Randy Carney, PhD: A visionary headed in new directions

Light particles

EHSC's 2020 Environmental Health Sciences Scholar is engineering new ways of seeing the world

Punta Molentis Italy
The Mediterranean coast off Punta Molentis, Italy, a likely sight on CV Raman’s journey home to India in 1921.

Before Randy, there was Raman

Like a poltergeist, a spectrum can describe the sudden appearance of a rainbow of colors in light after passing through a prism. In 1921, famed physicist CV Raman had been studying vibrations and sounds of instruments, like the Indian tambura and tabla, when a long boat trip across the Mediterranean got him thinking instead about waves of light.

Nearly a decade of experiments later and Raman would win the Nobel Prize in Physics for being the first to prove that the color of the sea came from water molecules scattering the sun’s light. The scattered light contained not only the original color but others that gave details about the water’s molecular structure. Raman’s discovery opened the door to a whole new field in physics analyzing the effects of light scattering through liquids.

A young CV Raman
CV Raman with his spectroscopy.

The Raman effect is the change in wavelength that occurs when molecules deflect beams of light. When light particles or photons hit liquid molecules, most of the energy and frequency of the wavelength that disperses stays the same. But sometimes molecules take or give energy to the photons and frequency changes.

To make precise calculations of light wavelengths, Raman invented a quartz spectrograph, which evolved over time to include new light sources and measurements. Today, Raman spectroscopy can monitor pharmaceutical manufacturing processes, give detailed information about nuclear waste, identify chemicals with a lifespan of one-trillionth of a second and biochemically predict the onset of life-threatening illnesses, to name a just few of its uses.

This year’s Environmental Health Sciences (EHS) Scholar Randy Carney is building an exciting, new generation of Raman spectroscopy and surface-enhanced Raman scattering (SERS) devices at his UC Davis lab in the School of Biomedical Engineering. Science writer Jennifer Biddle interviewed Dr. Carney to learn more about his research and what he hopes to get out of being this year's scholar.

How did you become an EHS Scholar?

I met Professor Sascha Nicklisch from the Department of Environmental Toxicology through some new faculty events – we were both hired around the Fall of 2018. Sascha and I began talking about our research interests. He quickly identified some of the tools and approaches my lab was developing that could be applied to probe new areas relevant to environmental health sciences.

Sascha nominated me for the EHS Scholar Award and helped develop my ideas along the way, and continues to do so. During the process of putting together my application for the award, it was exciting to learn about long-standing problems in environmental health that I could help to solve.

After some initial brainstorming, I focused in on detection of small molecule pollutants that are negatively impacting human health across the spectrum.

What was it like to win?

I was very excited to be selected for this honor. Historically, my training and research thrusts have been firmly in the fields of nanomaterials, engineering and chemistry, ultimately trying to develop better platforms to detect and diagnose cancer earlier than is currently possible. I wasn’t sure how useful a panel of environmental health experts would find my proposed ideas. Being selected was an affirmation that my ideas weren’t too naïve.

“It’s an interesting paradigm that occasionally good ideas and directions can come from not having direct expertise. It’s one of my favorite aspects of doing science, when new projects emerge from a clash of interests.”

What will you do during your tenure? How do you think it’ll help with your research and career?

My goal is to learn. UC Davis is renowned for its environmental health research, so I see this award as an opportunity to get my foot in the door and take advantage of the broad expertise.

After winning, the first thing we did was set up a mentoring committee with three outstanding women: Pamela Lein, Laura Van Winkle, and Christina Davis. They each are extremely accomplished and knowledgeable in carrying out and guiding research in environmental health sciences. I’ll be participating in EHSC’s activities, and listening carefully to the experts describe where their current methods are falling short.

By the end of the year, I’d like to be developing advanced, environmentally-centric research proposals for the National Institutes of Health. I also hope to forge new collaborations for my research group.

In the long term, I hope this experience opens up new funding directions enabling my lab to grow and continue carrying out cutting-edge research that makes a difference in my community. There are a lot of environmental health issues in Northern California that have piqued my interest, such as the horrific health burden on first responders to wildfires. Through my mentoring team, I hope to quickly learn about the specific areas that I can jump in and offer something new.

“It’s easy to get caught up in your own research niche, but refreshing to peek out and see a wider world of scientific pursuits.”

Detailed components of a single cell
Components of a cell: A single cell contains the basic building blocks of living things.
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Your research focus is on nanoparticles. Can you explain what they are to someone who isn’t familiar?

It’s mind-blowing to imagine how small the nanoscale truly is. I think we all can sort of picture how small a single cell is, which is already so tiny that you can’t see it with the naked eye. But if a single cell was blown up to the size of a professional sports stadium, a nanoparticle may be the size of the ball that the teams are playing with. But they could also be as big as the size of the bus the team travels on. So in and of themselves, they are very heterogenous in size, shape, composition and function, but they all have one thing in common: They are extremely small!

“Nanoparticles can operate like ultra-bright flares, to indicate the presence of a pollutant or pathogen, or to localize something of interest in the body when viewed from the outside.”

At this scale you start to approach the size of single molecules, but not quite. They have applications then in carrying around molecules, for example as a vehicle to deliver drugs to targeted cells. They are quite versatile little buggers, with near endless applications!

