Whitehead Institute researchers partner with Innovation Center scientists to move science forward

Whitehead Institute’s Innovation Centers—a collection of facilities each providing specialized expertise and technology in an area such as genomics, metabolomics, bioinformatics, or imaging—provide researchers with valuable research services. They conduct experiments or enable researchers to conduct experiments that might otherwise be outside the scope of what an individual trainee or lab could achieve. Trainees who work with the Innovation Centers soon learn that such services are not all the staff can provide; their deep expertise, institutional knowledge, and enthusiasm for research makes them potent collaborators and thought-partners.

Graduate student Pushkal Sharma, a researcher in Whitehead Institute Member Ankur Jain’s lab, learned this firsthand by working with Heather Keys, the director of the Functional Genomics Platform, one of the Institute’s Innovation Centers. Pushkal first went to Heather to get her help setting up a genomics experiment for a project. Years later, Heather has become a close collaborator, mentor, and friend. She is one of the first people Pushkal goes to when he wants to bounce ideas off of someone. Their collaboration proved especially fruitful in Pushkal’s most recent research project, for which Heather suggested an experiment that ended up providing a crucial clue.

“Heather’s insights were essential for getting this project done,” Pushkal says. “Her expertise means that she can come up with ideas for genomics experiments that you would never think of on your own.”

Heather has been at Whitehead Institute since 2007. She started as a graduate student in former Whitehead Institute Member David Sabatini’s lab and later took over the Functional Genomics Platform, which was in its infancy. The Center runs experiments that use CRISPR-based gene editing technology and other genomics approaches to find out what genes or pathways are important for different processes in a cell. The approach allows researchers to screen the entire genome at once, rather than testing genes one-by-one, to find connections between genes and cellular processes. This unbiased, large-scale approach can massively speed up research, or even make it feasible to ask research questions that otherwise would have been too expensive and time-consuming to attempt.

Pushkal first reached out to Heather early in his time at Whitehead Institute because he had a research question that required running a genome-wide search. Pushkal’s background is in chemical engineering, not biology, so he had not had much training in genetics. Heather takes teaching seriously, so when a trainee comes to her, she does not simply figure out what she needs in order to run an experiment for them. Instead, she teaches them how to do the experiment themselves. In Pushkal’s case, she made sure to discuss the relevant genetics background with him, as well as to work through the quirks of how to ensure that a CRISPR screen will provide good results. 

“I think that teaching trainees to do the experiments themselves is important, so that they’ll have the skills to do this sort of research if they end up running a lab somewhere that doesn’t have equivalent core facilities or research services,” Heather says. Pushkal agrees, saying that when the time came for him to run genetic screens for his recent project, he felt capable of doing almost every step by himself. When he consults with Heather now, they spend little time making sure he’s setting up his experiments correctly, and most of their time exchanging ideas about what research questions to ask and how best to answer them.

“Heather doesn’t just offer a research service. She sits down, tries to understand what you're trying to do, and offers advice like is this the right experiment to do? It’s not like you just drop off a sample and she runs it for you. She really tries to make sure you are doing the best science possible,” Pushkal says.

Heather sees her role as helping researchers to consider their projects from different angles. “The trainees are the experts in their areas, but when you work on one thing for a long time you can end up with tunnel vision. I think that's why it's important to talk to many different types of people, because they might have an insight on something that you haven't thought about or they might be seeing the data in a different way. That’s what I try to offer,” Heather says.

Heather also learns a lot from the researchers that she works with. Pushkal taught Heather about the subject of his research, small molecules called polyamines that are present in our cells in large quantities. Polyamines appear to be important for health, and yet researchers do not have a clear understanding of what they do in cells.

“Pushkal’s scientific question was very interesting to me, and it’s been really fun following along with his progress,” Heather says. “Also, although our different backgrounds made communication a little harder at the beginning—I had made some assumptions about his familiarity with genetics—once we worked through that, it became fascinating to learn from each other’s perspectives.”

Pushkal and Heather’s first collaboration was a success, and the work became a section within Pushkal’s 2025 paper on polyamines. In the paper, Pushkal described a tool he developed to measure the level of polyamines in cells, and then a series of experiments he did—including the gene screen with Heather—to learn more about what can change that level.

Researchers do not always keep Heather in the loop as they work on their papers. Science is a long process, and there can be years between the gene screen experiments that researchers do with Heather and the publication of a paper including that experiment. However, Pushkal stayed in touch. He says that Heather has become a great mentor.

