Introducing Dr. Libin Xu

Dr. Libin Xu joined the Center for Ecogenetics and Environmental Health this year as an Affiliate Member. Dr. Xu is a researcher and Assistant Professor in the Department of Medicinal Chemistry in the UW School of Pharmacy. 

Libin studies lipids, or fat molecules (cholesterol, vitamin A and vitamin E are examples), and their oxidation, a chemical reaction that generates free radicals that can damage DNA and body tissues. Having too many free radicals leads to oxidative stress, but this process can be prevented by antioxidants made in our own body or absorbed from diet. The Xu Lab studies how certain lipids are oxidized and metabolized, and how oxidation during lipid metabolism might be involved in human diseases.

The Xu lab is studying a rare disease called Smith-Lemli-Opitz syndrome or SLOS. SLOS is a cholesterol disorder that causes problems in the development of the central nervous system starting at embryonic stages. People who have SLOS have birth defects, intellectual disability and behavior problems such as autism.

SLOS is caused by a mutation in a gene (DHCR7) that makes an enzyme (3β-hydroxysterole-Δ7-reductase) that turns one lipid molecule (7-DHC) into another (cholesterol). The mutation means that SLOS patients have a lot of 7-DHC and not enough cholesterol. And it turns out that 7-DHC is extremely reactive toward oxidation, leading to the formation of free radicals and toxic oxidation products called oxysterols. In addition, some oxidative enzymes (cytochrome P450) can also turn 7-DHC into toxic oxysterols. This may be the problem underlying SLOS.

The goal of the work in Dr. Xu’s lab is to figure out the exact biochemical processes that lead to the broad phenotype of SLOS, and to find therapies to improve SLOS and other diseases caused by disrupted lipids. This research also will help scientists understand other intellectual and developmental disabilities that are associated with lipid metabolism problems and affect the function of the brain.

The research tools being developed in Dr. Xu’s lab to study lipids, based on advanced mass spectrometry, can also be used to study the side effects that common drugs might have on the metabolism of lipid molecules.

Working with the CEEH Community Outreach and Engagement Core (COEC), Libin Xu and Andrew Dinh in the Xu Lab have created a handout of interest to the general public: Fast Facts about Fat-Soluble Vitamins. Libin has also agreed to talk about lipid oxidation and his research at a Public Health Café next year.
Dr. Xu graduated with a B.Sc. in Chemistry from Nankai University, Tianjin, China. He earned his PhD in Organic Chemistry from the University of Illinois at Chicago, and did a post-doc at Vanderbilt where he became interested in lipid peroxidation and its role in human diseases.  He received the Young Investigator Award from the Society for Free Radical Biology and Medicine in 2011 and the NIH Pathway to Independence Award from the National Institute of Child Health and Human Development in 2012. We welcome Libin Xu to the CEEH.                                                         
                                                                                                                                    --Marilyn Hair

Celebrating the new Port Gamble S'Klallam Environmental Health Children's Book, taʔt̕ə́wəsnaʔ

Author and Port Gamble S'Klallam tribal member Tleena Ives organized a Book Release for her children's book, taʔt̕ə́wəsnaʔ Star. 

Tleena's book was the result of her collaboration with the Center for Ecogenetics and Environmental Health (CEEH) Native TEACH Project.

New center to use novel method to screen chemicals’ toxicity

In-vitro, 3-D chip approach will enable faster evaluation and reduce need for animal models.
Scientists prepare cell cultures to 
test chemicals for their potential 
risk to humans. 

