UChicago scientists tap the power of collaboration to address the biggest challenges

Modern biological and biomedical science are team sports, with primary investigators supported by a roster of students, postdocs, technicians, and administrators. Increasingly, scientists are also reaching outside the boundaries of their expertise, collaborating with partners from different disciplines who add their own skills, experience, and perspective to address the challenges of the rapidly changing modern world.

Addressing the health needs of a rapidly expanding and aging population; confronting climate change; making sense of the enormous troves of data generated by a networked world — these problems demand fresh thinking that couldn’t come from traditional research disciplines alone. The complexity and scale of such new scientific and engineering challenges also demand a diversity of perspectives and deep expertise that makes it increasingly difficult for any one scientist or laboratory to go it alone.

Instead, ambitious researchers look outward to expand the possibilities of their work and drive it toward impactful solutions. As these collaborations take shape, they form the foundations of entirely new, transdisciplinary fields and schools of thought. Gynecologists work with neuroscientists to restore sensation for breast cancer survivors. Cardiac surgeons and materials engineers build an ultra-thin pacemaker that is controlled by light. Marine biologists lend their expertise on microbes to help gastroenterologists treat digestive diseases.

“Biomedical research is at an inflection point where researchers who are driving discovery must adapt to meet the challenges and opportunities of a new digital era,” said Mark Anderson, MD, PhD, Dean of the Biological Sciences Division (BSD) and Pritzker School of Medicine, Executive Vice President for Medical Affairs, and Paul and Allene Russell Professor in the Department of Medicine at the University of Chicago. “To emerge as leaders in this rapidly changing environment, academic research institutions have to pivot to combine the deep domain knowledge of biological researchers and clinicians with the broader skillsets, methodologies and approaches to problem solving brought to the table by multidisciplinary teams of scientists and engineers.”

Transcending boundaries to maximize possibilities

Transcending institutional and disciplinary boundaries has been built into the fabric of the UChicago approach to science and engineering for decades. The University’s stewardship of national and affiliated laboratories, including Argonne National Laboratory, Fermilab, and the Marine Biological Laboratory, enables the development of new programs to accelerate research priorities. UChicago’s Hyde Park campus boasts a remarkable "built environment” where a major research university and health system benefit from proximity to highly ranked professional schools and humanities programs.  This unique research environment is surrounded by the Hyde Park neighborhood, which is home to many faculty, staff and learners, fostering serendipitous connections and a sense of rootedness in the community.

As the University considers its future, strategic growth, and ways to extract the most value from this wealth of intellectual capital, it is worthwhile to consider exemplary researchers who have already mastered the art of collaboration, and how others may emulate and leverage their success for even greater discoveries.

As a biochemist, Chuan He, PhD, is no stranger to this kind of field-shifting collaboration. With dual appointments as the John T. Wilson Distinguished Service Professor of Chemistry in the Physical Sciences Division (PSD) and Professor of Biochemistry and Molecular Biology in the BSD, he has been at the nexus of scientific innovation across UChicago.

“One of the great things about the University of Chicago is that everyone is accessible,” He said. “Graduates students and postdocs can just email and make an appointment with any of the faculty and talk about their science. I have realized that part is very critical. Whenever you encounter a biological problem and wonder if someone on campus has expertise, you can actually reach out to them.”

He is a pioneer in the field of epigenetics, which focuses on dynamic and reversible modifications of DNA that regulate how genes are expressed, influencing their activity without altering the underlying genetic code. These modifications to DNA act as molecular switches that determine whether a gene is turned on or off, thus influencing cellular processes, disease development, and overall organismal health.

In 2011 and 2012, He’s team developed new methods for mapping epigenetic markers that can silence or reactivate genes across an entire genome. These new tools are to the study of epigenetics what the microscope was to microbiology. With this knowledge, scientists can accurately examine epigenetic tags and begin to understand how they affect cellular characteristics and activity. He’s work in 2011 also helped initiate the new field of RNA modification research, or epitranscriptomics, which encompasses a similar range of mechanisms for regulating RNA molecules that carry out genetic instructions.

These testing methods and new biology open a world of possibilities for collaboration with translational clinicians and basic science researchers alike. In 2023, collaborators using these methods or working on RNA/DNA modifications with the He research group garnered an astonishing $18,327,451 in new federal and philanthropic funding. This work spans nine researchers across four different departments at UChicago and one from Northwestern, with projects involving multiple myeloma, ovarian cancer, population genetics, bioinformatics, and the role of environmental stress in cancer (another active grant pictured below with Ralph Weichselbaum was originally awarded in 2021).

He joined UChicago in 2002, working mostly as an inorganic chemist and partnering with microbiologists to study bacteria and pathogens. As his research pivoted towards human biology starting in 2008, he began to realize that collaborating with physicians, physician-scientists, and basic science researchers in the BSD would help him apply his unique skillset for the greatest impact.

“Human biology is obviously the most complex — and most thoroughly examined — system in terms of genetics, diseases, and health risk. So, if you want to learn basic biology, humans are an outstanding system to study,” he said. “We constantly learn from our collaborators, and when you partner with physician-scientists who also treat patients, there are opportunities where you will not only learn biology, but also hopefully develop clinically useful therapies or diagnostic tools. So, that’s been our philosophy, always thinking about how we can bring something unique to that partnership.”

An example of creative collaboration

He is a good example of creative and impactful collaboration across the University. While his work applies to many biological systems and diseases, his partnerships in cancer research perhaps provide the best demonstration of how such collaborations can impact human health:

Bissonnette worked with He to develop liquid biopsies that analyze epigenetic profiles in blood samples to detect colorectal cancer as a less invasive alternative to conventional colonoscopies.

