Monthly Archives: July 2018

How do bone cancer cells become resistant to chemotherapy?

Limited treatments for bone cancer Bone cancer is a devastating and poorly understood disease with few available treatment options in humans. The disease disproportionately impacts young adults and children, and treatment still often includes amputation of the affected limb. Relapse within one year is common. Dogs can also spontaneously develop bone cancer, which makes them a suitable model for comparative oncology: insights about disease progression in dogs can yield insights about the disease in humans.

Animal models – one size does not fit all The difficulty of establishing a robust animal model has impeded scientists’ ability to study bone cancer rigorously. For example, although mice are commonly used to study human disease, they do not develop bone cancer spontaneously. Invasive tumor tissue grafts are required to study the disease in mice, which adds confounding variables to the results – it is not necessarily clear if an observed effect is the result of the tumor or the grafting procedure.

Understanding how chemotherapy resistance develops As a 2nd year Master’s student in the College of Veterinary Medicine, Marcus Weinman is working towards understanding how bone cancer tumors adapt and acquire resistance to chemotherapy. He has been developing canine osteosarcoma cell lines to study disease progression, which entails exposing cells to chemotherapy until they become resistant. Using a variety of molecular biology techniques, Marcus investigates how cells acquire resistance, and whether specific molecules or groups of molecules are more active or less active as resistance develops. The goal is to identify possible targets within the cell that might be sensitive to therapeutic intervention.  

Complexity of bone cancer cells Cells contain exosomes – small packages containing a diverse mix of molecules – that participate in signaling and transfer of molecules between cells. These compact cellular packages are being investigated for their role in the development of resistance. These tumor cells are also endocrine tumors – they express hormones normally found in other tissues, such as the brain and the gut – which adds a layer of physiology to the already-complex nature of cancer.

Why cancer research? Originally from Denver, Colorado, Marcus knew he wanted to attend OSU to pursue research opportunities. He completed his undergraduate studies at OSU, and attributes part of his desire to attend OSU to a deep family connection to Corvallis – his grandfather was a professor at OSU!

After completing his Master’s, Marcus plans to attend med school, with the eventual goal of becoming an oncologist, while maintaining his connection to research. He emphasizes how the teaching component of medicine is a motivating factor in his desire to become a physician. As a clinician, he would like to teach patients how to take care of themselves by integrating educational and interpersonal aspects of medicine.

Join us on Sunday, July 29th at 7pm on KBVR Corvallis 88.7 FM or stream live to hear more from Marcus about his research and experience as a graduate student at OSU.

 

Don’t just dream big, dream bigger

If you’ve purchased a device with a display (e.g. television, computer, mobile phone, handheld game console) in the last couple decades you may be familiar with at least some of the following acronyms: LCD, LED, OLED, Quantum LED – no, I did not make that up. Personally, I find it all a bit overwhelming and difficult to keep up with, as the evolution of displays is so rapidly changing. But until the display replicates an image that is indistinguishable from what we see in nature, there will always be a desire to make the picture more lifelike. The limiting factor of making displays appear realistic is the number of colors used to make the image. Currently, not all color wavelengths are used.

Akash conducting research on nanoparticles.

This week’s guest, Akash Kannegulla studies how light interacts with nanostructure metals for applications to advance display technology, as well as biosensing. Akash is a PhD candidate in the Electrical Engineering and Computer Science program with a focus in Materials and Devices in the Cheng Lab. Exploiting the physical and chemical properties of nanoparticles, Akash is able to work toward the advancement of display and biosensing technologies.

When shining light on metals, electrons and photons interact and oscillate to create a surface plasma, or “electron cloud”. Under specific conditions, when fluorescent dye is excited with UV light on the surface plasma, electrons move to higher atomic levels. When the electrons return to lower atomic levels, energy is released in the form of light. This light is 10-100X brighter than it would be without the use of fluorescent dyes. With this light magnification, less voltage is used to produce a comparable brightness level. This has two main benefits; first consumer products can use less energy to produce the same visual experience, so we can significantly decrease our carbon footprint. Second, these unique conditions can be amplified at the nano-scale, which means smaller pixels and more colors that can be produced so our TV screens will look more and more like the real world around us. These new advancements at the nano-scale have extremely tight tolerances in order for it to work; however, in this case, not working can also provide some incredible information.

This technology can be applied in biosensing to detect mismatches in DNA sequences. A ‘mismatch’ in a DNA sequence has a slightly different chemical bond, the distance between the atoms is ever so slightly different than what is expected, but that tiny difference can be detected by how intense the light is – again the nanoscale is frustratingly finnicky at how precise the conditions must be in order to get the expected response – in this case light intensity. So when we get a ‘dim’ spot, it can be indicative of a mismatched DNA segment! Akash predicts that in a just a few years, this nanotechnology will make single nucleic acid differentiations detectable on with sensing technology on a small chip or using a phone camera, rather than a machine half the size of MINI Cooper.

Akash, the entrepreneur, with his winning certificate for the WIN Shark Tank 2018 competition.