“It’s really nice to have a mentor who has a lot of experience and a big picture view of the science, similar to a PI (the head of a lab), but who is also still running experiments, which most PIs are not,” Pushkal says. “Whenever I have any roadblock, like an experiment is not going as planned, Heather is one of my key people I ask for an opinion.”

Pushkal began inviting Heather to the Jain lab’s meetings, in which lab members share their research with the whole lab group. Now, other members of the lab also work with Heather and regularly invite her to lab meetings, where she can stay informed about what the lab members are working on and offer her perspective.

“Heather has become a great resource for members of my lab,” Ankur Jain says. “They hold her and her opinions in high esteem, and her involvement has benefited several projects.”

As Pushkal began working on a follow up to his first polyamine paper, he of course ran his ideas by Heather. This time, Pushkal wanted to figure out what polyamines actually do inside of cells. He had come up with five experiments to try to answer this question from different angles. Heather suggested a sixth experiment, which could identify what polyamines do by searching for genes that perform the same function.

Pushkal had not thought of that idea because, he says, “What is the probability that two cellular pathways are doing the exact same thing?” However, he trusted Heather and added the experiment to his list. When the six experiments were done, the one that returned the most promising results? The screen that Heather suggested. 

“My job is to help researchers get from point A to point B with the least amount of trouble,” Heather says. “People often come in thinking they know the quickest path from point A to B, and it’s my job to say: actually, that path is full of pitfalls or there’s a much better shortcut over here. I have a lot of experience of what works and doesn’t work with a screen, and so I use that knowledge to help them make strategic decisions.”

“Heather’s insight became really key to the whole project,” Pushkal says. “That experiment helped us figure out what we think is a new mechanism by which polyamines protect cells.” 

The experiment suggested that polyamines are involved in protecting cells from damage or death caused by the presence of iron. Cells need metals like iron, copper, and zinc for lots of different functions; for example, iron is essential to transport oxygen in blood cells. However, metals are highly reactive—think of copper oxidizing or iron rusting out in the world—and if metals react with other molecules in cells when they are not supposed to, this can cause serious dysfunction, damage, or cell death.

Guided by the clue from the gene screen, Pushkal conducted further experiments to see how polyamines interact with iron in cells. He found evidence that polyamines can form a sort of protective buffer that shields iron from undergoing damaging reactions.

Heather helped Pushkal to this discovery in more ways than one: after they collaborated on the screen that revealed the iron-pathway connection, Heather told Pushkal what other researchers she knew were working on related cellular pathways. Some of these researchers became important new collaborators for Pushkal.

For example, Heather suggested that Pushkal reach out to Whitney Henry, a Whitehead Institute alumna who is now a professor at the Koch Institute For Integrative Cancer Research at the Massachusetts Institute of Technology. Whitney studies how a form of cell death caused by iron could be used to kill cancer cells, and has developed extensive knowledge of how cells manage susceptibility to iron damage. When at Whitehead Institute, Whitney had worked with Heather on a screening project that led her to many of the discoveries she is building upon in her own lab.

“Whitney became crucial to this paper. We did many experiments in her lab, and I even attend her lab meeting,” Pushkal says. In this way, working with an Innovation Center member can be a gift that keeps on giving: not only did Pushkal receive experimental data for this specific project, but also valuable collaborations that could lead to future projects.

Pushkal believes these experiences demonstrate the value of the deep institutional knowledge of the Innovation Center staff.

“Heather knows everyone at the Institute and what they are working on,” Pushkal says. “She’s like a central node in this big network of researchers, and so she can make connections between people who could benefit from each other’s knowledge and resources.”

Pushkal’s follow-up paper is now out as a preprint, and he is beginning to look for his next opportunities after he completes his training at Whitehead Institute. As he gets closer to the end of his time at the Institute, he recalls his collaborations with Heather as having been valuable for both his research progress and his experience as a member of the Whitehead Institute community. 

“As a research trainee, you have to learn and accomplish a lot in a very limited time, and it would be impossible to do it on your own. The Innovation Centers are filled with great scientists who have decades of experience and expertise, and who are eager to collaborate to push your research forward,” Pushkal says. “I’ve learned so much from working with Heather, and we’ve also become friends. It’s nice to have another person at the Institute who I can talk to not just about science, but about life. If any new trainee is debating whether or not to reach out to an Innovation Center for help, I’d say: you should absolutely do it.”