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Read more about Fred Hutch achievements and accolades.
The National Institutes of Health is the largest funder of cancer research in the world, so any edge a young investigator can get in the competition for NIH grants makes a difference in building a career.
Two postdoctoral researchers at Fred Hutch Cancer Center have won an important early career NIH training award that increases their chances of future NIH funding.
Adrianne Wallace-Povirk, PhD, and Anderson Frank, PhD, have both won a Ruth L. Kirschstein National Research Service Award Individual Postdoctoral Fellowship.
That’s a big deal because NIH grants comprise about 75% of the total sponsored funding at Fred Hutch, which consistently ranks among the top independent research institutes in NIH funding dollars.
Wallace-Povirk received a two-year fellowship worth about $151,000 to find new drug targets and anticipate potential drug resistance combatting a particularly aggressive form of pancreatic cancer.
Frank received a three-year fellowship worth $234,000 to better understand a complex cellular mechanism that helps cells properly divide.
The fellowships, also known as F32 awards, prime the pump for future NIH grants supporting projects spearheaded by principal investigators running their own labs.
Winning an F32 award increased the probability of receiving subsequent NIH research awards by nearly two percentage points, according to a 2018 working paper by the National Bureau of Economic Research. Receiving the award increased the chances of receiving an NIH-funded RO1 award — which supports mature, hypothesis-driven research projects with strong preliminary data — from 4.6 to 6.1 percentage points.
“The true value of the NRSA F32 award is its power of developing and conducting a research project and the freedom it gives the postdoc to explore that line of research under the supervision of their mentor,” according to the study.
Playing chess with cancer
Wallace-Povirk’s project stems from pancreatic cancer research by her mentor, Sita Kugel, PhD, in the Human Biology Division of Fred Hutch.
“It is wonderful having Adrianne in the lab,” Kugel said. “Her excitement for science is contagious! She is hardworking, focused, detail-oriented and a wonderful team member. I am very much looking forward to continuing to mentor her on this project and helping her grow into a leader of her own lab one day.”
Kugel’s lab has identified two versions of a highly lethal form of pancreatic cancer called pancreatic ductal adenocarcinoma — classical and basal — which are defined by a signature mix of genes that help the tumors form, survive and progress.
“The basal subtype tends to be even more aggressive and has the worst overall prognosis,” Wallace-Povirk said.
It’s also the rarer of the two, occurring in 30 percent of PDA cases, which makes it more difficult to study.
For example, it’s unclear what flips a classical state into the deadlier basal state, making it difficult to predict the path a tumor will take.
That’s what Wallace-Povirk wants to figure out with her F32 fellowship.
“By deciphering these biological differences, we can then figure out which drugs may target one subtype over another,” Wallace-Povirk said.
She also wants to anticipate how the cancer might defend itself against a drug by artificially accelerating that process in the lab.
“If we make them resistant, what biological processes change? What do they become sensitive to?”
By figuring out the disease’s likely next move, they can counter it with a move of their own.
“You’re always playing chess with cancer,” she said.
Wallace-Povirk said the F32 grant will help her achieve her goal of becoming a principal investigator. “Obtaining this award demonstrates the ability to articulate both a scientific project and career goal which are evaluated by NIH study section.”
Finding out what makes a quality kinetochore
Meanwhile in the Basic Sciences Division, Frank will use his F32 fellowship to study two ways that a key regulatory protein called ubiquitin provides quality control when cells divide.
Before one cell becomes two cells, it must make an exact copy of its chromosomes, line the pairs along the middle and pull the pairs apart so that each daughter cell gets its own complete set.
When it’s time to split, the cells assemble enormous, multi-molecular machines on each chromosome pair called kinetochores, which provide a platform for thin protein threads called microtubules to latch on to each half of the chromosome pair from opposite directions. The microtubules then tug the two chromosome halves apart and guide each one to opposite ends where new cells will form around them.
If the process goes wrong and daughter cells end up with too many or too few chromosomes, they may turn cancerous.
Kinetochores have an inner ring that binds to DNA and an outer ring that provides the platform for microtubules to grab on and pull apart. Frank’s project focuses on how ubiquitin, which typically tags defective and outdated proteins for destruction, plays a quality control role in the assembly of the kinetochore’s outer ring.
“It’s a pretty complex system that has to be built every single cell cycle,” Frank said. “So, you can look at it for its beauty that it works so well, but also there are a lot of opportunities for something to go wrong.”
Sue Biggins, PhD, who directs the Basic Sciences Division, is Frank's mentor and a leading expert in kinetochore biology. She studies how kinetochores work in budding yeast, an organism that shares much of its essential genetics with humans.
“Sue herself is a great mentor, and Fred Hutch has many mentoring opportunities and in general has a wealth of resources that people really look at and say this is a great training environment,” Frank said.
This was Frank’s first experience seeking outside funding for a project he designed himself.
“He completely switched fields when he joined my lab and has done a great job identifying key questions in the field and coming up with new ideas to tackle hard problems,” Biggins said. “He has already made substantial progress in his project, and I am really impressed with him. He had never written a fellowship application before, so it was great that he developed an entire NIH proposal on his own and got it funded with such a high score on the first pass.”
