Category Archives: Environmental and Molecular Toxicology

Giving therapy-resistant cancer cells a taste of their own medicine

The use of chemotherapy to fight various forms of cancer in the human body has been a successful method for decades, but what happens when it fails? This question strikes a personal note for Martin Pearce, a Ph.D. candidate in the Department of Environmental and Molecular Toxicology at Oregon state University. Prior to his graduate work, both of his grandmothers were diagnosed with breast cancer. One successfully went through treatment and although the other initially responded well to chemotherapy, years later the cancer cells reappeared and there was no other treatment available.

Martin in the lab, running one of many Western Blots.

The academic system in the United Kingdom, from where Martin hails, encourages undergraduate students to take what is termed a “placement year” between their second and third years to gain practical experience. At the time of his grandmother’s returning prognosis, Martin was in the second year of his studies at University of the West of England Bristol which had a connection with East Carolina University in the States. Although deviating somewhat from his initial advanced level courses in business, the opportunity to work full time in a biomedical sciences lab at a university renowned for its medical research provided just the right place for Martin to spend the following year.

Martin’s time in North Carolina was not only practical but a reminder of his experience with biology in secondary school. His teacher was a doctor and she encouraged him to pursue a career in a biomedical field. While biology wasn’t his easiest subject, Martin was inspired by his mentor and enjoyed the challenge. Today, he is fully committed to this challenge as a key member in Dr. Siva Kolluri’s Cancer Biology lab group at Oregon State University researching new strategies to target the cancer cells that continue to grow after treatment with chemotherapeutic agents.

Current members of Dr. Siva Kolluri’s Cancer Biology Laboratory group.

Their work involves screening tens of thousands of compounds against such resistant cancer cells that express a particular group of proteins called the Bcl-2 family of proteins. The lab has discovered a novel compound that binds specifically to the Bcl-2 family of proteins that are consistently expressed in therapy-resistant cancer cells and cause them to change shape. One of the fundamental principles of cell and molecular biology is the relationship between structure and function. Change the structure of a molecule and its function within a cell can completely transform. In the case of the Bcl-2 family of proteins, this literally means life or death for the cell.

Protected within the typical expression of a Bcl-2 protein is a region Martin describes as a “death domain”; if this domain is exposed, it induces cell death. Cell death or ‘apoptosis’ is a naturally occurring process in biology. Without apoptosis in the early stages of human development, we would all have webbed fingers! Martin and his team have discovered a compound capable of binding to a Bcl-2 protein, causing it to unfold and expose its death domain. Thus, the protein transforms from one that protects the resistant cancer cell into one that kills it.  

Example of Breast cancer cells that are resistant to chemotherapeutic agent Taxol, that are responsive to compound Bcl-2 Functional Converter (BFC). Blue dots are cancer cell colonies.

Demonstrating the effectiveness of this pathway at the cellular level is remarkable, but Martin explains even the years it has taken to reach this stage are just the beginning of a very long process until it can be used to treat people with cancer. Beyond discovery, through the work of his Ph.D. Martin has realized other critical steps in developing effective cancer treatments that occur outside of the lab. For example, once a compound has been identified that successfully binds to a target protein, medical researchers must work with a patent attorney to protect their work and generate funding. Without patent protection, new drugs can’t be developed.

The dedication to ‘translational research’ or science that is specifically designed to be applied in improving health outcomes is what drew Martin to work with Dr. Kolluri in the first place and continues to inspire his plans for the future. Drawing back to his early interest in business, after finishing his Ph.D., Martin intends to explore a career as a patent attorney.

“This way I can be involved in the most exciting part of the process for me and be a part of people being at the edge of achieving what I was initially inspired in this career to achieve.“

Lifelong Bristol City F.C. supporters, Martin and his dad at Ashton Gate Stadium.

To hear more about Martin’s graduate work and insights into translational research, tune in on Sunday, October 13th at 7 PM on KBVR 88.7 FM, live stream the show at http://www.orangemedianetwork.com/kbvr_fm/, or download our podcast on iTunes!

