Blog

Research at the University of Wisconsin-Madison drives innovation, saves lives, creates jobs, supports small businesses, and fuels the industries that keep America competitive and secure. It makes the U.S.-and Wisconsin-stronger. Federal funding for research is a high-return investment that’s worth fighting for. Learn more about the impact of UW-Madison’s federally funded research and how you can help.

Lingjun Li, a professor in the University of Wisconsin-Madison School of Pharmacy and Department of Chemistry, has spent decades developing powerful new ways to measure and map the molecular machinery of life.

Recently, Li and her collaborators at UW-Madison and the Howard Hughes Medical Institute introduced a new imaging technology that has the power to reveal biomolecular detail in tissues like cancer tumors in their native environments and at unprecedented resolution. That technology, recently reported in Nature Methods, has been described as a potential game-changer for biomedical researchers.

Li’s track record for advancing mass spectrometry and other techniques earned her a spot on The Analytical Scientist’s 2024 Power List, and she recently received a Kellett Mid-Career Award from the UW-Madison Office of the Vice Chancellor for Research. The award honors mid-career tenured faculty who have made key research contributions in their field.

Here, Li reflects on her lab’s interdisciplinary research, the importance of spatial molecular imaging, and how tools like AI and mass spectrometry are shaping the future of biomedical science.

Can you describe your research background and what brought you to UW-Madison?

I’m a bioanalytical chemist by training – my background is in analytical and biomolecular chemistry. I did a unique postdoc, spending a year at Pacific Northwest National Lab working on high-end mass spectrometry-based proteomics, and another year at Brandeis University in a neurobiology lab using crabs and lobsters as model organisms. I joined UW-Madison in December 2002 to combine mass spectrometry technology development with fundamental neuroscience research, always with the goal of improving human health.

How has your lab’s focus evolved since then?

Initially, we aimed to discover nervous system biomolecules called neuropeptides and understand their function. Over time, we’ve expanded to studying a wide variety of biomolecules – proteins, peptides, lipids, metabolites, glycans – and their spatial distributions in tissues. Mass spectrometry allows us to look at all of these molecules with high specificity. A major focus now is understanding how these molecules contribute to diseases like Alzheimer’s, work that we’re doing in collaboration with the Wisconsin Alzheimer’s Disease Research Center.

What makes mass spectrometry a powerful tool for your work?

Mass spectrometry measures the mass of molecules and can provide structural information about them. For proteins, we can determine amino acid sequences and their modifications. For lipids and metabolites, we can distinguish structural isomers – molecules with the same mass but different chemical bonds. That structural detail can be crucial, for example, in distinguishing cancer cells from healthy cells.

What’s the significance of spatial context in molecular imaging?

Cells, even adjacent neurons, can use different chemical messengers. Without spatial information, you lose context about how molecules function in specific areas. In cancer, for instance, being able to see tumor heterogeneity at a fine level could influence treatment strategies. That’s why we’re focused on imaging techniques that retain spatial resolution.

Your lab recently helped develop a new mass spectrometry imaging technique that’s been described as a game-changer. What’s new about it?

We integrated tissue expansion microscopy with mass spectrometry imaging. Traditional imaging mass spectrometry lacks spatial resolution and loses the important context of how molecules behave in their natural environment within tissue. By physically expanding the tissue under mild conditions, we preserve its molecular composition and native structure while achieving higher resolution without needing fancy or expensive new hardware. That makes this approach, led by Hua Zhang in my lab, both powerful and accessible.

Why is making this new technique accessible important to you?

We want this to be open and available to biomedical researchers everywhere. Anyone with a commercial mass spectrometer can use the technique, and tissue expansion itself follows a straightforward protocol. What’s exciting is that you can achieve higher resolution without expensive new equipment or long acquisition times. That opens up mass spectrometry imaging to more biologists – helping them investigate molecular detail down to the single-cell level.

How do you see analytical science contributing to broader research and societal needs?