Tens of thousands of chemicals are currently in use, with more introduced every year. Scientists, however, have discerned the toxicity of only a fraction of these because the traditional method of testing is time- and cost-prohibitive – thus the need for better mechanisms to screen chemicals for potential health impacts.
The Environmental Protection Agency today said that it would provide $6 million in seed funds for a Predictive Toxicology Center at the University of Washington – one of three such facilities identified. It is intended to enable researchers to develop more accurate, higher capacity in vitro models – organ-mimicking cell cultures – to test chemicals' potential risk to humans.
Elaine Faustman and Terrance Kavanagh will co-direct the new center.
 “This research is important for establishing novel methods that reflect the complexity of biological systems, yet allow us to evaluate the large number of new chemicals for their potential health impacts before they are put on the market,” said Elaine Faustman. She and Terrance Kavanagh, both UW professors of environmental and occupational health sciences, will co-direct the new center. 
“These systems can help reduce the need for animal models while better replicating and more faithfully mimicking what happens in the human body, including differences in genetics and susceptibility” Kavanagh said. 
Researchers from the Schools of Public Health, Pharmacy, and Medicine will collaborate to develop these three-dimensional cell cultures for the kidney, liver, lung and testis to better model how a person would respond to a chemical exposure. 

A hallmark of the center’s research will be microfluidic chip technology developed by Nortis, a biotech founded by former UW faculty. Less than half the size of an index card, the microfluidic chip offers a platform for cells to be seeded onto the device, which then serves as a unique growing environment and can be connected with the other devices for each organ system, mimicking human circulation.

After validating the three-dimensional cell cultures using known chemical toxicants, researchers will investigate biomarkers of cell injury or altered function that indicate an adverse outcome from an exposure to chemicals for which insufficient data exists. 
Elijah Weber, Department of Pharmaceutics
Graduate students in the School of Pharmacy demonstrate how constant flowing media will go through microphysiological systems connected to pumps outside an incubator.
They will then use modeling techniques to assess and predict human health risks, linking laboratory data with human-exposure pathways.
Testing metals and metal-based nanomaterials will be a focus of the center. 

“There’s been a lot of interest in the biomedical field to use nanomaterials as therapeutics and bioimaging agents,” Kavanagh said, but their unintentional impacts in the general population are less well studied.
For example, inhalation is a primary route of exposure to nanomaterials, so developing a lung system is especially relevant, said William Altemeier, UW associate professor of pulmonary and critical care medicine. He will lead the center's lung cell culture development.  
Faustman will lead the testing of adverse reactions in testicular development and reproduction. Kavanagh will co-manage the liver-testing model with David Eaton, professor of environmental and occupational health sciences. Edward Kelly, UW associate professor in of pharmaceutics (Pharmacy), will manage the kidney cell culture project.
Read the full news release about the Predictive Toxicology Center.

--Elizabeth Sharpe

Meet new CEEH member Dr. Anne Manicone

The CEEH Career Development and Mentoring Core welcomed Dr. Anne Manicone as a junior investigator early this year. Anne is an Assistant Professor in the Department of Medicine, Division of Pulmonary and Critical Care. She will join the CEEH Cardiopulmonary & Metabolic Disease Collaborative Research Team (CRT) headed by Drs. Mike Rosenfeld and William AltemeierAnne presented her research at the monthly CEEH Breakfast Club on January 28 in an informal talk titled Regulation of Macrophage Polarization: Implications in Lung Injury and Repair. She is currently focused on the role of MMP28 in regulating macrophage influx and activation, and the role of macrophage subpopulations in regulating lung injury and its resolution.

More specifically, Anne is characterizing the role of matrix metalloproteinase 28 (MMP28) in regulating the inflammatory response to tobacco smoke-induced emphysema in a mouse model. MMPs comprise a family of extracellular proteinases that function in various processes of innate immunity. MMP28 is one of the newest members of this family, and it is expressed by both macrophages and epithelial cells. Her work suggests that MMP28 inhibits inflammation and promotes reparative macrophage function. In her preliminary studies, MMP28 was shown to be protective in chronic emphysema from cigarette smoke; and her hypothesis is that this is mediated by MMP28-dependent effects on macrophage polarization.  Ongoing work is aimed at uncovering the mechanism and substrates by which MMP28 functions. 

Dr. Manicone's work is pertinent to Chronic Pulmonary Obstructive Disease (COPD) and pulmonary fibrosis, conditions brought on by environmental exposures such as smoking, asbestos, and air pollution, as well as asthma and genetics. Anne indicates she is always interested in collaborations.

