and may also be involved in other age-related neurodegenerative diseases and in tumor development.

Exciting developments

"Very exciting" is how Dr. Ackerman describes a recent research project that attracted widespread interest from the neurobiology community and the science media when it was published in the September 7, 2006, issue of ;Nature. The focus is protein misfolding, familiar to many as the signature process in Alzheimer's disease that clogs brain neurons with a toxic protein sludge and triggers cell death.

In her experiments, Dr. Ackerman used another mouse— known as "sticky"—that displays movement problems as an adult due to neuron loss in the cerebellum. And, surprisingly, she found that the neurodegeneration was caused not by a mutated gene, but by a mechanism involving errors in protein synthesis in brain cells. This mild "editing" defect, described for the first time in a mammalian system, results in malformed proteins and symptoms similar to those associated with neurodegenerative disease in aging humans."We think that fully understanding this process could lead to treatment, to stopping or slowing the progression of neurodegenerative disease in people caused by protein misfolding," Dr. Ackerman says. Her laboratory is now pursuing so-called modifier genes that can override the editing defect, and recently identified a modifier that suppresses neurodegeneration in sticky mice and could help identify a similar protective mechanism in humans.

The Nature publication came shortly after her HHMI appointment. In 2005 Dr. Ackerman joined colleague Simon John as one of the Laboratory's two HHMI investigators and the only such honorees in Maine. Designed to spur scientific discovery by the nation's most talented and innovative scientists, the program provides unrestricted research funding for five years, freeing recipients from the timeconsuming burden of seeking other grants.

"It's an incredible vote of recognition for our science," Dr. Ackerman says. "It has been wonderful to have the additional funds to use on new projects in the lab, and to have been affiliated with, and to meet, some of the most amazing scientists in the world."

Dr. Ackerman is committed to giving back to the next generation as a mentor for postdocs, grad students, and the high school students and undergraduates in the Laboratory's Summer Student Program, one of the top student research internships in the nation.

Her success and enthusiasm are an inspiration to young, aspiring scientists, and she believes the internships are a "fantastic opportunity for students who think they're going to be interested in research and maybe go on to grad school. They typically haven't had a real research experience, and they can see if this is a good fit for them."

Dr. Ackerman's dedication to mentoring young scientists surely was an added bonus to HHMI, which also funds the Summer Student Program and research internships for the University of Maine science teachers-in-training at the Laboratory. She remembers with pride her best students over the years, including one who earned a Ph.D. in neurobiology from the University of Washington and has gained national recognition as an authority on science policy and ethics, and another who is now pursuing a doctorate in biological chemistry at her own alma mater, UCLA.

"These students are more sophisticated than I was at that age," she says. "They're smart to work in a lab before grad school." Common qualities? "Their intelligence, of course, but more than that: their work ethic, and their natural curiosity. And good hands, too! Well, you can't tell that part of it until they get in the lab."

Sounds familiar to those who know Dr. Ackerman. Intelligence. Strong work ethic. Natural curiosity. And good hands.

And she loves being a scientist more every day. "There's no other job I can think of that I would like better," she says. "I'm doing what I want to do."