Author Archives: Heather Forsythe

Kayaks and Computers: the Gray Whale Research Essentials

Throughout the year, looking out from the Oregon coast, you can often spot gray whales with the naked eye. Behind the magic and mystery of these massive creatures are teams of researchers tracking their migration and studying their diet.

Lisa Hildebrand is a 1st year Master’s student in Wildlife Science working with Dr. Leigh Torres within the College of Agriculture. Lisa studies geospatial ecology of marine megafauna, meaning that her research focuses on the feeding and movement through time and space of sea creatures larger than most fish, including large sea birds, seals, dolphins, and of course, the gray whales. To study such large animals in the ocean, Lisa manages a team that combines diverse technologies coupled with fine scale foraging ecology.

Gray whales feed on very small zooplankton suspended in shallow water. The whales don’t have teeth but instead have rows of baleen which look like a thick brush and act as a filter for water and sediment while letting in large quantities of zooplankton. In July and August, Lisa and her team of 4-5 people go out to Port Orford, Oregon. The team splits into two groups: a cliff team and a kayak team. From a cliff above their 1km2 sampling site, theodolites and computational programs are used to track whales by height and GPS location. Once a whale is spotted, team members kayak to this location and take water samples for analysis of zooplankton density, caloric content, species, and microplastic quantity. Lisa has taken over this ongoing project from a previous Master’s student, Florence Sullivan, and has data on the same research site and whales going back to 2015.

This research project provides opportunities for both undergraduates and high school level students to obtain first-hand field research experience. The students involved are able to take what they’ve heard in a classroom and apply it outdoors. In particular, Lisa is passionate about getting the students in the local Oregon coastal community involved in research on the whales that bring many tourists to their area.

To study the large gray whales, Lisa spends most of her time studying the small zooplankton that they eat. Zooplankton hide under kelp and it turns out, can be separated by populations that are pregnant, or varied in age or species. Gray whales may show preference for some feeding sites and/or types of zooplankton. Why do we care what a gray whale’s dietary preferences are? Plastic use and plastic pollution are rampant. Much of our plastic ends up in the oceans and photodegrade into microplastics small enough to be consumed by zooplankton. Since gray whales are the top predator for zooplankton and eat large qualities, these microplastics accumulate. Microplastic presence may differ between regions and species of zooplankton, which may relate back to whale preferences and migratory patterns. On the Oregon coastline, microplastic profiles of zooplankton have not yet been studied. As humans are also consuming large quantities of seafood, it is important to understand how microplastics are accumulating in these areas.

Lisa is from Germany and grew up in Vietnam and Singapore, but she was first inspired to pursue marine animal research as a career after a family trip to Svalbard, Norway during high school. Before obtaining her undergraduate degree in Marine Zoology from Newcastle University in England, Lisa took two years off from schooling and completed two internships: one with bottlenose dolphin sanctuary research institute in Italy and Spain, and one at a seal research facility in Germany. Now that she’s settled in Oregon for now, Lisa is enjoying the nature and in her free time loves hiking and skiing.

To learn more you can check out GEMM Lab website , the GEMM Lab blog and Lisa’s Twitter, @lisahildy95

To hear more about Lisa’s research, tune in Sunday, January 20th 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!

Treating the Cancer Treatment: an Investigation into a Chemotherapy drug’s Toxic Product

One of the most difficult hurdles in cancer treatment development is designing a drug that can distinguish between a person’s healthy cells and cancer cells. Cancerous cells take advantage of the body’s already present machinery and biochemical processes, so when we target these processes to kill cancer cells, normal, healthy cells are also destroyed directly or through downstream effects of the drug. The trick to cancer treatment then is to design a drug that kills cancer cells faster than it harms healthy cells. To this end, efforts are being made to understand the finer details that differentiate the anti-cancer effects of a drug from its harmful effects on the individual. This is where the research of Dan Breysse comes in.

