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True Sioux Hope Foundation, ASU partner to offer Native students a big boost

ASU, True Sioux partnership gives 2 Native students chance for college degree
July 21, 2017

Scholarships for two new Sun Devils part of nascent alliance to strengthen community on economically hard-hit Pine Ridge Reservation

Last April, Mariah McGhee had resigned herself to the fact that college wasn’t in the cards.

McGhee, a class valedictorian who had often visited Arizona, had dreamed of attending Arizona State University since she was 5. But McGhee (pictured above with her mom) knew her family couldn’t afford out-of-state tuition, and she was adamant about not racking up personal debt through student loans. The 18-year-old was prepared to start her work career without a degree.

Then a miracle dropped in her lap: a full four-year scholarship to ASU.

“It wasn’t just a surprise but a real shock,” said McGee, who graduated from Red Cloud High School on the Pine Ridge Indian Reservation in South Dakota. “When they brought me into the principal’s office to give me some news, I thought I was in trouble.”

Savannah Jacobs
Savannah Jacobs (pictured with her father, Chuck Jacobs, at their home on the Pine Ridge Indian Reservation in South Dakota) is one of the two students sponsored by True Sioux Hope Foundation. She will study political science at ASU. Her plan is to get her degree and then “come back to Pine Ridge and help in the fight” to improve lives there. Photo by Deanna Dent/ASU Now

When McGhee arrived, she also encountered classmate Savannah Jacobs, who also thought she was in trouble. After a few suspenseful moments, they were told to pack their bags because they were headed to ASU.

“We both cried and had tears streaming down our faces. It was a huge gift,” recalled Jacobs, who plans on majoring in political science. McGee said she will study business entrepreneurship at W. P. Carey School of Business.

Their scholarships are a result of a new initiative between the ASU FoundationFormed in 2014, the True Sioux Hope Foundation is a nonprofit organization aimed at combating poverty, improving education and creating sustainable organizations for the Oglala Lakota Sioux Tribe on the Pine Ridge Reservation., the Center for Indian Education and the True Sioux Hope Foundation, which is sponsoring a pair of Native students from Pine Ridge to attend ASU.

“Given who we are as an institution, with a charterASU’s charter reads: “ASU is a comprehensive public research university, measured not by whom we exclude, but rather by whom we include and how they succeed; advancing research and discovery of public value; and assuming fundamental responsibility for the economic, social, cultural and overall health of the communities it serves.” that clearly outlines our work in being inclusive, interested in how our students succeed, and that we assume responsibility for people and society, this opportunity is perfect for us,” said Bryan Brayboy, ASU special adviser to the president and President’s Professor of indigenous education and justice. “We want to partner with Pine Ridge in order to help them define and enact their future. This starts, in part, with Mariah and Savannah.”

Brayboy added that ASU is an excellent place for McGhee and Jacobs to seek their higher education as the university will welcome more than 2,700 indigenous students this fall and is responsible for 20 percent of the nation’s American Indian doctoral students.

Twila True
True Sioux Hope Foundation founder Twila True addresses the crowd and thanks them for coming to see their programs at Pine Ridge. Photo by Deanna Dent/ASU Now

That’s one of the reasons why True Sioux Hope Foundation leader Twila True partnered with ASU.

“They got a whisper of what we were trying to do and said, ‘Tell us more,’” said True, a philanthropist, entrepreneur, and co-founder and CEO of True Investments, a real estate private equity firm based in Newport Beach, Calif., where True resides.

As a youngster, True was whisked to California from Pine Ridge as part of the Indian Relocation Act of 1956, a federal program intended to encourage Native Americans to leave Indian reservations to acquire vocational skills and assimilate into the general population throughout the 1950s and 1960s.

Today True is a successful businessperson, but she never forgot her roots.

“The Pine Ridge Reservation has always had a place in my heart,” True said. “I had tribe, I had family and I had culture.”

True also wants to change part of their culture — the one that gets the most ink these days.