Zebrafish sentinels: studying the effects of cadmium on biology and behavior

Cadmium exposure is on the rise

There’s a good chance you might have touched cadmium today. A heavy metal semi-conductor used in industrial manufacturing, cadmium is found in batteries and in some types of solar panels. Fertilizers and soil also contain cadmium because it is present in small levels in the Earth’s crust. The amount of cadmium in the environment is increasing because of improper disposal of cell phone batteries, contaminating groundwater and soil. This is a problem that impacts people all over the world, particularly in developing countries.

Plants take up cadmium from the soil, which is how exposure through food can occur. Leafy greens like spinach and lettuce can contain high levels of cadmium. From the soil, cadmium can leach into groundwater, contaminating the water supply. Cadmium is also found in a variety of other foods, including chocolate, grains and shellfish, as well as drinking water.

Cadmium has a long half-life, reaching decades, which means that any cadmium you are exposed to will persist in your body for a long time. Once in the body, cadmium ends up in the eyes or can displace minerals with similar chemical properties, such as zinc, copper, iron, and calcium. Displacement can cause grave effects related to the metabolism of those minerals. Cadmium accumulation in the eyes is linked to age-related macular degeneration, and for people in the military and children, elevated cadmium is linked to psychosocial and neurological disorders.

Read more about cadmium in the food supply:



Using zebrafish to study the effects of cadmium

Delia Shelton, a National Science Foundation post-doctoral fellow in the Department of Environmental and Molecular Toxicology, uses zebrafish to investigate how cadmium exposure in an individual affects the behavior of the group. Exposing a few individuals to cadmium changes how the group interacts and modifies their response to novel stimuli and environmental landmarks, such as plants. For example, poor vision in a leader might lead a group closer to predators, resulting in the group being more vulnerable to predation.

Zebrafish

As part of her post-doctoral research, Delia is asking questions about animal behavior in groups: how does a zebrafish become a leader, how do sick zebrafish influence group behavior, and what are the traits of individuals occupying different social roles? These specific questions are born from larger inquiries about what factors lead to individual animals wielding inordinately large influence on a group’s social dynamic. Can we engineer groups that are resilient to anthropogenic influences on the environment and climate change?

Zebrafish

Zebrafish are commonly used in biomedical research because they share greater than 75% similarity with the human genome. Because zebrafish are closely related to humans, we can learn about human biology by studying biological processes in zebrafish. Zebrafish act as a monitoring system for studying the effects of compounds and pollution on development. It is possible to manipulate their vision, olfactory system, level of gene expression, size, and aggression level to study the effects of pollutants, drugs, or diseases. As an added benefit, zebrafish are small and adapt easily to lab conditions. Interestingly, zebrafish are transparent, so they are great for imaging. Zebrafish have the phenomenal ability to regenerate their fins, heart and brain. What has Delia found? Zebrafish exposed to cadmium are bolder and tend to be attracted more to novel stimuli, and they have heightened aggression.

Read more about zebrafish:

ZFIN- Zebrafish Information Network – https://zfin.org/
Zebrafish International Research Center in Eugene Or – http://zebrafish.org/home/guide.php



What led Delia to study cadmium toxicity in zebrafish?

As a child, Delia was fascinated by animals and wanted to understand why they do the things they do. As an undergrad, she enjoyed research and pursued internships at Merck pharmaceutical, a zoo consortium, and Indiana University where she worked with Siamese fighting fish. She became intrigued by social behavior, social roles, and leadership. Delia studied the effects of cadmium in grad school at Indiana University, and decided to delve into this area of research further.

Delia began her post-doctoral work after she finished her PhD in 2016. She was awarded an NSF Postdoctoral Fellowship to complete a tri-institute collaboration: Oregon State University, Leibniz Institute for Freshwater Ecology and Inland Fisheries in Berlin, Germany, and University of Windsor in Windsor, Ontario. She selected the advisors she wanted to work with by visiting labs and interviewing past students. She wanted to find advisors she would work well with and who would help her to accomplish her goals. Delia also outlined specific goals heading into her post-doc about what she wanted to accomplish: publish papers, identify collaborators, expand her funding portfolio, learn about research institutes, and figure out if she wanted to stay in academia.