Give me the broad strokes of your research so far. What’s it about? What are its main goals?

Virus destroyed by nanoparticles
Nanoparticles destroying a virus.

Something that captivated me when I first began to learn about nanomaterials, a fact that emerged in the past century, is that they behave differently from their bulk counterparts. For example, imagine that you take a large chunk of gold and begin hacking it up, over and over and over. At some point, when you get small enough, the gold all of a sudden takes on entirely new properties. One is that they begin to interact with light in a very special way, cooperatively acting as a sort of pump, taking in photons, and generating intense electric fields, almost like an atmosphere around a planet. The surface of the nanoparticle essentially becomes a concentrated area of enhancement. That’s the first puzzle piece.

Quite separate from this nanoparticle-light story is a different light-mediated phenomena that happens at a molecular level. We don’t think about it too much, but all of our molecules, and the ones that make up the world around us, are constantly and consistently wiggling around, vibrating and rotating. Water for example, features particular wiggles and waggles between its hydrogen and oxygen atoms. Same for carbon dioxide, for sugar, for your DNA, and on and on. When light shines on these molecules, like the sun hitting an ocean, the light can change after passing through. The molecular wiggles may steal some of its energy. If we know the energy of the light before it hits the molecule, and then measure how much it lost after it bounces off, we can know exactly what that molecule is. This photon that changed its energy is called a Raman scattered photon, and it is extremely difficult to measure, a very rare process. That’s the second puzzle piece.

Now, if we combine the two puzzle pieces, we see something new. Any molecule waggling in this intense enhanced area at the surface of a nanoparticle essentially appears to be millions of times more numerous than it actually is! This is called surface enhanced Raman spectroscopy, or SERS, and it permits exceedingly sensitive measurements of any group of molecules.

My lab builds new platforms to use SERS to detect tiny molecular signatures of cancer that are so infrequent you can’t find them by conventional imaging, like ultrasound or CT scans. Thinking about the environment, SERS can be used to detect pollutants, pesticides and many other pertinent pathogens or bad players that may otherwise go undetected. 

What are extracellular vesicles or EVs? How are they ideal in detecting cancer?

Our bodies are actually nanomaterial engineering experts. Each of our cells, even right now, are releasing millions of small nanoparticles called extracellular vesicles, or EVs, that are made up of lipids, proteins, genes, and more. They get pumped around our body to other cells like letters to a long lost friend.

“If SERS is our flashlight, then extracellular vesicles are what we’re searching for in the dark.”

T-cell attacking a cancer cell
T cell (in blue) attacking a cancer cell.

In the past few years, we’ve realized that not all of this communication is to our benefit. A long list of nefarious biological problems can hijack this nano-highway. Cancer cells, virus-infected cells, cells that are dying from exposure to pollutants, and more, release EVs that are molecularly different from the normal ones.

Often these bad EVs can then perpetuate more problems, for example in cancer we know that they can go to other sites in the body to instigate metastasis and repel the normal immune cells that work to scout and monitor such bad behavior. Metastasis is a definitive step in the progression of cancer that makes it nearly impossible to treat without extreme intervention, and even then it can be futile.

The main direction of my young research lab is to use SERS to detect and analyze bad EVs among the normal healthy ones in very small volumes of biofluids collected from humans. EVs are more numerous, circulate longer in the blood, and are packed with more diagnostic information than typical biomarkers currently used.

We hope that in the future our work will translate to the development of new devices that can quickly and efficiently alert a physician to the onset of cancer in a timeframe where it’s still treatable.

What other possible applications could your research have in environmental health sciences?

One exciting possibility is that EVs or related nanoscale particles could also be trafficking some nasty persistent pollutants throughout our bodies. One of my early goals with respect to new environmental directions for the lab is to investigate this.

“Study of EVs themselves released as a consequence of exposure to environmental factors may illuminate a new understanding of disease progression and identify new targets for treatment."

More broadly, our SERS tools may improve detection of pollutants in the body without extensive purification of samples that is currently required. SERS can “see through” the rest of the molecules in blood, for example, to directly sniff out molecules of interest.

Have you always been interested in environmental health sciences?

My interest in environmental health has emerged over the past few years, primarily upon moving to California. The wildfires here are something I hadn’t experienced before. It’s clear that a heavy burden of toxic inhalation falls on our outstanding first responders and to us to try to learn more about these issues.

I feel a great responsibility to try to help. I hope that our tools can provide insight into the short- and long-term effects of inhalation of toxic combusted materials and affect positive change for this population.

And I want to learn more about issues in environmental health that aren’t even on my radar yet. I can’t overstate how excited my research team is to investigate new issues at the intersection of our lab’s tools and UC Davis’s expertise in environmental health.

If there’s one thing you could accomplish in your career, what do you hope it will be?

To me, more so than any particular new discovery, I see the pursuit of science as a cooperative undertaking spanning generations, from teacher to student to teacher. While I certainly hope and expect to unlock new discoveries that contribute to improving human health, my ultimate goal is to mentor the next generation of thinkers. I want to establish a legacy of inspiring future students to study, teach and practice science.

“While I hope to unlock new discoveries that contribute to improving human health, my ultimate goal is to mentor the next generation of thinkers.”