In addition to Akash’s research, he has spent a significant portion of his graduate career investing in an award-winning start-up company, Wisedoc.This project was inspired by the frustration Akash felt, and probably all graduate students and researchers, when trying to publish his own work and found himself spending too much time formatting and re-formatting rather than conducting research. By using Wisedoc, you can input your article content into the program and select a journal of interest. The program will then format your content to the journal’s specifications, which are approved by the respective journal’s editors to make publishing academic articles seamless. If you want to submit to another journal, it only takes a click to update the formatting. Follow this link for a short video on how Wisedoc works. And for those of us with dissertations to format, no worries – Wisedoc will have an option for that, too. Akash notes that Wisedoc would not have been possible without the help of OSU’s Advantage Accelerator program, which guides students, faculty, staff, as well as the broader community through the start-up process. Akash’s team has won the Willamette Innovators Network 2018 Shark Tank competition, which earned them an entry into the Willamette Angel Conference, where Wisedoc won the Speed Pitch competition. If you are as eager as I am to checkout Wisedoc, the launch is only a few months away in December 2018!

The soon-to-be Dr. Akash Kannegulla – his defense is only a month away – is the first person in decades from his small town at the outskirts of Hyberabad, India, to attend graduate school. Akash’s start in engineering was inspired by his uncle, an achieved instrumentation scientist. Not knowing where to start, Akash adopted his uncle’s career choice as an engineer, but took the time to thoroughly explore his specialty options while an undergraduate. A robotics workshop at his undergraduate institution, Amirta School of Engineering in Bangalore, India, sparked an interest in Akash due to the hands-on nature of the science. Akash explored undergraduate research opportunities in the United States landing on a Nano Undergraduate Research Fellowship from University of Notre Dame. During the summer of 2013, Akash studied photo induced re-configurable THz circuits and devices under the guidance of Dr. Larry Cheng and Dr. Lei Liu. Remarkably, Akash conducted research resulting in a publication after only participating in this four-week fellowship. After graduating with the Bachelor of Technology in Instrumentation, Akash decided to come to Oregon State University to continue working with Dr. Cheng as a PhD student.

After defending, Akash will be working at Intel Hillsboro, as well as preparing for the launch of Wisedoc in December. And if that doesn’t sound like enough to keep him busy, Akash has plans for two more start-ups in the works.

Join us on Sunday, July 22 at 7 PM on KBVR Corvallis 88.7 FM or stream live to learn more about Akash’s nanotechnology research, start-up company, and to get inspired by this go-getter.

 

The Mold That Keeps On Giving

All around us, plants, fungi, and bacteria are waging chemical warfare against one another to deter grazing, prevent against infection, or reduce the viability of competitor species. Us humans benefit from this. We use many of these compounds, called secondary metabolites, as antibiotics, medicines, painkillers, toxins, pigments, food additives, and more. We are nowhere close to finding all of these potentially useful compounds, particularly in marine environments where organisms can make very different types of chemicals. Could something as ordinary as a fungus from the sea provide us with the next big cancer breakthrough?

Paige Mandelare with one of the many marine bacteria she works with

Paige Mandelare thinks so. As a fourth-year PhD student working for Dr. Sandra Loesgen in OSU’s Chemistry department, she has extracted and characterized a class of secondary metabolites from a marine fungus, Aspergillus alliaceus, isolated from the tissues of an algae in the Mediterranean Sea. After growing the fungus in the laboratory and preparing an extract from it, she tested the extract on colon cancer and melanoma cell lines. It turned out to be cytotoxic to these cancer cells. Further purification of this mixture revealed three very similar forms of these new compounds they called allianthrones. Once Paige and her research group narrowed down their structures, they published their findings in the Journal of Natural Products.

Next, she grew the fungus on a different salt media, replacing bromine for chlorine. This forced the fungus to produce brominated allianthrones, which have a slightly different activity than the original chlorinated ones. Her lab then sent two of these compounds to the National Cancer Institute, where they were tested on 60 cell lines and found to work most effectively on breast cancers.

The recent publication of Paige in her story of the allianthrones from this marine-derived fungus, Aspergillus alliaceus.Like many organisms that produce them, this wonder mold only makes secondary metabolites when it has to. By stressing it with several different types of media in the lab, Paige is using a technique called metabolomics to see what other useful compounds it could produce. This will also give insight into how the fungus can be engineered to produce particular compounds of interest.

A native Rhode Islander who moved to Florida at the age of ten, Paige has always been fascinated with the ocean and as a child dreamed of becoming a marine biologist and working with marine mammals. She studied biology with a pre-med track as an undergraduate at the University of North Florida before becoming fascinated with chemistry. Not only did this allow her to better appreciate her father’s chemistry PhD better, she joined a natural products research lab where she first learned to conduct fungal chemical assays. Instead of placing her on a pre-med career path, her mentors in the UNF Chemistry department fostered her interest in natural products and quickly put her in touch with Dr. Loesgen here at OSU.

Paige enjoying her time at the Oregon Coast, when she is not in the research lab

After finishing her PhD, Paige hopes to move back east to pursue a career in industry at a pharmaceutical company or startup. In the meantime, when she’s not discovering anticancer agents from marine fungi, she participates in a master swimming class for OSU faculty, trains for triathlons, and is an avid baker.

To hear more about Paige and her research, tune in to KBVR Corvallis 88.7 FM this Sunday July 15th at 7 pm. You can also stream the live interview at kbvr.com/listen, or find it on our podcast next week on Apple Podcasts.