Dan a third-year master’s student working with Dr. Gary Merrill in the department of Biochemistry and Biophysics. Dan’s research focuses on a common chemotherapy drug, doxorubicin. Doxorubicin has been researched and prescribed for about 40 years and has been used as a template over the years for many other new drug derivatives. This ubiquitous drug can treat many types of cancer but the amount that can be administered is limited by its toxic effect on the individual. Nicknamed “the red death,” doxorubicin is digested and ultimately converted to doxorubicinol, which in high doses can cause severe and fatal heart problems. However, hope lies in the knowledge that doxorubicinol generation is not related to the drug’s ability to kill cancer cells. These mechanisms appear to be separate, meaning that there is potential to prevent the heart problems, while keeping the anti-cancer process active.

Cancer cells replicate and build more cellular machinery at a much faster rate than the majority of healthy cells. Doxorubicin is more toxic to fast-replicating cancer cells because its mechanism involves attacking the cells at the DNA level. Dividing cells need to copy DNA, so this aspect of doxorubicin harms dividing cells faster than non-dividing cells. It is common for chemotherapy drugs to target processes more detrimental to rapidly dividing cells which is why hair loss is often associated with cancer treatment.

Separately, doxorubicin’s heart toxicity appears to be regulated at the protein level rather than at the DNA level. Doxorubicin is converted into doxorubicinol by an unknown enzyme or group of enzymes. Enzymes are specialized proteins in the cell that help speed up reactions, and if this enzyme is blocked, the reaction won’t occur. For example, an enzyme called “lactase” is used to break down the sugar lactose, found in milk. Lactose intolerance originates from a deficiency in the lactase enzyme. During his time at OSU, Dan has been working to find the enzyme or enzymes turning doxorubicin into doxorubicinol and to understand this chemical reaction more clearly. Past research has identified several potential enzymes, one of which being Carbonyl reductase 1 (CBR1).

Doxorubicin is converted to doxorubicinol with the addition of a single hydrogen atom.

While at OSU, Dan has ruled out other potential enzymes but has shown that when CBR1 is removed, generation of doxorubicinol is decreased but not completely eliminated, suggesting that it is one of several enzymes involved. In the lab, Dan extracts CBR1 from mouse livers, and measures its ability to produce doxorubicinol by measuring the amount of energy source consumed to carry out the process. To extract and study CBR1, Dan uses a process called “immunoclearing,” which takes advantage of the mammal’s natural immune system. Rabbits are essentially vaccinated with the enzyme of interest, in this case, with CBR1. The rabbit’s immune system recognizes that something foreign has been injected and the system creates CBR1-specific antibodies which can recognize and bind to CBR1. These antibodies are collected from the rabbits and are then used by Dan and other researchers to bind to and purify CBR1 from several fragments of mouse livers.

Prior to his time at OSU, Dan obtained a B.S. in Physics with a concentration in Biophysics from James Madison University where he also played the French horn. Realizing he loved to learn about the biological sector of science but not wanting to completely abandon physics, Dan applied to master’s programs specific to biophysics. Ultimately, Dan hopes to go to medical school. During his time at OSU, he has balanced studying for the MCAT, teaching responsibilities, course loads, research, applying to medical schools, and still finds time to play music and occasionally sing a karaoke song or two.

To hear more about Dan’s research, tune in Sunday, December 16th 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!

Finding cancer with sound: the development of nanoparticles to deliver light-to-sound converting agents

“Here I am!” -Cancer

Wouldn’t it be nice if cancer could simply yell out to let us know where it is, and how much of it is there? Anna St. Lorenz, a 4th year PhD student in the College of Pharmacy, is working on just that.

Anna volunteering at Brain Day at OMSI science museum.

