Kidney-On-A-Chip In Space: With support from the EDGE Center, a UW team prepares to send their revolutionary simulation kidney into space

Most drugs a person takes will ultimately be cleared from their body into urine by their kidneys. The role of these hard-working organs in drug clearance makes them particularly susceptible to the toxic effects of certain medications. Unfortunately, unlike livers, kidneys can’t regenerate. That’s bad in part because, once they start to fail, they limit the ability of a patient to process drugs—complicating treatment for a range of diseases, including kidney disease.  
In the past, a medical researcher who wanted to test the effects of a new drug on the kidneys might have applied the drug to cultured kidney cells on a plate. Regrettably, that test wouldn’t model what happens in the body very well because it wouldn’t replicate blood flow. A more expensive and ethically complicated option would be to conduct tests on animals.  However, animals are not always predictive of human responses.

Fortunately, a recent breakthrough by a team co-led by EDGE members, Edward Kelly, and Jonathan Himmelfarb, with colleague Catherine Yeung, gives researchers a new option—kidney-on-a-chip. While it might sound like some kind of British hors-d'oeuvres, kidney-on-a-chip is actually a revolutionary new device that functions as a normal kidney, allowing researchers to test drugs as well as xenobiotics in a much more natural laboratory model.
The genius of kidney-on-a-chip is that it incorporates flow to mimic normal kidney function. A tubule of kidney cells are enclosed inside a plastic case through which drugs can be passed in a system that closely replicates a working kidney. Researchers can apply experimental drugs to kidney-on-a-chip with a syringe, pushing medications through the system—even multiple medications at once—without the need for gravity.  
Kelly and Himmelfarb are already using kidney-on-a-chip to compare the toxicity of antibiotics and herbal products on the kidney to compare the effects of different doses. By detecting harmful effects with the chip, they’re able to optimize treatment options for patients while reducing the need for human and animal testing. In the future, they hope to use the chips not only to improve treatment and prevention of disease but also to develop cures.

As exciting as the chip advance has been for kidney research, it’s about to get better. Thanks to recent federal grants from the National Institutes of Health’s National Center for Advancing Translational Science and NASA’s Center for the Advancement of Science in Space, kidney-on-a-chip is preparing for its first cosmic voyage—to the International Space Station.
Why send kidney-on-a-chip to space? Because there’s so much to learn. First of all, microgravity will speed up processes related to the development of kidney disease, so that problems that take decades to develop on Earth could appear within weeks or months in space. This will potentially give researchers rare insights into the long-term effects of drug treatment.
Second, studying kidney-on-a-chip in space can provide important insights into the medical complications associated with weightlessness. Bone loss is one problem that plagues astronauts. Kidneys make the active form of vitamin D that keeps bones healthy, so it’s important to understand how that function occurs in a weightless environment.
Cells have never been sent to space like this. This experiment will allow scientists to probe the long-term effects of a lower-gravity environment on a human organ. What the team learns will dramatically improve our understanding of issues like potential medical challenges for Mar’s first colonists. As Yeung explains it, “This is experimental in the truest sense of the word, which is incredibly exciting.”

Kidney-on-a-chip project co-lead, Edward Kelly, is an Associate Professor in the University of Washington (UW)’s School of Pharmacy and directs the EDGE microphysiological systems unit. Co-lead, Jonathan Himmelfarb, holds an Endowed Chair in Kidney Research at the UW School of Medicine, directs the Kidney Research Institute, and co-leads the EDGE Collaborative Research Team (CRT) on Hepatic, Renal and GI Diseases. Terrance Kavanagh, EDGE Science Director, and Elaine Faustman, co-lead of the EDGE Developmental and Reproductive Disorders CRT, co-direct a predictive toxicology group that supported the development of kidney-on-a-chip and continues to support the use of this technology for environmental health research.

UW EDGE’s Catherine Karr featured in The Lancet for her work to address disparities in environmental health

Catherine Karr, Director of EDGE’s Clinical and Translational Sciences Unit, helps a participant in the Home Air in Agriculture; Pediatric Intervention Study (HAPI) use a device to measure airway inflammation at the Yakima Valley Farm Workers Clinic in Toppenish, WA. Photo credit: Lisa Younglove.
A recent profile in The Lancet describes Dr. Catherine Karr, Director of EDGE’s Clinical and Translational Sciences Unit, as “the best of a new breed of physician-scientists that are patient-centered, community-centered, and justice-centered.” The quote comes from Ruth Etzel, Director of the US Environmental Protection Agency’s Office of Children’s Health Protection.

Karr’s research focuses on the ways in which a child’s environment affects their long-term health and development and the disparities that characterize those impacts. Specifically, she has investigated the role of environmental contaminants in the health of children with asthma in Latino farmworker children living in Washington State’s Yakima Valley. Her work brought attention to the role of crop production, emissions from industrial-scale dairy production, and smoke from winter wood stove use in worsening asthma. Currently, she’s studying whether a combination of asthma education and the use of indoor portable air cleaners can improve children’s health.