The Career Development and Mentoring Core (CDMC), directed by Mike Rosenfeld, works to ensure that the University of Washington recruits, supports, and retains for DEOHS and other Center-affiliated departments (Epidemiology, Genome Sciences, Pharmaceutics), a new generation of high-caliber EHS-focused investigators with a strong interest in gene-environment interactions. The CDMC provides mentorship to new and current CEEH junior faculty to ensure they achieve their full potential as scientists, teachers, and communicators, as well as provides unique career development opportunities and resources to advance their environmental science careers by incorporating a gene-environment approach into their research projects.                                                                                              

                                                                                - Marilyn Hair

Event Highlight: Third Annual Center Research and Public Engagement Awards

The 2014 Annual CEEH Awards for Innovations in Research and Public Engagement were presented at the Annual Center Retreat on December 3rd. 

The Innovations in Research Award recognizes the author or authors of a single, high-impact publication supported by CEEH and celebrates ground-breaking research that furthers the CEEH mission of building capacity, facilitating collaboration through communication, and inspiring creativity, which promotes innovative research, engages stakeholders, and launches the next generation of research and ecogenetics (gene-environment interactions) researchers.

The 2014 Innovations in Research Award went to Ed Kelly and co-authors Zhican Wang, Jenna Voellinger, Cathy Yeung, Danny Shen, Kenneth Thummel, Ying Zheng, Giovanni Ligresti, Dave Eaton, Kimberly Muczynski, Jeremy Duffield, Thomas Neumann, Anna Tourovskaia, Mark Fauver, Greg Kramer, Elizabeth Asp, and Jonathan Himmelfarb for their paper "Innovations in preclinical biology: ex vivo engineering of a human kidney tissue micro perfusion system" published in Stem Cell Research and Therapy.

Kidney disease affects more than 20 million adults in the US, yet little is understood about the impact of kidney disease on drug disposition. There is a need for improved understanding of drug efficacy, safety, and toxicity, especially during drug development. Kelly and his team plan to model the human kidney tubule interstitium using a 3-dimensional modular microphysiological system using cells derived from the human kidney. This system is intended to accurately reflect human physiology, allowing the researchers to predict how the kidneys handle drug disposition, and to assess kidney injury and the biological response to injuries caused by toxicants from both within and outside the body.

The Public Engagement Award recognizes an individual or team for creative, innovative, and meaningful work with communities beyond the university.

The 2014 Public Engagement Award went to PhD candidate Lorelei Walker for her creative and informative 3-minute video, “Engaging Epigenetics: A Tool for Stakeholder Education”, funded in part by the CEEH Community Outreach and Engagement Core (COEC). 

Lorelei's animated video describes epigenetics as the process that regulates our genes. All our cells have the same DNA: Our brain, skin, and white blood cells are different because epigenetics turns different genes on and off in different types of cells. If this epigenetic system is altered, genes can be turned on and off in the wrong cells or at the wrong time. 

Some chemicals can change our epigenetics and how our genes are regulated. The video uses pesticides, BPA and air pollutants as examples of chemicals that can remove gene regulators, and with excessive exposure, make us more vulnerable to getting sick. 

The video concludes by encouraging viewers to avoid BPA and foods with high pesticide residues, be informed voters, and to advocate for a healthier environment for ourselves and our children. 

Congratulations to Ed Kelly and team, and to Lorelei Walker. Keep up the great work!

--Marilyn Hair

Native Environmental Health Stories Project at the University of Washington

Native TEACH tribal researchers gather around Tribal Liaison Valerie Segrest (seated, center)
The Center for Ecogenetics and Environmental Health (CEEH) at the University of Washington in Seattle partnered with the Southwest Environmental Health Sciences Center (SWEHSC) at the University of Arizona for the Native Environmental Health Stories project, a supplement grant from the National Institute of Environmental Health Sciences (NIEHS). The activities at the UW CEEH were a continuation of its Native TEACH (Tradition, Environment And Community Health) Project that began in 2009.