Analytical science is central to so many disciplines. It’s not just about supporting other research – it’s a science of measurement. Whether it’s environmental pollutants like PFAS or biomarkers in human disease, we need tools that are sensitive and precise. Mass spectrometry-based approaches are increasingly seen as foundational tools in biological discovery. Analytical science enables system-level investigations that not only uncover new biological mechanisms but also inspire the development of innovative hypotheses and transformative technologies.

How is your lab thinking about AI and machine learning in this space?

We’re generating huge volumes of data. Machine learning can help us translate these data into biological and clinical insights. We already use clustering and algorithmic tools for things like neuropeptide identification and single-cell analysis. Collaborating with statisticians and developing new software is key to managing this complexity. AI has great potential for biomarker discovery and predictive modeling in precision medicine.

What makes your lab environment unique?

We’re very interdisciplinary. My group includes students and postdocs from analytical chemistry, pharmaceutical sciences and biophysics. That diversity helps us tackle big, meaningful problems. And analytical science is very practical – it not only advances health-related research but also prepares our trainees for real-world careers in academia, industry and public health.

What motivates your continued focus on technology development?

Our goal is always to develop tools that can improve human health. We don’t build technology for its own sake – it’s always about enabling discovery. Whether it’s understanding disease mechanisms, identifying early biomarkers, or informing treatment strategies, analytical science has the potential to make a real difference.

The research that led to the new technology recently described in Nature Methods was supported in part by the National Institutes of Health (grants R01AG078794, R01DK071801, R01AG052324, P01CA250972 and DP1DK113644) and the U.S. Department of Agriculture (2018-67001-28266).

Ocean health is moving into a danger zone, with rampant human-caused carbon dioxide emissions having already pushed ocean acidification levels beyond safe limits in large swaths of the marine environment, according to a recent study. The new findings underline the urgent need to ramp up protection of the world’s oceans, while simultaneously slashing CO₂ emissions, say experts.

But from a scientific perspective, worsening ocean acidification is not an overly surprising finding, considering that carbon dioxide emissions remain high, says lead author Helen Findlay, a biological oceanographer at the Plymouth Marine Laboratory in the UK

Researchers have known for decades that humanity’s CO₂ emissions are being absorbed by seawater, triggering chemical reactions that release hydrogen ions, in turn reducing the abundance of carbonate ions. This ocean acidification process — which has escalated in tandem with atmospheric emissions — has implications for a large number of ocean-dwelling calcifying species that rely on calcium carbonate for their shells, with harm to those species potentially reverberating throughout marine ecosystems.

“We have really good data sets, and the data sets and this paper really just emphasise that we’re just watching the system crash.… [W]e need to be making real change now so that we don’t make things worse,” Findlay says.

“In my assessment, [this new paper] confirms what we’ve been expecting,” agrees Johan Rockström, director of the Potsdam Institute for Climate Impact Research in Germany, who was not involved in the current study. “[W]e are unfortunately moving beyond the safe boundary on ocean acidification.”

Rockström’s international team — known for their groundbreaking planetary boundary research — is working on an updated Planetary Health Check, due out in September. Last year’s inaugural report found ocean acidification on the cusp of transgression. But evidence from multiple sources is now pointing to this boundary being crossed, he says. “It’s too early to say conclusively, but I think this [new] paper is important in that context.”

Mounting evidence of worsening ocean acidification should trigger a “much more ambitious level of ocean protection,” along with rapid climate action, Rockström says. “When you add one additional stressor, like ocean acidification, you have an even stronger argument to protect [marine systems] because they’re getting weaker under the pressure of multiple stressors.”

“

For all efforts to protect the ocean, it would be beneficial to stop emissions. The way forward is… to stop CO₂ emissions, and then the natural systems over time, over a long time, will help us bring things back into balance.

Hans-Otto Pörtner, marine biologist, Alfred Wegener Institute

Acidification widespread, and runs deep

Findlay’s team found that four of seven ocean basins have crossed the planetary boundary for ocean acidification — with polar waters and ocean upwelling areas particularly affected.