Karr also leads NEXTGENNS, a project to address wood smoke with the Yakama Nation community and she is involved in the National Institute of Health’s Environmental Influences on Child Health Outcomes (ECHO) consortium. The goal of ECHO is to understand the effects of early life environmental influences, including chemicals and stress, on subsequent child health and development. One of these influences is exposure to lead, a topic of which Karr is an expert, and about which she was recently interviewed by KIRO 7 as part of a story about high levels of lead found in Washington schools.

Another theme that runs throughout Karr’s work is her emphasis on outreach. As she points out in The Lancet profile, “We are still not very good at communicating the pay-off of healthy environments on population health to key decision makers in government. Doctors also need to know more about the role of environment in their patient's health. It is both part of prevention and sometimes cure.”

Karr holds a masters degree in toxicology, a medical degree, and a Ph.D. in epidemiology. She is currently a Professor of Pediatrics and Environmental and Occupational Health Sciences at the University of Washington as well as Director of the NW Pediatric Environmental Health Specialty Unit. Read the full profile of Karr in The Lancet here.

UW EDGE Center co-organizes a trans-disciplinary workshop to discuss the future of local fisheries

By Victoria Pinheiro, Nereus Program Strategic Communications Lead, original story published here.

Nereus Program Policy Director Yoshi Ota, and Swinomish tribal elder Larry Campbell converse during a Fish and Future breakout session. Photo Credit: Colby K. Neal.
On April 3rd, 2018, tribal representatives, students, and academics gathered to discuss a pressing issue for coastal indigenous communities of the Pacific Northwest: the future of the fish they’ve relied on since time immemorial. Climate change, pollution, and toxic algae blooms are threatening the survival of salmon and shellfisheries relied upon by both the Native American tribes in Washington State and First Nations in British Columbia. These fisheries represent significant nutritional and economic value to both peoples, and they also have deep running cultural importance. All three aspects were considered during the gathering entitled Fish and Future held at the University of Washington’s wǝɫǝbʔaltxʷ (“Intellectual House” in the Luhshootseed language). The building was inspired by the traditional Long Houses of the Coastal Salish people, with lofty cedar walls and beams overlaid with indigenous artwork. Traditional song and drumming filled the space as Willard Bill Jr, Cultural Director of the Muckleshoot Tribe and his son, Justice Bill, delivered a welcome prayer to commence the meeting. The words, music, and setting created an unrivaled sense of place and purpose. “We are here,” Bill told us, referring to the Indigenous People of the Pacific Northwest. “We are alive and strong. We are from here – we’ve never been from anywhere else.”

Justice Bill and his father, Cultural Director of the Muckleshoot Tribe Willard Bill Jr., lead welcome prayer to commence the meeting. Photo Credit: Colby K. Neal
The environmental threats to the fisheries relied upon by 37 million coastal indigenous populations are born from the actions of developed nations, making food sovereignty for these groups a pressing issue of global equity. “Forty-one percent of First Nations people in BC experience food insecurity,” explained Dr. Laurie Chan. “Ninety-one percent of people surveyed want to eat more traditional food but simply don’t have access to it any longer. This is an issue for a number of reasons; one being because diets are healthier when more traditional food is eaten than market food.” And conditions are likely to get worse, Chan explained. “Under the influence of climate change, projections show a considerable decline of fish stocks along the coast of British Colombia. This could result in a decrease of healthy food and essential nutrient intake and also has a negative impact on the well being of the people’s culture.” In other words, this isn’t just a loss of nutrients; it’s a loss of heritage.

Dr. Sara Jo Breslow of the University of Washington's Center for Creative Conservation led workshop participants in an interactive reading from her play The Last Best Place which was created using transcripts from interviews with local farmers, scientists, and tribal members. Photo Credit: Colby K. Neal
The format of the gathering was innovated to inspire and generate creative thinking about what needs to be done. Academic talks and presentations were interspersed with a film screening of Colby K. Neal’s Broken Fish and an interactive reading from The Last Best Place, a play about salmon, people, and habitat by Dr. Sara Jo Breslow. Breslow’s play arranges the words of tribal members, farmers and scientists taken down during anthropological interviews to tell the story of the human-salmon ecosystem in the Pacific Northwest. She gathered eleven members of the audience around a table and handed them each a script. “But there are days when I wonder, if all what they really want, is control over what you do? Or do they really want to save fish?… And you know, you might not understand this, but my family’s been here for 110 years. That’s a long time. This land is my heritage and I intend to pass it on to my grandchildren,” read one participant, speaking the words of a farmer frustrated by restoration regulations. “It staggers me that someone could say that to, say, members of an Indian tribe,” replied another participant, speaking the words of a tribal staff person. “That, you know, to – to whom one hundred and ten years is not even a blink of an eye.” Participants were able to experience the perspective of the character they played, regardless of how different it was from their own, and speak the words of another human with feeling and empathy.

The morning’s proceedings inspired a generative planning session in the afternoon. Participants proposed creating a task force to align ongoing efforts, and to integrate Indigenous and western-based sciences to develop strategic adaptation and action plans. “When we take inquiry back to the tribal community, we get history, community, and culture along with the research objective,” said Swinomish tribal elder Larry Campbell. The meeting ended on a note of progress and excitement about new plans and initiatives inspired by the day’s dialogue. “All of the organizations here presumably started with a first meeting,” said Dr. Elaine Faustman. “I know this meeting will be the start of something new for many of you.”