Deborah Nickerson, arguably one of the leading forces of SNP research, did not start her scientific path with genetics in her sights. Her career officially kicked off after winning a predoctoral fellowship courtesy of the National Cancer Institute in 1974; four years later, she graduated from the University of Tennessee with a PhD in immunology. But we can thank Kary Mullis for capturing Nickerson's interest — enough to change her career path to genetic research. While on sabbatical, Nickerson stumbled upon PCR, at the time a game-changing new technology. She was immediately struck by the obvious potential PCR held for the elucidation of human genetics, and it was then that she took up the idea of exploring DNA as a lifelong pursuit.
Nickerson was involved in some of the early sequencing studies of human genes in populations. In 1990, along with Lee Hood and several others, Nickerson published a seminal PNAS paper that demonstrated the effectiveness of PCR for the diagnosis of common genetic diseases, such as sickle cell anemia and cystic fibrosis. "There were lots of applications using PCR as a front end in those days," she says. "In my view, today is again a turning point in human genetics, like PCR, but this time it is next-generation sequencing that will take center stage."
For more than a decade, the focus of the Nickerson lab has centered around SNPs in relation to cardiovascular disease risk in human populations. In addition to developing novel SNP approaches to apply in the exploration of human association mapping, the team is also investigating possible relationships connecting genotype and trait expression at RNA and protein levels in humans. Many of the early studies Nickerson worked on looked at natural variation in the population in a very unbiased way that led to several major SNP projects.
"We've probably sequenced and looked at variation in 1,000 genes already," she says. "I've been involved in some really large-scale projects that have looked at variation analysis, and it's been fun to scale up and do things in novel ways. We've also done some really neat association studies."
Not where she started
Nickerson, now a professor of genome sciences at the University of Washington School of Medicine, will be the first to tell you she is not your typical genomics investigator. "I trained as an immunologist; I'm not actually trained as a genomics person," she says. "So the way I trained was very different from the way I train people now, but that's because the field of genomics is something that only emerged over the last 20 years and that's where my career was built up."
Early on, after switching career tracks, Nickerson counted herself lucky to have legends like Maynard Olson and Phil Green, both professors of genome sciences and medicine at the University of Washington, to offer guidance on how to thrive as a budding genetics researcher. "I would say that I grew up as a young faculty member around some of the finest genome people in the country, so when you have colleagues like that who are awesome, it's very easy to learn how to do things," she says.
Nickerson says that the biggest challenges she faced when pursuing her graduate education and those that exist for her lab members today are essentially the same. "In any of these things, it's trying to define a project to see what works, what doesn't work, where headway can be made," she says. "Same thing for a postdoc. … The idea is to handle more things than what you handled as a graduate student and they need to find some things that are going to ultimately end up in their career."
As a PI, Nickerson aims to guide her students through these common, yet essential, growing pains in order to fully prepare them for their first job as faculty members. However, most of the time, she leaves well enough alone because she knows that students must fend for themselves to become effective and independent investigators. "I would say I'm more of a hands-off mentor," Nickerson says. "People have to find what is interesting to them and have the motivation to go after it and be able to choose what they're interested in."
When the time comes for her graduate students to depart from her lab and venture out into the great blue yonder, Nickerson hopes that they have picked up some very basic survival skills. "I hope they leave with an idea that they can interact with people outside of an individual group, because especially graduate students tend to be very internal," she says. "Postdocs will interface with larger projects where a graduate student may not be able to because it's harder to have a more long-term project like that."
Being one of the few female genomics pioneers, Nickerson definitely has an awareness of the state of gender equality in the lab. Even today, Nickerson says there can be different challenges for up-and-coming female researchers versus males. "In genomics I don't think there's an equal number of males and females, even though things have changed dramatically over time," she says. "There are still real issues that impact both genders' careers differently. And there is more sharing today than there was years ago, but there still has to be even more."
In order to try to address these issues, Nickerson takes an active role in a group for women in sciences organized by the school's genome sciences department. "I do think that there are issues, and both men and women attend the meetings to inform how can we go forward in ways that are 'unisex,'" she says. "I am very proactive about young women scientists certainly, as well as young male scientists, and I think the future of any area is only as good as the people coming up behind you — and that's graduate students, postdocs, and young faculty members."
Ultimately, Nickerson says that she benefited a great deal from being surrounded by senior colleagues who were leaders in genomics when she was first starting out. She adds that she certainly hopes to continue as a mentor to those who pass through her lab as long as she still has an active career. N
"I grew up as a young faculty member around some of the finest genome people in the country, so when you have colleagues like that who are awesome, it's very easy to learn how to do things."
The names below represent a handful of Nickerson protégés, some of whom you may have already seen featured in Genome Technology's special Young Investigator Profile series.
Carlson completed his postdoc with Nickerson more than 10 years ago and is now an assistant professor of epidemiology in the School of Public Health at the University of Washington, where he focuses on analysis of correlations between genetic variation and cancer, cardiovascular disease, and neurological disease.
A senior research fellow at the University of Washington, Cooper is balancing responsibilities in both Nickerson's and Evan Eichler's labs. He is currently working on mammalian genomics research as it applies to human genetics and population characterization.
Having learned well from her SNP mentor, Crawford is now an assistant professor of molecular physiology and biophysics at Vanderbilt University, where she combines both SNP data and epidemiology to study human populations.
After completing her graduate education under Nickerson's tutelage, Mackelprang went on to make headlines with her role in the unraveling of the Neanderthal genome. She is currently a postdoc focused on genetic analysis at the Department of Energy's Joint Genome Institute.
After riding out the high point of the genomics revolution in the late 1990s as a postdoc in Nickerson's lab doing comparative studies, Rieder headed to Wisconsin to take a position as a research assistant professor at the Milwaukee School of Engineering, where he manages a large-scale DNA sequencing laboratory.