Research commercialization and future endeavors

During her time at OSU, Delia developed a novel assay to screen multiple aspects of vision, and saw an opportunity to explore commercialization of the assay. She was awarded a grant through the NSF Innovation Corps and has worked closely with OSU Accelerator to pursue commercialization of her assay. Delia is now wrapping up her post-doc, and in the fall, she will begin a tenure track faculty position at University of Tennessee in the Department of Psychology, where she will be directing her lab, Environmental Psychology Innovation Center (E.P.I.C) and teaching! She is actively recruiting graduate students, postdocs, and other ethnusiatic individuals to join her at EPIC.

Please join us tonight as we speak with Delia about her research and navigation of the transition from PhD student to post-doc and onwards to faculty. We will be talking to her about her experience applying for the NSF Postdoctoral Fellowship, how she selected the labs she wanted to join as a post-doc, and her experience working and traveling in India to collect zebrafish samples.

Tune in to KBVR Corvallis 88.7 FM or stream the show live on Sunday, April 7th at 7 PM. You can also listen to the episode on our podcast.

Exploring the disconnect between humans and the ocean

Unseen associations

We are all connected to the ocean, and organisms living in the ocean are an integral – if often unseen – part of our lives. You might be more connected to the ocean than you think. For example, fertilizer used to grow vegetables is often made from fish, and ingredients derived from fish are often added to processed foods. And amazingly, the ocean produces more than half of the oxygen on the planet, while also being responsible for storing 50 times more carbon dioxide than is found in the atmosphere.

The impact of human activity can be observed in a variety of ways. Run-off from agriculture empties into fragile marine ecosystems, and plastic accumulates in the ocean and cycles back into our food supply, for example. Consequences of human activity disturb a precarious balance that is not fully understood. Within the American mind, there is a fractured connection to the ocean, and it is this disconnect that Samm Newton is studying. As a 3rd year Master’s student in the Environmental Arts and Humanities program in the College of Liberal Arts, she is exploring multiple questions as part of her thesis. What has been the role of science and technology in how we have known the ocean? What has been the relationship between that knowledge and how we have valued and made decisions about marine systems? And, how can scholars approach the study of these relationships in new ways?

Scientific inquiry is a tangled knot: the direction of research is often decided based on narrow criteria

Scientific funding agencies have often determined the direction of research based on the priorities of a moment in time. Some priorities arose from crises, while others might have been derived from a perceived risk to lives in human or animal communities. Other priorities were influenced by what types of technology and datasets were available. Within that structure, it has been difficult for science to be innovative if it doesn’t address a problem that has been classified as relevant by funding authorities. Samm explains further, “we have taken the environment, deconstructed its components, and focused only on certain aspects that we deemed interesting at a given moment, while the rest of the pieces slid into the background.”

Samm studies the ocean using methods traditionally associated with the humanities. She describes her method as an interdisciplinary approach to unpack how we have generated knowledge about the ocean through science. Her approach includes extracting information from scientific history and papers, archives, oral histories, as well as popular literature from sources like National Geographic and the Washington Post.

Different ways to think about our connection with the ocean

How can we encourage people to recognize their connection to the ocean, and direct their attention to how their lives are impacted by ocean issues? Samm indicates how advancements in technology and media have created new ways for people to access scientific knowledge about the ocean. With outlets such as Nautilus live, people can learn about ocean ecosystems by watching videos of organisms living in the sea. They can also interact with scientists in real time (check out this one about a large number of octopus brooding near Monterey Bay, CA. Science videos on the internet have become an engaging and popular way to share knowledge of the ocean and science with a broad audience.

“The ocean is very special to me.”

Samm grew up in the “shadow of the petrochemical industry” in Freeport, Texas, where the sea is brown, and air and water pollution are an everyday reality. Observing these anthropogenic forces impacting her coast and community, and how disconnected people seem to be from the ocean, led her to question the relationship between humans and marine environments. She found that science and technology have played a dominant role in how we have known the ocean—and possibly how we have valued it. Samm also found that methods from the humanities, particularly marine environmental history, as well as science and technology studies, provide a meaningful framework to examine that relationship further.