The purpose of the original Native TEACH project was to identify the core concepts of Native environmental health science, as distinct from the mainstream western understanding of environmental health science. The current project was based on what was learned previously about Tribal members’ knowledge, beliefs and understandings of human interactions with their environment, and the value of traditional storytelling as a way to communicate complicated ideas.

CEEH hired a Tribal Liaison, Ms. Valerie Segrest, to lead the project. Valerie is an enrolled member of the Muckleshoot Indian Tribe whose reservation is located south of Seattle at the base of Mt. Rainier. She is a native foods educator and community nutritionist.

Ms. Segrest invited seven Native researchers from six Washington Tribes to attend a kickoff meeting at the University of Washington. The group learned about the Native Environmental Health Stories Project, participated in group exercises about environmental health, and brainstormed what groups in their tribal communities to bring together to talk about the question: What does environmental health mean in our community?

Over the next month, the researchers led conversations in their own tribal communities, which included Chinook, Muckleshoot, Lower Elwha S’Klallam, Port Gamble S’Klallam, Puyallup, Spokane and Yakima. The conversations took place in a tribal college class, Mom’s group, Team Teach, and an artists’ panel at a public art show.

These are some of the products that grew out of the tribal community conversations:

A public Art Exhibit, “Freeing the River”, was held at the Lower Elwha S’Klallam Tribe Heritage Center and featured four Lower Elwha tribal artists who displayed works based on the removal of two 100-year-old dams on the Elwha River. Restoring the Elwha River to its natural flow has helped restore historic salmon runs.

Native TEACH researcher and Lower Elwha S’Klallam tribal member Roger Fernandes, said, “I was taught that the salmon is the source of life for all beings, animals, plants, and the earth itself. The spirit of the salmon and the Salmon People allow us to live a life of abundance and gratitude. The art I have included in this show focus on the salmon and the return of the salmon with the removal of the dams. I was taught that the Elwha River was dammed against the wishes of the Lower Elwha S’Klallam people and that they have been fighting for the removal of the dams for several decades. Because the dams had no fish ladders, they were designed to essentially destroy the wild salmon runs. Because of the work of many of our ancestors and elders we have seen the dams removed and the salmon’s return. Life is in order again.” Photos of the art and a summary of the art show can be found on the CEEH blog

The Native TEACH researcher from the Port Gamble S’Klallam Tribe, Tleena Ives, is involved with a home visiting grant for expectant and new moms. Ms. Ives held her community conversation with the Mom’s group. She collected quotes from the moms and created a children’s book, t̕aʔt̕ə́wəsnaʔ in the S'Klallam language. 

The story goes like this: “You are a Star, This is my wish for you. This is my dream. This is my hope.” Tleena says that the conversation and the children’s book “helps bring power to our people, keeps our traditions alive, highlights what’s important and what we value, and what we want to pass on.” CEEH will publish the children’s book to share with the families in the Mom’s group and with the tribal Head Start families. Tleena and the Mom’s group have generously offered to share the children’s book with CEEH.

The Native TEACH researchers also created two overarching products to summarize the Native Environmental Health Stories project: 

  •  A 10-minute Native TEACH Digital Story. Each of the researchers is interviewed in their home setting talking about their research and the projects they created, one of which is an original song featured in the video.  
  • A year-long calendar blog posted month by month. Each month focuses on a tribal community and includes 4 topics: An Environmental Health Challenge, Community Art Project, Traditional Food, and a Call to Action. A new blogpost appears each week. 
The CEEH Community Outreach and Engagement Core (COEC) looks forward to future collaborations with our new tribal partners.
--Marilyn Hair

Event Highlight: The Living Breath of Wǝɫǝbʔaltxʷ Symposium

Huckleberries are a traditional food of Northwest Tribes
  The Center for Ecogenetics & Environmental Health was a sponsor of the UW American Indian Studies Department 2nd Annual Symposium, The Living Breath of Wǝɫǝbʔaltxʷ. The symposium was held Sept 26-27 at the UW Center for Urban Horticulture.