Pine Ridge is considered the most economically disadvantaged reservation in the United States with a 90 percent unemployment rate and average annual household income of $3,500. The student dropout rate is over 70 percent, and the teacher turnover rate is eight times higher than that of the U.S. national average.

“You can’t affect change unless it’s long-term,” True said regarding the scholarships. “We’re all parents now. True Sioux Hope and ASU are now parents of these girls, and we’re going to take them and graduate them from college.”

That was a sentiment echoed by the ASU Foundation.

“Through our partnership with the True Sioux Hope Foundation and the Pine Ridge Indian Reservation, we believe we can work together to rebuild and strengthen capacity in this culturally rich community while ensuring a positive impact for future generations,” said Gretchen Buhlig, CEO of ASU Foundation, the independent nonprofit that raises and invests private donations in support of ASU.

The two scholarships are just the beginning of the partnership. Although details are still being ironed out, there are plans afoot for ASU to help rebuild and strengthen the capacity of Pine Ridge. Brayboy says this will be done through education, housing, economic development, and health and well-being initiatives created by ASU and True Sioux Hope to ensure positive impact for generations to come. He was quick to point out that this is all happening in partnership with and at the direction of the Pine Ridge community, and he hopes that it will become a model for other universities and entities looking to boost other tribal communities throughout the country.

McGhee and Jacobs said it’s already having an impact on their lives. The two have vowed they'll return to the reservation after graduation and use their education to improve the lives of others. McGhee wants to start a business there while Jacobs would like to start a fund or organization to enable Native students like herself to go to college.

“The goal is to get a college degree from ASU, come back to Pine Ridge and help in the fight,” Jacobs said.

 

Top photo: True Sioux Hope Foundation scholarship recipient Mariah McGhee (right) and her mother, Donna McGhee, pose for a portrait on the Pine Ridge Indian Reservation on July 7. McGhee plans to study business entrepreneurship at ASU. Photo by Deanna Dent/ASU Now

Reporter , ASU Now

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July 24, 2017

Findings of team led by ASU scientists offer hope for therapies targeting cell loss in the brain, an inevitable and devastating outcome of Alzheimer’s progression

Alzheimer’s disease tragically ravages the brains, memories and, ultimately, personalities of its victims. Now affecting 5 million Americans, Alzheimer’s disease is the sixth-leading cause of death in the U.S., and a cure for Alzheimer’s remains elusive, as the exact biological events that trigger it are still unknown.

In a new study published today, Arizona State University-Banner Health neuroscientist Salvatore Oddo and his colleagues from Phoenix’s Translational Genomics Research Institute (TGen) — as well as the University of California, Irvine, and Mount Sinai in New York — have identified a new way for brain cells to become fated to die during Alzheimer’s disease.

The research team has found the first evidence that the activation of a biological pathway called necroptosis, which causes neuronal loss, is closely linked with Alzheimer’s severity, cognitive decline and extreme loss of tissue and brain weight that are all advanced hallmarks of the disease.

“We anticipate that our findings will spur a new area of Alzheimer’s disease research focused on further detailing the role of necroptosis and developing new therapeutic strategies aimed at blocking it,” said Oddo, the lead author of this study, and scientist at the ASU-Banner Neurodegenerative Disease Research Center at the Biodesign Institute and associate professor in the School of Life Sciences.

The findings appear in the advanced online edition of Nature Neuroscience.

Necroptosis, which causes cells to burst from the inside out and die, is triggered by a triad of proteins. It has been shown to play a central role in multiple sclerosis and Lou Gehrig’s disease (amyotrophic lateral sclerosis, or ALS), and now for the first time, also in Alzheimer’s disease.

“There is no doubt that the brains of people with Alzheimer’s disease have fewer neurons,” said Oddo. “The brain is much smaller and weighs less; it shrinks because neurons are dying. That has been known for 100 years, but until now, the mechanism wasn’t understood.”

Links with Alzheimer’s

Necroptosis was first identified as a result of inflammation, a common malady in Alzheimer’s.