As part of a metabolomics analysis, Chen used a single-stranded DNA sequencing technique invented by He’s team and discovered a nutrient found in meat and dairy products that improves the ability of immune cells to fight tumors (Fan, et al. Nature, 2023).

Chiu has worked with He on several projects and multiple grants to study multiple myeloma, including using liquid biopsies to evaluate response to treatment and using epigenetic modifications to understand myeloma risk disparities.

Cohn uses He’s DNA methylation assays to analyze patterns of epigenetic marks from neuroblastoma tumors (Applebaum, et al. JCO Precision Oncology, 2019) as a biomarker for survival rates in children. She has also used a second technology invented by He that can profile epigenetic tags on small amounts of DNA circulating in the blood (Applebaum, et al. Clinical Cancer Research, 2020) as a diagnostic tool to determine which patients will respond to standard therapy and who might need alternative approaches.

Yu-Ying He has worked with Chuan He on several projects investigating how environmental exposures to toxins can render cells more vulnerable to cancer. Their work includes a study on the role of epitranscriptomics in a skin cancer that develops from exposure to low levels of arsenic (Cui, et al. Nature Communications, 2021), and a $9.1 million R35 grant to examine how exposure to UVB radiation and arsenic affect how RNA methylation contributes to tumorigenesis in cancer.

A frequent collaborator with He, Weichselbaum studies epigenetic impacts on cancer immunotherapy and radiation treatments. The two have identified RNA modifications (Han, et al. Nature, 2019) that affect response to treatments (Wang, et al. Cancer Cell, 2023) and tested a drug molecule that can counteract these changes and improve patient outcomes.

“Chuan is just one example of how collaboration can expand your horizons as a scientist,” Anderson said. “We have many other faculty members taking advantage of our unique research community by engaging with partners across the university. I hope they can inspire others to do the same.”

Yu-Ying He said the payoff to these collaborations has been mutual and has greatly expanded the capabilities of her research group.

“Chuan is visionary and fun to collaborate with. During the past eight years, our group has been working with his lab closely to address the emerging question of environmental epitranscriptomics. In addition to performing a number of challenging RNA modification sequencing analyses and quantifications in his lab, he generously shared his conceptual insights with us,” she said.

“Collaborating with Chuan has dramatically sped up our project progression. Working with him also makes research exciting, as he is so passionate about science of epigenetics and epitranscriptomics. I look forward to continuing to collaborate with him.”

The freedom to make new connections

As scientists begin to apply their discoveries to myriad biological processes and systems, their research can spawn a web of scientific possibilities. Rather than one great scientist sitting at the center of a hub and spinning out individual spokes of independent research, this approach can build a network that connects previously unrelated fields through fundamental mechanisms of biology, disease pathology, physiological systems, and technologies.

Sometimes, these connections come about just by being in the right place at the right time. In an article from Medicine on the Midway, Cohn said she met He after attending one of his lectures.

“One of the things I love about the University is that I have this opportunity to interact with brilliant scientists. Shortly after attending Chuan's seminar, we met to discuss how we might be able to apply the new technology he developed to detect epigenetic marks in neuroblastoma,” she said.

For He, this variety and unpredictability comes by design. “I feel like if I can see what the next 10-20 years of my career is going to look like, that scares me,” he laughed. “Not everybody is this way, and there are plenty of people who work on things very deeply and thoroughly and make huge contributions to science. But I like to work on things where I can’t predict my future.”

Weichselbaum said He’s generosity and openness is helping him translate these discoveries to the beside and patient care.  “We not only have new biomarkers for cancer, but we also have strategies for intervention based on collaborations with partners like Chuan in the Department of Chemistry and the Physical Sciences Division. I’m very excited about it,” he said in a press release about one of their collaborations.

This branching network of possibility has led to a discovery that is potentially even bigger than detecting cancer or enhancing radiation treatment: boosting the world’s food supply. In 2021, He’s team published a groundbreaking study showing that by inserting a gene that affects RNA modification into rice, the plants grew three times more rice in the lab — and 50% more rice in the field (Yu, et al, Nature Biotechnology, 2021). The rice plants also grew longer roots, were better able to withstand stress from drought, and photosynthesized more efficiently. Additional experiments in potato plants yielded similar results.

Now He is the director of the Pritzker Plant Biology Center, a new space funded by a $10 million gift from the Margot and Tom Pritzker Foundation. The center will expand his RNA modification work and the research of other scientists searching for innovative ways to promote plant growth and resilience and increase crop yield.

This foray into plant biology represents a new direction for He’s research, but it’s also the next step in the natural progression of his stated philosophy to seek out projects where he can make the biggest impact. He offered advice for other scientists hoping to do the same.

“You have to be open minded, planning to reinvent yourself every five to seven years, and willing to get out of your comfort zone and go after something high risk,” he said. “Once you have the mindset that you are willing to share your expertise and you’re sincere about working as a team, then those projects will move forward. It doesn’t mean everything you do is going to work out, but even if just 10% of it leads to groundbreaking new discoveries, that’s totally worth it.”

He's career path may be unique to his skillset and temperament, but other faculty can travel their own, similar path by embracing the same underlying principles of open-minded collaboration. For researchers willing to push their boundaries, tapping into the interdisciplinary community and generous culture of cooperation already in place at UChicago can help tackle the biggest challenges of our time.