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Postdoctoral student Chris Shoemaker of the Denic Lab, who previously won a fellowship from the Damon Runyon Cancer Research Foundation, has now won the Pathway to Independence (K99) Award from the National Institutes of Health (NIH). This new fellowship will cover two more years of training for Shoemaker, whose research has taken him in an unexpected direction.

“I’m making a large switch from yeast and biochemistry to mammalian cells and genomics,” said Shoemaker. “The hope is that I can merge these interests into a new, more impactful research program.”

Shoemaker came to the Denic Lab in 2012 after earning his Ph.D in molecular biology and genetics at Johns Hopkins University, under the guidance of Professor Rachel Green. While working in the Denic Lab, Shoemaker was trained in yeast genetics and cell extract-based reconstitutions.

“Before Chris came to my lab, we only worked on budding yeast cell biology,” said Professor Vlad Denic. “He single-handedly spearheaded us into the brave new world that is genetic screening of somatic mammalian cells using CRISPR/Cas9 technology. I can now see a whole other future of scientific pursuits in my lab that would have remained inaccessible to us before him.”

Shoemaker used his new skills to study autophagy, or the controlled destruction of useless or defective cellular components. In his application for the K99 award, he described how the cell extract techniques learned in the Denic Lab were ideal for studying a process like autophagy, “where the reconstituted, de novo formation of an organelle is difficult to imagine without the full complement of factors and organellar precursors available in extract.”

“I came to (autophagy) several years ago, before the Nobel prize was awarded for it this year,” said Shoemaker. “It’s an incredibly complex, but shockingly poorly understood, process. It has something for everyone – protein quality control, organelle biogenesis, vesicular trafficking, and significant disease implications.”

Shoemaker made some strides in autophagy research while working with yeast in the Denic Lab. For example, in an August 2015 paper for Molecular Cell, Shoemaker, fellow postdoc Roarke Kamber, and Professor Denic discussed the role of Atg1 kinase during selective autophagy – an important regulatory process for non-dividing cells. Their research was based on techniques developed in the lab for performing cell-free assays on Atg1-mediated phosphorylation.

However, in order to pursue his new research interests, Shoemaker decided that he had to transition from yeast to mammals. Since this decision was made relatively late in his academic career, the K99 fellowship offered an ideal way to transition without losing momentum.

“These fellowships enable me to gain a unique combination of training that I otherwise would not be able to accomplish,” said Shoemaker. “It’s very rare for a postdoc so senior to be allowed to completely pivot into new scientific territory with the full force of the scientific community behind them. Normally when you try to switch areas of expertise the money dries up. In the case of the K99 it is the exact opposite. These fellowships have opened doors with regards to new fields, training and collaborators that would not have been possible otherwise.”

As with many fellowships, the K99 requires a mentoring component. In his application, Shoemaker describes a network of faculty who he plans to turn to for training and career development advice, including Dr. J. Wade Harper, Dr. Kevin Eggan, and Dr. Andrew Murray of Harvard, and Dr. Forest White of MIT. Shoemaker is also excited to become a mentor himself, and plans to take mentor training workshops and work with undergraduates through Harvard’s Systems Biology Summer Internship Program.

In his application materials, Shoemaker describes his ambition to get an independent faculty position that will allow him to pursue his research while guiding a new group of graduate students through their own academic careers. While he is passionate about continuing his work with autophagy, he is also eager to become a mentor and to establish a tone of cooperative, skillful intellectual rigor in his own lab.

“Don’t let his pleasant Midwestern demeanor fool you,” said Denic. “He is experimentally more aggressive than a NYC cabbie at rush hour.”

Before that happens, Shoemaker will use the K99 award to gain experience with mammalian genome editing in Harvard’s Eggan Lab, CRISPR screening at the Weissman Lab at the University of California, San Francisco, and confocal microscopy with the O’Shea Lab at Harvard. When he is confident in his skills and has earned a faculty position, Shoemaker plans to start building a promising team of students to continue probing the intricacies of autophagy.

“One person can only do so much – I’m excited to build and train a team that can really power through some of these questions and hopefully plug some of the gaping mechanistic holes that still exist,” Shoemaker said.

Author: Lindsay Brownell