They also found that this acidification picture becomes worse when one looks deep below the ocean’s surface. The authors found that 60 per cent of the world’s ocean has crossed the safe limit down to 200 meters (656 feet) depth, compared to 40 per cent of surface waters.

That’s concerning for marine life, Findlay says, as this part of the water column is where much of Earth’s marine biodiversity thrives.

Rockström and an international team of planetary boundary scientists working out of Sweden’s Stockholm Resilience Centre previously set the safe limit for ocean acidification at 20 per cent aragonite saturation (aragonite being a form of calcium carbonate). But Findlay and her team, after assessing the acidification tolerances of a wide range of species and inspecting regional data, propose a 10 per cent aragonite saturation safe limit to ensure functional integrity of ocean ecosystems.

Concerningly, that would push the crossing of the safe space back to 2000.

The researchers found that rising ocean acidification levels have already caused “significant declines” in habitat for some calcifying creatures. According to their study, tropical and subtropical coral reefs have lost 43 per cent of their suitable habitat. Polar pteropods, a free-swimming form of planktonic marine snail, and a key part of the food chain, have lost 61 per cent of their suitable habitat, while coastal bivalves have lost 13 per cent.

“It’s quite frustrating to now be at a point where we’re saying, well actually, if we wanted a really good system — to be healthy and safe [for] all these ecosystems — we need to have gone back and kept [ocean acidification] at year 2000 levels,” Findlay says.

However, experts emphasise that current levels of acidification are not an immediate death knell for ocean life. But they do note that these rising levels are greatly concerning when factoring in the bombardment of the world’s oceans by other stressors including climate change-induced marine heatwaves, declining ocean oxygen levels, eutrophication, and more direct anthropogenic impacts such as overfishing and pollution from far-ranging sources including microplastics and raw sewage.

We need to see ocean acidification “as a component of other challenges that can make things worse,” says Hans-Otto Pörtner, a marine biologist at Germany’s Alfred Wegener Institute, former co-chair of the Intergovernmental Panel on Climate Change (IPCC) Working Group II who wasn’t involved in the recent study.

He emphasises that the risks posed by interactions between acidification, heating and oxygen loss are all driven by human carbon emissions. “My more holistic view would be that the interaction of these three [factors], in terms of Earth history … have been a driver for evolutionary mass extinctions.”

“The findings are certainly concerning for coral reefs and bivalves and many other organisms that rely on calcium for their shells and their skeletons,” adds Helen Fox, a senior scientist at the Coral Reef Alliance, California, who wasn’t involved in the recent research. “Corals are already suffering from an onslaught of impacts. We are still in the midst of the fourth global bleaching event. So there has already been a lot of death and habitat loss from bleaching.”

Urgency for ocean protection

Globally, marine protection lags far behind land efforts, say conservationists. But there is building momentum on the back of the just-concluded 2025 UN Ocean Conference. In recent weeks, a raft of new Marine Protected Areas (MPAs) and ocean protection commitments were announced, as nations moved toward ratifying the Agreement on Marine Biological Diversity of Areas beyond National Jurisdiction, also known as the High Seas Treaty.

This international agreement aims to push forward protection of 30 per cent of the world’s oceans by 2030 while establishing legal mechanisms for protection of high seas areas. Fifty countries have ratified the treaty so far, but 60 are needed for it to come into force.

Findlay says her team’s acidification findings should add impetus for nations who have yet to ratify the accord. “Any additional protection that’s placed on the ocean, provides an opportunity for ecosystem resilience against harder-to-solve issues, such as [ocean acidification],” she says. “However, [our findings] should also be a motivation to cut emissions, given that [acidification] and climate change are a [dual] threat to marine biodiversity, which this treaty aims to protect.”

In a June 2025 Nature commentary, Rockström and other scientists, including eminent marine biologist Sylvia Earle, warned that the high seas treaty, though important, will likely take years to put into action. They argue that urgent steps are needed immediately to protect the world’s oceans from all forms of exploitation.

