Nishimura, Santangelo named 2017 Boettcher Investigators

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Anne Manning

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FORT COLLINS – Two Colorado State University biomedical researchers, Erin Osborne Nishimura and Kelly Santangelo, have received Webb-Waring Biomedical Research Awards from the Boettcher Foundation.

Nishimura and Santangelo join seven other top Colorado researchers in this year’s class of Boettcher Investigators, as they are called.

Now in its eighth year, the Webb-Waring Biomedical Research Awards program honors early-career researchers with three-year, $235,000 grants to advance their independent research and position them to compete for major federal and private awards. Previously honored CSU Boettcher Investigators are: Melissa Reynolds, John D. (Nick) Fisk, Tingting Yao, J. Lucas Argueso, Brad Borlee, Christopher L. Gentile, Tai Montgomery, Rushika Perera and Tim Stasevich.

To date, the Webb-Waring awards have supported 54 Boettcher Investigators at the state’s leading academic and research institutions.

“This year’s award recipients are doing important work that has the potential to significantly improve human health,” said Katie Kramer, CEO of the Boettcher Foundation. “The Boettcher Foundation is proud to help propel this research forward, because Colorado can only be a leader in scientific innovation if its most dynamic scientific minds are supported at early stages in their work.”

How cells’ identity crises lead to cancer

Nishimura is an assistant professor in the Department of Biochemistry and Molecular Biology. Her goal is to make fundamental breakthroughs in our understanding of cancer. Specifically, how does gene expression produce mature cells that “know” their proper cell identities ­– and why do cells sometimes “forget” who they are, and become cancerous?

Nishimura’s lab conducts high-resolution, genome-wide experiments to probe how cell identity arises in early embryonic stages. To date, they have employed a classical model system, the C. elegans nematode embryo. Nishimura’s group has comprehensively mapped all mRNA transcripts with single-cell resolution in the early embryo of this nematode worm.

Her Boettcher-supported project will use insights and tools honed in C. elegans and apply them to a human cell culture system that models cancer onset. The project will first combine her mRNA “atlas” with transcription factor and chromatin information to identify mechanisms that drive cell identity establishment. Then, the researchers will begin to address how cell identity is lost in a human cancer model.

“The Boettcher Foundation’s support will allow our lab to bridge our basic biology pursuits into translational avenues with more direct impact on human health,” Nishimura said.

Nishimura joined the CSU College of Natural Sciences faculty in January 2016, after completing postdoctoral work in Genomics and Developmental Biology at the University of North Carolina, Chapel Hill, and a Ph.D. in Plant Biology at the University of California, Berkeley.

Though she is new to Colorado, her father’s family has lived in Fort Collins and Greeley for generations, Nishimura says, having emigrated from present-day Russia, Kazakhstan, the Netherlands and Wales to Northern Colorado to become sugar beet farmers. The Boettcher family was instrumental in the founding of the Great Western Sugar Company, which pioneered the industry, Nishimura recently learned.

“I am excited to have been recruited to the state of Colorado, and I am eager to be a part of the innovative research environment here,” she says.

Tackling post-traumatic osteoarthritis

Santangelo, the first veterinarian to ever receive the Webb-Waring award, will explore “Prevention and therapy of post-traumatic osteoarthritis.”

Her research will investigate how, after traumatic injury, the interaction between Toll-like receptors — proteins that play a key role in the immune system — and damage-associated molecular patterns contribute to the development and progression of post-traumatic osteoarthritis.

Santangelo first became interested in osteoarthritis while in veterinary school at Cornell University. At the time, she had her sights set on becoming an equine orthopedic surgeon. After receiving a Doctorate of Veterinary Medicine at Cornell, she completed a residency in Clinical Pathology and earned a Ph.D. in Comparative and Veterinary Medicine at The Ohio State University. Along the way, Santangelo had decided to pursue a career in research.

Post-traumatic osteoarthritis is a debilitating condition that affects more than 27 million Americans. It results in a $3 billion annual burden in direct health-care costs, disability-affected life years and lost work productivity. The knee is most frequently affected, with over 900,000 cases of acute injury reported each year in the United States. There is no cure for post-traumatic osteoarthritis, and most patients require total joint replacement surgery when they reach end-stage disease.

Santangelo, an assistant professor in the Department of Microbiology, Immunology and Pathology, said that while having osteoarthritis might not be a direct cause of death, it limits a person’s mobility and can cause depression. Ultimately, it can have a very negative effect on a person’s health and well-being.

“Chronic pain is something, until you experience it, you don’t realize how debilitating it can be,” she said. “It can severely limit the ability for a person to go about normal daily functions.”

Santangelo said her goal is for people to maintain functional, pain-free mobility throughout aging for as long as possible.

Her research will explore injury-induced osteoarthritis, which affects military personnel and civilians. She plans to examine medications that are already approved by the U.S. Food and Drug Administration, though not necessarily for osteoarthritis. She will also explore human synovial fluid, which is found in people’s joints, to characterize what is in the fluid that is inviting inflammation.

“It would be great if we could prevent this type of osteoarthritis from occurring,” she said. “If we could lessen the pain, it would add a tremendous amount to a person’s quality of life. It never ceases to amaze me how much we take our mobility for granted, until something happens with it.”

Santangelo will collaborate on the project with researchers at the University of Colorado Denver and Rush University Medical Center in Chicago. She said this award means a “tremendous amount” to her.

“Our team has the potential to make an impact, and I am thankful for the Boettcher Foundation and CSU for supporting this work,” she said.