Three critical proteins are involved in the initiation of necroptosis, known as RIPK1, RIPK3 and MLKL. The study describes a key event in the process of necroptosis when RIPK1 and RIPK3 form a filamentous structure known as the necrosome.

The formation of the necrosome appears to jump-start the process of necroptosis. It activates MLKL, which affects the cell’s mitochondria, eventually leading to cell death.

Winnie Liang, TGen assistant professor, director of TGen Scientific Operations and director of TGen's Collaborative Sequencing Center, said MLKL executes necroptosis to ultimately cause cell death.

“In this study, we show for the first time that necroptosis is activated in Alzheimer’s disease, providing a plausible mechanism underlying neuronal loss in this disorder,” said Liang, who contributed to the study’s gene expression analyses.

 

To explore necroptosis, the research team utilized multiple cohorts of human samples obtained from the Brain and Body Donation Program at the Banner Sun Health Research Institute and Mount Sinai VA Medical Center Brain Bank.

First, they measured RIPK1, RIPK3 and MLKL in a specific region of the brain that is typically ravaged by cell loss during the advance of Alzheimer’s disease — the temporal gyrus. Results showed that during necroptosis, these markers were increased in the brains of people with Alzheimer’s disease.

Next, they identified the molecular cascade of necroptosis activation, with RIPK1 activating RIPK3 by binding with it. This protein complex then binds to and activates MLKL. Analysis of mRNA and protein revealed elevated levels of both RIPK1 and MLKL in the postmortem brain tissues of patients with Alzheimer’s when compared with normal postmortem brains.  

Furthermore, they also demonstrated that necroptosis activation correlated with the protein tau. Intriguingly, necroptosis did not appear to be linked with the other chief physiological characteristic of Alzheimer’s pathology, beta-amyloid plaque.

Engines of decline

To assess the relationship between necroptotic protein levels and cognitive health, the study revisited the scores of patients whose postmortem brain tissue was evaluated for necroptosis. Results showed a significant association between RIPK1, MLKL and diminished scores on the Mini-Mental State Examination (MMSE), a widely used test measuring cognitive health.

Given the established relationship between necroptosis and Alzheimer’s pathology, including cell loss and attendant cognitive deficit, the study sought to inhibit the process to study the dynamic effects on cell death and memory loss.

With such experiments not possible in people, the team demonstrated in a mouse model of the disease that lowering the activation of the necroptosis pathway reduces cell loss and improves performance in memory-related tasks, offering new hope for human therapeutics to halt or reverse the effects of Alzheimer’s.

The results reveal that the inhibition of necroptosis activation through the blockage of RIPK1 prevents cell loss in mice. Compellingly, mice with inhibited activation of necroptosis pathways performed significantly better in tests of spatial memory involving navigation through a water maze.

New understanding, new hope

The study opens a new window on Alzheimer’s research and offers hope for therapies targeting cell loss in the brain, an inevitable and devastating outcome of Alzheimer’s progression.

Oddo stresses that RIPK1, RIPK3 and MLKL are among many potential drug targets, and others will likely follow as the links between necroptosis and Alzheimer’s become clearer. While multiple causes of the disease are likely, understanding more clearly all targets that trigger disease will offer the best hope since neuronal loss has been found in people more than a decade before any symptoms of dementia.

“One may not agree as to which molecules trigger Alzheimer’s disease, ” said Oddo, “but everybody agrees that the end result is the neuronal loss. If you can prevent that you may have a beneficial effect.” 

This work was supported by grants from the Arizona Alzheimer’s Consortium and the National Institutes of Health (R01 AG037637) to Salvatore Oddo, and R01 NS083801 and P50 AG016573 to Kim Green.

Data for the RIPK1 causal regulatory gene network were generated from postmortem brain tissue collected through the Mount Sinai VA Medical Center Brain Bank and were provided by Dr. Eric Schadt from Mount Sinai School of Medicine. The computational resources and staff expertise provided by the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai also contributed to the performance of this research.

Joe Caspermeyer

Managing editor , Biodesign Institute

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