During her undergrad, Samm studied psychology and behavioral neuroendocrinology, with a focus toward consciousness and philosophy of the mind. She spent 10 years working outside of academia before pursuing a Master’s degree at OSU. Samm credits the Environmental Arts and Humanities program at OSU with providing a flexible framework for people from different backgrounds – including art and science – to decide how they want to study a topic of interest.

After finishing her Master’s degree, Samm plans to pursue a PhD in an interdisciplinary field studying environmental issues. As a graduate student at OSU, Samm has enjoyed working in a “scholarly space, and getting the opportunity to do research.” Beyond grad school, Samm’s goal is to be involved in work that transforms the world, and to contribute to projects that strengthen interdisciplinary associations between diverse, yet interconnected, academic fields.

Check out Samm’s exhibit at Autzen House on the OSU campus:The Need to Know Comes in Waves: Paintings by Samm Newton

On view from Sept. 20th – Dec. 15th, 10 AM – 4 PM at Autzen House (811 SW Jefferson)

Reception Oct. 18th, 4 – 6 PM; mini artist talks at 4:30 and 5:30

Samm will also be the Featured Artist at Hatfield Marine Science Center in Newport, OR in January 2019. Check out this page for more details!

When Fungus is Puzzling: A Glimpse into Natural Products Research

Ninety years ago, a fungal natural product was discovered that rocked the world of medicine: penicillin. Penicillin is still used today, but in the past ninety years, drug and chemical resistance have become a hot topic of concern not only in medicine, but also in agriculture. We are in desperate need of new chemical motifs for use in a wide range of biological applications. One way to find these new compounds is through natural products chemistry. Over 50% of drugs approved in the last ~30 years have been impacted by natural products research, being directly sourced from natural products or inspired by them.

Picture a flask full of microbe juice containing a complex mixture of hundreds or thousands of chemical compounds. Most of these chemicals are not useful to humans – in fact, useful compounds are exceedingly rare. Discovering new natural products, identifying their function, and isolating them from a complex mixture of other chemicals is like solving a puzzle. Donovon Adpressa, a 5th year PhD candidate in Chemistry working in the Sandra Loesgen lab, fortunately loves to solve puzzles.

Nuclear Magnetic Resonance (NMR): an instrument used to elucidate the structure of compounds.

Donovon’s thesis research involves isolating novel compounds from fungi. Novel compounds are identified using a combination of separation and analytical chemistry techniques. Experimentally, fungi can be manipulated into producing compounds they wouldn’t normally produce by altering what they’re fed. Fungi exposed to different treatments are split into groups and compared, to assess what kind of differences are occurring. By knocking out certain genes and analyzing their expression, it’s possible to determine how the compound was made. Once a new structure has been identified and isolated, Donovon moves on to another puzzle: does the structure have bioactivity, and in what setting would it be useful?

Donovon’s interest in chemistry sparked in community college. While planning to study Anthropology, he took a required chemistry course. Not only did he ace it, but he loved the material. The class featured a one-week lecture on organic chemistry and he thought, ‘I’m going to be an organic chemist.’ However, there were no research opportunities at the community college level, and he knew he would need research experience to continue in chemistry.

At Eastern Washington University, Donovon delved into undergraduate research, and got to work on a few different projects combining elements of medicinal and materials chemistry. While still an undergrad, Donovon had the opportunity to present his research at OSU, which provided an opportunity to meet faculty and see Corvallis. It all felt right and fell into place here at OSU.

As a lover of nature and hiking in the pacific northwest, Donovon has always had a soft spot for mycology. It was serendipitous that he ended up in a natural products lab doing exactly what interested him. Donovon’s next step is to work in the pharmaceutical industry, where he will get to solve puzzles for a living!

Tune in at 7pm on Sunday, March 18th to hear more about Donovon’s research and journey through graduate school. Not a local listener? Stream the show live.

