The Impact of Funding Cuts on Quackenbush’s Lab

The troubles began for Quackenbush and his laboratory earlier this year when the Trump administration started implementing significant budget cuts that affected research programs nationwide.

His lab is among the many struggling to survive in this harsh environment. With looming further reductions to the National Institutes of Health (NIH) funding, universities have been forced to lay off support staff, minimize hiring, and bring in fewer graduate students and fellows.

For years, Quackenbush’s lab has been pivotal in human genetics research and bioinformatics. The analytical tools created there assist scientists in understanding gene control mechanisms and the role they play in various diseases, from cancer to autism. Kenneth Ramos, a cancer researcher at Texas A&M Health, emphasized that many of the top labs globally often partner with Quackenbush. This year alone, his work has received a remarkable 100,000 citations.

“John has been one of the most impactful bioinformaticians in genomics for the past 25 years,” Ramos noted. “He has made many of the resources he developed publicly available, and he possesses an admirable curiosity and depth in exploring scientific inquiries.”

Quackenbush somewhat anticipated difficulties. Following Trump’s election, he opted to halt the recruitment of new trainees. He felt the threat to biomedical research and wanted to stretch his existing resources as far as possible. “I held back, trying to be cautious, not knowing what would happen,” he recalled. But now, unfortunately, most of the funding has vanished.

A significant loss occurred in April when Quackenbush, like many scientists over the past year, found that a key research program was terminated. He had applied for a renewal grant focusing on sex and gender differences in medicine, but communication issues delayed the review process. On April 4, the program was officially discontinued due to it “no longer aligning with administration priorities,” a phrase that has become all too familiar in the research community.

Additionally, the National Cancer Institute (NCI) discontinued its Outstanding Investigator Award program, which had been a vital funding source for Quackenbush, contributing towards his salary. While ongoing awards will continue to provide funding, Quackenbush’s was set to expire in 2025, and he had anticipated a renewal based on previous positive reviews.

“That was devastating. Then, while flying over Lake Michigan, I received news about mass grant terminations at Harvard. It was a moment filled with visceral fear and anxiety,” he shared.

Due to the freeze on grants at Harvard, he missed the chance to apply for a no-cost extension, which would have allowed him to use the remaining funds more effectively. After the freeze was lifted, he did receive the extension, but the reality is that hiring has turned from a choice into a dire necessity. As students graduate and postdoctoral researchers leave for other roles, he lacks the funds to replace them. The once-thriving research program he’d built at Harvard is now on the brink of collapse.

Most scientists in Quackenbush’s field see him as a methodology and computational tool expert. His lab developed a series of applications collectively known as the “Network Zoo,” which centers on machine learning tools that analyze gene regulatory networks, crucial for understanding how genes operate.

Quackenbush emphasizes that although all human cells share the same genome, what distinguishes them—like neurons and liver cells—are the differing sets of active genes. This realization has propelled his interest beyond just which genes are active, to a broader inquiry into the intricate relationships involving around 1,600 transcription factors, proteins that govern over 20,000 genes.

He explains the complexity: “These transcription factors regulate the timing and intensity of gene expression, activating numerous genes simultaneously to facilitate specific biological processes.”

Exploring these networks is vital for a fuller understanding of human biology and potential disease mechanisms. Yet, as Ramos pointed out, tools like those developed by Quackenbush are essential for modeling such intricate networks. Each application within the Network Zoo is whimsically named after an animal and serves different investigative purposes. A recent addition, PHOENIX, helps scientists track changes in gene networks over time and is the first model to encompass all 20,000 genes in the human genome, recognized by the NCI as a significant advancement.

Despite being a tool builder, Quackenbush maintains that his primary interest lies in using these tools to address scientific questions that intrigue him. For example, he and postdoc Tara Eicher initiated a study on genes tied to glioblastoma, an aggressive brain cancer, to see how they relate and if they explain outcome differences based on gender. “Tara took the idea and developed a method she calls BLOBFISH,” he mentioned, showcasing the creative methods they employ.

Eicher and Quackenbush have begun using this method in their glioblastoma research and are also applying it to study genes associated with autism.

All tools in the Network Zoo are open-source, allowing easy access for other researchers. Ramos noted, “Quackenbush has made bioinformatics accessible, enabling researchers with reasonable expertise to utilize these tools effectively.”

