The 2016 Boettcher Investigators. Back row: Cristin Welle, Schuyler B. Van Engelenburg, Hongjin Zheng, Rushika Perera, Ethan G. Hughes, Timothy J. Stasevich, Bernard L. Jones, James L. Crooks. Front row: Wen-Yuan Elena Hsieh, Tim Schultz (exec. dir. Boettcher Foundation), Sabrina L. Spencer
Written by Kristen Browning-Blas and Anne Ju Manning
Two CSU researchers who study tiny organisms and their roles in two of humanity’s biggest health concerns – viruses and cancer – have received awards that will fund three years of research for their laboratories.
Rushika Perera, assistant professor of virology in the College of Veterinary Medicine and Biomedical Sciences, and Tim Stasevich, assistant professor of biochemistry and molecular biology in the College of Natural Sciences, each received $225,000 Webb-Waring Biomedical Research Awards through the Denver-based Boettcher Foundation. The foundation announced the awards Tuesday.
The scientists join the 2016 class of Boettcher Investigators, 10 early career researchers who are getting established in their fields. The foundation will support their work as they become competitive for major awards from federal and private sources.
Rushika Perera: Preventing mosquito-borne viruses
Perera has been named a Boettcher Investigator for “Exploiting Vulnerabilities in Mosquito Metabolism for the Prevention of Human Arboviral Transmissions.”
For the past three years, Perera has run a lab on CSU’s Foothills Campus, studying how dengue, chikungunya, yellow fever, and Zika viruses behave in their mosquito hosts. The World Health Organization estimates more than 3 billion people in over 100 countries are at risk of being exposed to these mosquito-borne diseases.
As mosquitoes become resistant to insecticides, researchers are looking for new ways to block disease transmission. Perera studies cutting-edge metabolomics approaches to identify metabolic “choke-points” that can be exploited to eventually block mosquito-human viral transmission.
Perera’s lab examines the mosquito digestive system, specifically the midgut. “My research focuses on what kind of biochemical changes are happening in the midgut that allow the virus to replicate, and can I control or block those changes to prevent virus replication?”
Once scientists understand the molecular activity in mosquitoes, they can try to interfere with those pathways, leading to new ways to reduce dengue, Zika and chikungunya transmission.
“I’m a virologist first, so I understand the virus, and now I am trying to understand the host,” Perera explained. “I’m using state-of-the-art technology, including mass spectrometry, to look at these metabolic changes.”
Her lab must raise and infect thousands of mosquitoes to study how the various viruses interact with their metabolism. They then dissect the tiny organs and use mass spectrometry to measure and identify the molecules within. She expects her findings to inform methods to prevent the spread of malaria, West Nile virus and other important pathogens that are transmitted by mosquitoes and other insects.
“You have to dissect a bunch of midguts because they are very tiny tissues. Then you send it for mass-spectrometry, and that’s the expensive part. Then you spend months evaluating the results. It’s a lot of work, but what comes out of it is really exciting information. It’s a tremendous technical feat,” Perera said.
“You have to look for new avenues for controlling these diseases. These new avenues are new because they’re difficult. I think it will be a completely uphill battle, but the good thing about the Boettcher is that it lets you take a risk – and that’s a huge gift to me.”
Tim Stasevich: Understanding the genetic underpinnings of cancer
Stasevich has been named a Boettcher Investigator for his project titled “Imaging cancer epigenetics with live cells.” Stasevich’s lab develops boundary-pushing fluorescence microscopy techniques to image proteins in living cells. Their goal is to better understand genetic processes and subsequently control and correct gene misregulation.
Supported by the Boettcher/Webb-Waring grant, Stasevich’s team will study how epigenetics in particular contribute to cancer development.
The genetic underpinnings of cancer form a significant biomedical question, and genetic mutations are central to the disease. It’s increasingly clear that epigenetics also play key roles in disease progression. Epigenetic modifications are heritable changes in gene expression that create new traits within the same genome. In other words, the genome is the cast of actors in the play; the epigenome is the lines, scenes, direction and staging. To cure disease, mapping the genome isn’t enough. It’s what all the individual genes do that make the difference in whether certain diseases manifest.
Stasevich’s group wants to image the epigenome in action, in vivo, and to test how it interacts with cancer-related genes. They will look at whether these interactions influence tumor malignance, using advanced microscopy to image epigenetic modifications to chromosomes in live cells. These modifications cannot be imaged with typical methods involving green fluorescent protein.
To accomplish this feat, the Stasevich lab will build on previous work using fluorescent antibody fragments. These antibody pieces, unlike green fluorescent protein, can distinguish between modified and unmodified proteins.
“This is interesting because modified chromatin proteins are implicated in cancers and are thought to interact with oncogenes and tumor suppressors, switching them on or off,” Stasevich said. “However, it is still not known what causes what. Do the modifications lead to cancer or are they merely symptoms of cancer? To answer this question, we need to image the modifications in living cells, something our lab is uniquely positioned to do.”
Investing in the state’s top minds
“We are proud to continue the Webb-Waring legacy by supporting Colorado’s top scientific minds. The research they are conducting has the potential to significantly improve human health, and we are honored to help these talented scientists bring their research to the next level,” said Tim Schultz, president and executive director of the Boettcher Foundation.
The awards were announced jointly by Boettcher and the Colorado BioScience Association. Now in its seventh year, the Webb-Waring Biomedical Research program honors the commitments of the Webb and Waring families to scientific research and public service. Including the Class of 2016, 45 Boettcher Investigators at the state’s leading academic and research institutions have received funding through the Webb-Waring program.
“Colorado’s life science sector values our most promising scientific minds, which contribute to building a robust ecosystem in our state,” said April Giles, president and CEO of the bioscience association. “The Boettcher Foundation and the Webb-Waring Biomedical Research Awards make a long-term commitment in support of that goal. We are grateful to the foundation for advancing scientific research in Colorado through its early investments in people and their possibilities.”