A Big Punch at the Smallest Scale

How do you connect the dots between sunscreen, coatings on reading glasses, and medicine? Nanoparticles! More and more the potential uses of nanotechnology are moving forward. For example the use of nanoparticles in sunscreen (i.e. zinc dioxide) helps to increase its protective coverage time and its ability to block harmful UVA rays. Another emerging field of nanotechnology hopes to decrease the economic burdens of growing enough food for a booming world population. Matt Slattery joins us from the College of Agricultural Sciences Department of Environmental and Molecular Toxicology to discuss his flourishing endeavor to ensure that technology does not outpace environmental safety.

Matt reflecting at Panther Creek Falls

Matt reflecting at Panther Creek Falls.

Growing food takes a serious amount of commitment, time, and money; and one of the major factors dictating a successful harvest is the timing and effectiveness of the pesticides applied to a crop. Over a billion (1,000,000,000) lbs of the active ingredient in pesticides are applied in the USA alone (EPA)! With the help of nanotechnology we can decrease the necessity of repeated pesticide application and still get the same level of productivity from the land. When pesticides are applied, they generally have a very short residence time, and are only effective in fighting pests for a week or two. However, by encapsulating pesticides in multi-layered nanoparticles that slowly releases a small quantity of pesticide over time, you can get a far more consistent application instead of the boom-and-bust strategy that’s currently used. Another major benefit of nanoparticle delivered pesticides is that farm workers are less exposed to the chemicals because application of the pesticide is less frequent and safer. This encapsulation method is not just for an agricultural application but has the potential to be used in any platform that needs a “time-release” delivery, but much work is still required to make sure we really understand how they interact with the environment.

Matt having a grand time play his ukulele in Halong Bay, Vietnam

Matt having a grand time playing his ukulele in Halong Bay, Vietnam.

To no surprise, it takes someone special to merge multiple scientific disciplines into one research project, and our guest fits the bill! Matt has always been interested in science, but it was the interdisciplinary nature of environmental toxicology that requires the understanding of how chemistry, physics, and the environment can affect the biology and health of an organism. His first experience with the contamination of the Puget Sound in Bellingham, while attending Western Washington University, was a catalyst that launched him to eventually work with the Lummi Tribe. There he joined the discussion of how salmon as a major source of food, as well as their cultural foundation, could be damaged by bioaccumulation from the contaminated estuary. This intersection of science and outreach convinced Matt he wanted to pursue a higher degree, but he decided to go abroad for a short time before putting his nose to the grindstone!

You’ll have to tune in to hear where Matt’s explorations led him, and how nano-technology is becoming an increasing popular method for chemical delivery across scientific disciplines and industries. You can listen on October 16th 2016 at 7PM on the radio at 88.7FM KBVR, or stream live.

Orange you glad you have scientists?

Although many students know the Linus Pauling building, few know of the ridicule he faced towards the end of his career for pursing the effects of high dose Vitamin C on the human body and its implications for cancer treatment. Fast-forward a few decades and the tune has changed in scientists around the world as we begin uncovering the mechanisms of how Vitamin C influences cancer cell propagation. One of these projects is led by our guest this week Matt Kaiser who began this research project as an undergraduate which has helped make sense of why these pharmacological dosing levels of Vitamin C aid in targeting tumor cells while simultaneously allow the functioning of normal cells to remain uninhibited.

OSU 2015 Commencement Address
Matt has already presented at a professional conference in Boston, was an invited speaker at OSU’s TEDx event in 2015, helped start a philanthropy to donate money to OHSU, and pursued a six-month internship with one of the largest medical institutions in the country.. and he’s not done yet!

Currently Matt is working under Nancy Kerkvliet in the department of Environmental and Molecular Toxicology on a new project that can have breakthrough immunotherapy applications to help treat individuals with autoimmune diseases such as diabetes or multiple sclerosis.

You can see some of Matt’s photography work that helped contribute to Phil Knight’s Cancer Challenge by finding him on Instagram @backyard_oregon or on his website.

2015 TEDxOregonStateU

 

Join us Sunday, January 10th at 7PM to hear more about Matt’s research and his astonishing undergraduate career that has launched him to fame on the TED stage. Tune in to KBVR Corvallis 88.7FM or stream the show live!