“The elements are like the alphabet of life. The language of life is created from the right combination of letters or characters.”
This is how chemistry professor Chris Chang sees chemical biology, as he said in an interview with The Daily Princetonian.
Chang joined the Princeton chemistry department in 2024. His group “studies the chemistry and biology of the elements … by drawing from core disciplines of inorganic, organic, and biological chemistry.”
A central research focus of Chang’s lab is understanding the essential roles that metal nutrients like copper, iron, and zinc play in biology. These metals are crucial for cell function across all kingdoms of life, from single-cell bacteria to complex organisms like humans. In particular, Chang is researching the evolutionary implications of the metal nutrients and how they have shaped biological behavior and complex processes like sleep, growth, and cell development.
“We use small molecules that specifically detect copper in its +1 oxidation state. These allow us to pinpoint which cells or organelles have higher copper levels, which is important since various diseases are tied to imbalances in copper,” said Gen Li, a postdoctoral researcher who works with copper sensing tools in Chang’s lab.
Li explained that in addition to neurological effects, excessive copper levels can trigger apoptosis — cell death — of healthy cells, which is part of why understanding where and how copper builds up is so important.
Aidan Pezacki GS described that the group visualizes the effects of copper on cells using analytical methods such as fluorescence microscopy. According to Pezacki, the sensors they develop “bind to copper ions inside cells and increase in brightness, allowing us to visualize copper dynamics using microscopy.”
Chang’s lab has explored how copper impacts the brain, specifically in the locus coeruleus, a region which is important for regulating sleep, attention, and arousal. This project is part of a larger effort to understand the molecular origins of sleep, including the evolutionary history behind different sleep stages like REM and non-REM sleep, which emerged as life transitioned from water to land.
“If you look at water-dwelling organisms, they don’t have REM sleep, but as organisms evolved to come on land, that’s when REM sleep started to emerge,” Chang told the ‘Prince.’
Copper also plays a role in synaptic plasticity, the brain’s ability to adapt and form memories. However, maintaining the right balance of copper is crucial as both a deficiency and an overload can impair brain function. Chang’s research on copper aims to unlock new insights into sleep disorders and neurodegenerative diseases.
“Copper is one of those metals that has both a biological and a chemical impact,” Chang explained. “It’s not just about the metal itself, but how it influences systems and processes that are fundamental to life.”
Chang’s research also extends to the broader topic of how metal nutrients influence cell survival and death. His lab is studying the role of these metals in diseases like cancer, neurodegeneration, and obesity, where there is often an imbalance in cell growth. By understanding how metals affect cellular decisions, Chang hopes to uncover new insights into the mechanisms of disease and develop potential therapeutic strategies.
“We found that certain lung cancer cells with mutations had lower levels of bioavailable copper,” Aidan said. “When we treated those cells with a copper chelator, they were more likely to die — suggesting a potential strategy for targeting cancers based on their metal metabolism.”
Chelators are compounds that can bond to a metal through two different points on the molecule, forming a ring complex with a metal center.
This connection between chemistry and real-world impact echoes Chang’s broader scientific path. Before beginning his research in chemical biology, Chang focused on renewable energy and sustainability throughout his Ph.D., specifically in carbon utilization. His interest in how elements cycle through the environment expanded to include other elements in the periodic table, particularly metals.
“Health and sustainability aren’t separate — they are intertwined,” Chang said. “We concentrate elements in our bodies just as the Earth cycles them. Whether it’s energy production or human health, chemistry is the link."
Chang envisions a future where chemistry continues to play a central role in unraveling the complexities of biology and medicine. He explained how the field of chemical biology has exploded in recent years, particularly in its implications on other fields like biology, physics, and engineering.
“It’s all chemistry, and it’s all interconnected. Whether you’re studying how elements cycle through the environment or how they affect life on a molecular level, everything comes back to understanding how these elements shape life.”
Aanya Kasera is an assistant Podcast editor who also writes about research for the ‘Prince.’
Please send any corrections to corrections[at]dailyprincetonian.com.
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