For instance, Ramos utilized a Network Zoo program to investigate overcoming drug resistance in cancer. Other researchers, like Dr. Dawn DeMeo at Brigham and Women’s Hospital, have also found value in these applications, particularly for exploring sex differences in lung diseases. DeMeo admitted earlier research seemed impossible without these tools.

She discovered significant regulatory differences between male and female gene expressions across various organ systems, which may help explain why women respond better to chemotherapy or why specific diseases manifest differently based on sex.

With grants that once sustained Quackenbush’s lab now either terminated or dwindling, sustaining these valuable tools is becoming increasingly difficult. Without the ability to hire new researchers, the momentum for developing new tools will inevitably stall. Quackenbush worries that the tools in the Network Zoo could deteriorate if not properly maintained, given the constant updates required for programming languages.

Over the past year, Quackenbush’s lab has seen a dramatic attrition—dropping from nine postdocs and graduate students to just three. Where there was once a bustling conference room for meetings, they now crowd into a modest office. While he hasn’t had to lay anyone off, Quackenbush expressed pride in the achievements of those who have moved on to other positions. However, the atmosphere among the remaining researchers has dimmed, with some attributing their departures to funding cuts and instability in the field.

Eicher, a postdoc, worries that her funding may run out soon, complicating her ability to juggle family responsibilities with job prospects abroad, even though many are considering opportunities in Europe due to current conditions.

“There’s discussion of moving to Europe among many,” Eicher noted. “But relocating my kids right now feels unmanageable.”

Staying at Harvard carries its own challenges. The School of Public Health, heavily reliant on grant funding, is tightening budgets, with significantly fewer Ph.D. students enrolled than usual and even the coffee in break rooms cut back. “It changes the environment a lot,” Eicher observed, indicating a stark reality of limited resources.

Considering the funding losses, Quackenbush has even thought about transferring to another university or exploring the creation of technology startups based on his work. “It’s been a wake-up call, making me aware of my resilient nature,” he stated. “I constantly seek ways to move forward.”

Reflections on a Challenging Path

Currently, Quackenbush still has a limited amount of funding to support his remaining team and maintain essential costs, but this is not a long-term solution. His lab has faced an estimated $1.2 million in losses this year, with potential cumulative losses of about $10 million in future years. Presently, he is relying on a handful of grants, including a subcontract that expires in May and additional funds from Amazon Web Services.

He has weighed opportunities from other institutions, such as offers from the University of Oxford, but has yet to make significant decisions. The financial terms haven’t rendered such a move feasible.

Quackenbush continues to manage dwindling lab finances by scouting for new opportunities. “I strive to find ways to keep progressing, despite everything,” he remarked.

This year, during a routine health check, he was confronted with mental health queries that starkly illustrated his current emotional state: “Are you feeling depressed? Yes. Anxious? Yes. Hopeless? Yes. It’s just such a tough time,” he recounted.

What weighs heavily on him is the perception gap between the scientific community and the general public or administration. “There’s a disconnect. We’re labeled ‘the elites’ at Harvard, used as political scapegoats. But the reality is, people genuinely care about research aimed at curing diseases,” he mused. “When you discuss day-to-day work, the response is always, ‘Yes, it’s significant.’”

Quackenbush’s roots trace back to a small town in Pennsylvania, raised by a single parent. He recalls a humbling upbringing where he worked as a dishwasher in a restaurant before being forced to step into a cooking role unexpectedly. Opting for college was a pivotal choice that ultimately made him the first in his family to earn a degree. Quackenbush transitioned from physics to genetics, establishing his lab in computational biology.

He expresses gratitude for the public investment in science, “As a scientist, I genuinely feel like the luckiest person in the world. I’ve had the privilege of pursuing interesting work, supported by taxpayers. My job is to repay that investment.”

Yet navigating these challenges is more daunting than ever. Securing large grants is becoming increasingly arduous, as private funding becomes scarce, and public grant applications can be extremely competitive and labor-intensive. The remaining funds are expected to diminish by next spring, and he admits, “I have no insight into what will follow.”

Despite the uncertainty, he remains committed to his research. “Every day, we come in, doing our best to tackle the current situation. We want to continue advancing our work,” he stated.

Even at a slower pace, Quackenbush insists they will persist until it becomes impossible to do so.