  Wǝɫǝbʔaltxʷ (listen) is a Lushootseed word that means Intellectual House. The conference title honors the Wǝɫǝbʔaltxʷ that UW is building on campus, the culmination of a 40-year dream of the Native community. Phase One of the Wǝɫǝbʔaltxʷ, a longhouse-style building that pays homage to the Coast Salish culture and architecture, is scheduled to open in February 2015. The Wǝɫǝbʔaltxʷ exemplifies the spirit of sharing, cooperation and commitment to indigenous knowledges and local and national indigenous communities. The symposium showcased the kind of work that will be done in this new space.

   The Living Breath of Wǝɫǝbʔaltxʷ symposium began by acknowledging the Duwamish tribe on whose traditional land we were meeting. Next came the Opening Prayer with drum accompaniment and Welcome Song by the Nuu-chah-nulth singers of Vancouver Island, BC. Two young Nuu-chah-nulth children from the tribal school joined their teacher who led the Welcome Song. Many challenges and disparities remain, but here is a victory: A Native teacher in a tribal elementary school teaches tribal children their language, songs, and cultural traditions.

   A team of presenters told about the Swedafzali or "place of mountain huckleberries" (Lushootseed), a 2-square mile plot of land at 5000 feet elevation in the Mount Baker/Snoqualmie National Forest. The land belonged to Weyerhaueser, and the lumber company clear cut the trees and and subsequently donated the plot to the US Forest Service (USFS). Through a partnership between the Tulalip Tribe and USFS, the tribe is restoring the land and planting mountain huckleberries, which are the most pure and medicinal when grown at high elevation. The damaged land is recovering, the huckleberries are profuse, and families are coming to gather. Some tribal members want to camp overnight. Next will be a campsite and rules to preserve the habitat, and negotiating the right to do traditional burning to keep encroaching trees off the huckleberry meadow. Native gathering rights off the reservation are guaranteed in the 1855 Treaty of Point Elliott between the US Government and Coast Salish tribes. This partnership improves the tribe's access to traditional food.

   Another panel discussed whaling culture and food access. Prof. Charlotte Coté (Tseshaht/Nuu-chah-nulth) and Micah McCarty (Makah), special assistant to President Obama for tribal and government relations at Evergreen State College, told of their tribes' whaling culture and nearly a century in which they have lacked access to whale meat and blubber. When Charlotte Coté told her mentor at UC-Berkeley that she wanted to write her dissertation about native culture, the mentor told her to study the Navajo. Instead she went home and talked to her relatives and tribal elders and decided to study the Nuu-chah-nulth whaling culture. Her dissertation is available here: Spirits of our Whaling AncestorsMcCarty reported that the Makah Tribe conducted one gray whale hunt, in 1999, an event of international significance. The right of the Makah tribe to hunt whale has been tied up in court since 2004.

    An audience member reported that the sockeye run is abundant this year, but the fish are too large. He said the small fry are eating fish food that spills through the nets on fish farms, and more of the fry survive, but they grow too fast and they eat the wrong food. Even a success story has a shadow side.

   Symposium attendees were served meals featuring traditional foods. We enjoyed strawberries, blueberries, raspberries, apples, and dense, seed-filled muffins; salmon, huckleberries, wild rice, and elk jerky. I noticed there were no bananas at breakfast. And I missed dessert. It hit home which foods were local and which weren't available or, like dairy, weren't part of a traditional diet. But the large urn of coffee? It was popular, but was that traditional?

   The event continued Saturday when our collaborator on the Native TEACH project, Valerie Segrest, coordinator of the Muckleshoot Food Sovereignty Project,  participated in the panel on Northwest Tribal Food Sovereignty.

   Discussions helped spread awareness about the issue of food sovereignty and food security. Planning Committee chair Charlotte Coté reported, “It’s a coming together of people who have an interest in traditional indigenous foods, sharing stories, ideas, and strategies about how we can protect those foods.” It was The Living Breath of Wǝɫǝbʔaltxʷ.
    See our Factsheets about Indigenous Cultural Autonomy and Responsible Research Partnerships with Indigenous Communities and read an article about the Living Breath Conference in the UW Daily

 -- Marilyn Hair