Anna’s path to scientific research began when she was 8 years old, on a farm, with some chickens and a candle-lit microscope. Anna spent much of her childhood becoming familiar with the local ecology, as well as the Mendelian laws of genetic inheritance that applied to her family’s chicken breeding. However, her first taste of research was in Death Valley. With funding provided through Smith College associated religious programs, Anna studied arsenic-eating-microbes, but thanks to some giant spiders and allergies, Anna decided field research wasn’t for her and moved to a hospital setting.

In college, Anna’s scientific education expanded further through multiple internships and unique educational opportunities at Novartis Pharmaceuticals, Dana-Farber Cancer Institute and OHSU. Anna obtained a B.A. in Biology with a minor in Neuroscience from Smith College. Receiving a B.A. rather than a B.S. meant that Anna’s science education was interdisciplinary, and incorporated disciplines such as history and the fine arts. Anna’s love of the arts still persists as she frequently paints and creates “bioart,” which she uses as a means to inform and involve the community on her scientific endeavors. She commonly uses her work with her husband, Grey St. Lorenz, in presentations and has previously collaborated with artists in upstate New York for work on display at local universities. 

Bioart by Anna. Nanoparticles taken up by an endosome, that then create a pore in the endosome’s membrane to release their payload. It is done in the style of Starry Night and the nanoparticle’s payload matches up with the stars.

After completing her undergraduate degree, Anna received a Master’s in Biomedical Engineering from Rensselaer Polytechnic Institute. While finishing up her Master’s degree, Anna moved to Boston and started working at MIT as a nanoparticle research technician within the Langer Lab. It was at MIT that she learned about a new nanoparticle-specific program being implemented in the OSU College of Pharmacy. This program is now about four years new and Anna has been at the front line of pioneering this program for future graduate students. In addition to navigating a new program and coping with the regular difficulties of being a graduate student, this OSU nanoparticle program is actually based at the Oregon Health & Science University (OHSU) in Portland. Although challenging at times, as a graduate student researching cancer therapeutic technology, OHSU is great place to be.

Anna and the Taratula group.

In this program, Anna works with the Taratula group on ovarian cancer diagnosis. As a disease that is traditionally hard to detect at early stages, it is often only after the cancer has spread to other areas of the body in later stages that diagnosis is able to be made. This metastasis results in a worse prognosis and decreased survival rates. To this end, Anna and other researchers and medical professionals are developing nanoparticles to deliver various iterations of imaging agents. Anna’s role in this process is to design more specific nanoparticles to carry various agents through the bloodstream and allow for specific staining of cancerous tissue.

Bioart by Anna and Grey St. Lorenz demonstrating a nanoparticle (blue) encapsulating a compound (red) and adorned with targeting antibodies (green).

Have you ever used facewash with textured particles in it?  Nanoparticles are 1/1000th of that size and are used to envelop or otherwise transport compounds throughout the body and deliver them to more specified regions. This technology can be applied to a variety of compounds to enhance their delivery needs. Solubility issues, tissue or disease specificity, PH, heat, and enzyme specific release are all areas that nanoparticle science delves into to address patient care. So now, the imaging agent, inside of its tiny carrier, can circulate through the body and find the cancerous tissue it’s designed to target.

As tumors are characteristically disorganized tissue whose unregulated growth demands increased nutrients, they develop a leaky vasculature  which makes it easier for molecules to permeate the tissue. Once the nanoparticle reaches the tumor, it is able to take advantage of the enhanced permeability of tumors to infiltrate and label the cancer cells. An important characteristic of the works is that the compounds use near-infrared (near-IR) light, which can be administered to excite the delivered agents in a spectral range that is largely unaffected by organic tissue. These agents were specifically screened for their ability to convert this light to acoustic/sounds waves that are detectable by ultrasound imaging.  This process allows for an enhanced detection and characterization of ovarian cancer – opening the door for effective screening and improved monitoring of this devastating disease.

Join us Sunday November 4th at 7PM on 88.7FM, or listen live, to learn more about Anna’s exciting journey to graduate school, bioart, sound-making cancer, and nanoparticles.