Student Profile: Nicole Paulk
09/29/09 Portland, OR
Don’t get in Nicole Paulk’s way. When this 25-year-old third-year PhD student at OHSU decides on a goal, she’s unstoppable. She has managed time after time in her short career to line up the right jobs, find just the right mentors, and scare up the necessary financial support to speed the way to her next objective.
She's doing it now in the Program for Molecular and Cellular Biosciences (PMCB) in the Department of Cell and Developmental Biology. She passed her PhD qualifying exam a few weeks ago, freeing her to focus entirely on her research project.
As a girl in Mt. Vernon, Washington, she spent summers as a kid picking cucumbers and strawberries and was the first in her family to graduate from college. She now spends most of her waking hours in Oregon Stem Cell Center lab directed by Markus Grompe, MD, Professor of Pediatrics and of Molecular & Medical Genetics, searching for a way to use gene therapy to repair a mutation that causes a rare metabolic disorder in children born with the defect called hereditary tyrosinemia type I.
"These kids," she explains, "have a mutation in an enzyme called fumarylacetoacetate hydrolase, which is needed to break down an amino acid in protein called tyrosine. The result is that tyrosine and other byproducts build up to toxic levels in their systems and can basically cause end-stage liver failure and kidney failure. If they don't get a liver transplant or some other therapy they'll probably die."
Traditional gene therapy seeks to treat diseases by providing the patient with a supplemental good copy of the gene to make the needed protein, but it doesn't fix the defective gene. The kind of gene therapy Nicole is working on – true gene repair – would actually repair the defect.
"By sending a benign adeno-associated virus into the body with just a fragment of the genomic sequence for the non-mutated gene, not the whole thing, the mutation is fixed through the magic of DNA repair," she said. "So nothing is removed that shouldn't be and nothing extra is inserted. All we're doing is fixing that one tiny mutation and then the virus goes away and you're literally cured forever. You don't need any medicine, you don't need any organ transplants. But this is pretty new. It's only been done in mice; it's never been tested in monkeys; it's never been done in humans. We're one of the first labs pioneering this technology."
Nicole – or Niki as her friends call her – is the first OHSU grad student to have won a coveted National Institutes of Health NRSA (the Ruth L. Kirschstein National Research Service Award) predoctoral fellowship as early in her career as she did, at the age of 23. She won it before she even started grad school.
"I've never heard of anyone doing that before," said Allison D. Fryer, PhD, Associate Dean for Graduate Studies. "I've never heard of any student coming in at the very beginning of her graduate career and saying, 'I've already got my NRSA.'" To read more, click here.
Because the NRSA award came so early, by the time Nicole gets her doctorate two years from now, the fellowship will have yielded nearly a third of a million dollars to support her PhD thesis project and OHSU.
Nicole's passion for the research she's doing and for the Grompe lab is palpable. "The most exciting thing about Markus's lab," she says, "is the literal electricity when everyone is cookin'. You can see people on the verge of a discovery right next to you and across from you and behind you, and that really motivates you to keep going."
Nicole started college aiming for a business degree. But she took some science courses as a fluke and was intrigued. She transferred to Central Washington University as a sophomore where she did some field research on frogs, and was permanently hooked. She found a mentor – an environmental and analytical chemistry professor named Anna Johansen – hired her as a lab assistant for a National Science Foundation project and spent hours indoctrinating her on the life of a scientist and what it takes to succeed.
Three days after graduating magna cum laude from CWU in 2006 Nicole went to work for Grompe as a Research Assistant running his mouse colony with the idea of paying off some student loans before going on to graduate work – and that's when she applied for the NRSA fellowship.
"I was thinking there's no way I'll win one this year, but this'll just be good practice. Then one day I got a short little e-mail saying 'Congratulations.' No big envelope or anything. Just an e-mail. And I freaked out. The whole lab freaked out. Then they said, 'How did you do it? You're just a technician.' And I said: 'I guess they liked my idea.'"
One vignette offers a measure of Nicole Paulk's mettle. When she was at CWU she got wind of an upcoming medical relief trip to Kenya and Tanzania to be partly staffed by pre-med students from the University of Washington and she wanted to go. But she was waved off. She begged. They said no dice. She begged again. They adamantly refused. "You don't go to UW, you're not a pre-med student (her major was microbiology) and, besides, it will cost you $4,000 and we're leaving in three weeks." Undaunted, she countered: "What if I could raise the money?" Confident the money obstacle would be impossible to surmount, they relented. And Nicole went to work. She typed up a pitch letter, got a team of friends together to stuff 300 envelopes, sent it to family, friends, famous athletes, people like Bill Gates and others. And in two short weeks, she had the money. Shortly thereafter she was on a plane to Nairobi and spent the summer helping treat people in isolated communities on the African savanna where few doctors had ever visited before.
The moral: Don't tell Nicole Paulk something is impossible. She just may prove you wrong.