“Given the urgency of addressing the climate and biodiversity crises, the world can’t wait another decade to fix the problems humans have created,” they write. “Ocean life is too precious and important to lose, and shifts in the chemical and physical environments of the sea, once made, will be irreversible on timescales of centuries to millennia.”

“For the high seas, 30 by 30 is not enough,” Rockström tells Mongabay. “We should halt 100 per cent of the high seas overexploitation with industrial fishing [and] industrial trawling and forbid all forms of deep-sea mining.”

Others say ocean protection must become far more adaptive in the face of rapidly changing ocean chemistry. That includes identifying and targeting conservation action in marine areas that could act as climate refugia for particularly vulnerable ecosystems.

“We talk about refugia in terms of heat. We do not talk about them in terms of other aspects, such as ocean chemistry, and we need to,” says Daniela Shmidt, a professor at the School of Earth Science at the University of Bristol, England, who wasn’t involved in the recent study. In-depth metrics on ocean acidification, warming and other marine changes could help identify key areas to protect, she adds. “We can’t protect all the world. So we need to know where our efforts are best placed.”

Addressing the root cause: Fossil fuels

All experts Mongabay interviewed for this story agree: The number one solution to address ocean acidification is to aggressively tackle its root cause — the continuing carbon emissions driving the uptake of CO₂ in the oceans.

Researchers recently warned that the window to keep warming below the 1.5°C (2.7°F) Paris Agreement target is rapidly closing, with only three years left. Several analyses have concluded that, barring a drastic course correction, the world is rushing toward a catastrophic 2-3°C (3.6-5.4°F) rise in temperature over preindustrial levels by 2100.

But even if atmospheric CO₂ levels were reduced today, the consequences of ocean acidification will remain with us for centuries as the oceans continue to soak up the CO₂ altering the sea chemistry and pH.

Experts stress that net zero and net negative approaches will be needed to protect oceans, including some geoengineering solutions that involve CO₂ removal (CDR) on land and sea — even though these technologies remain in their infancy, requiring much testing and scaling up.

Reducing ocean acidification will likely require novel methods, such as ocean alkalinity enhancement or electrochemical approaches. But these techniques come with still poorly understood consequences for marine life and ecosystems.

“We all know that reduction in CO₂ [emissions] is … the most important step. But maybe for some of the … really critical [marine] ecosystems, we might need additional adaptation or mitigation approaches,” says Nina Bednarsek, assistant professor of senior research at Oregon State University and a co-author on the recent paper.

CDR technologies will be necessary to a degree, agrees Rockström. “There’s not one climate scenario that you see that can hold 1.5° Celsius [2.7° Fahrenheit] and still giving us a little sliver of a remaining carbon budget for an orderly phase out of coal, oil and gas, without assuming very optimistic scaling of CDR.”

But he draws the line at more aggressive geoengineering approaches. “These are technologies that involve such a large-scale manipulation of the Earth system, with not well-understood and potentially catastrophic side effects, that they should, under all circumstances, be avoided,” he says. “Many of them will not even solve the problem, because [while] they could temporarily reduce the temperature, they wouldn’t get rid of the stress of acidification in the ocean.”

Pörtner is sceptical of geoengineering methods that add material to the ocean at a global scale, and instead emphasises the need to slash emissions and raise ocean protections. “For all efforts to protect the ocean, it would be beneficial to stop emissions,” he says. “The way forward is … to stop CO₂ emissions, and then the natural systems over time, over a long time, will help us bring things back into balance.”

“This doesn’t have to be all doom and gloom in terms of all ocean life … dying,” says Bednarsek. Instead, the passing of the safe threshold for ocean acidification should be viewed as an “early warning” spurring us to act. “This sort of knowledge is absolutely critical. It’s not just… to be alarmist. It’s … so we can do something about this.”

This story was published with permission from Mongabay.com.