From VU: “VU scientists report a way to calm the sepsis ‘storm’ ”

Vanderbilt U Bloc

Vanderbilt University

Jun. 22, 2017
Bill Snyder
william.snyder@Vanderbilt.Edu
(615) 322-4747

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From left, Ruth Ann Veach, Pierre Antony, Ph.D., a visiting scientist from France, Jozef Zienkiewicz, Ph.D., Jacek Hawiger, M.D., Ph.D., Yan Liu, M.D., and Lukasz Wylezinski, Ph.D., contributed to the sepsis study.

Researchers at Vanderbilt University Medical Center (VUMC) have found a way to calm the “genomic storm” that triggers the often-lethal consequences of sepsis.

Sepsis, an exaggerated and overwhelming inflammatory response to various infections, is a leading cause of death in the United States and around the world.

Using a cell-penetrating peptide they developed, the researchers suppressed in an animal model of polymicrobial sepsis the transport of pro-inflammatory transcription factors into the cell’s nucleus. That, in turn, prevented activation of inflammatory pathways and reduced resulting blood vessel damage, respiratory distress, multiple organ failure and death.

Their findings, reported this week in the online journal PLOS ONE, highlight the potential benefit of targeting nuclear transport as an adjunctive therapy in the management of sepsis.

“Sepsis is fast and furious, especially among the youngest and oldest patients,” said senior author Jacek Hawiger, M.D., Ph.D., the Louise B. McGavock Professor, Distinguished Professor of Medicine and professor of Molecular Physiology and Biophysics at Vanderbilt.

“We hope that this new treatment will prove safe and effective not only in increasing survival but also reducing serious complications in survivors of sepsis,” said Hawiger, who also is a research health scientist at the Nashville Veterans Affairs Medical Center.

After his mother succumbed to sepsis, Hawiger was determined to find better ways to control and prevent it.

One way to restore physiologic barriers to sepsis and other inflammatory diseases is to deliver anti-inflammatory peptides and proteins across the cell membrane. During the past 20 years, Hawiger and his colleagues have pioneered platforms for doing so.

In the current study, they tested a peptide called a Nuclear Transport Modifier or NTM in an animal model of sepsis caused by spillage of the gut’s microbes into the bloodstream.

NTM not only suppressed production of pro-inflammatory factors but markedly reduced the amount of bacteria in the lungs and bloodstream even before antibiotic therapy was started. Signs of microvascular injury to the lining of tiny blood vessels were attenuated. And when NTM was combined with antibiotic therapy, survival nearly doubled.

“The study of nuclear transport signaling … opens up a new avenue for exploring innovative approaches to restore the complex balance of pro- and anti-inflammatory mechanisms in blood and vascular systems that would allow for successful recovery from sepsis,” the researchers concluded.

Ruth Ann Veach, research instructor in the Division of Nephrology, is first author. Co-authors include Yan Liu, M.D., Jozef Zienkiewicz, Ph.D., Lukasz Wylezinski, Ph.D., Kelli Boyd, Ph.D., DVM, and James Wynn, M.D.

The study was supported in part by National Institutes of Health grants DK058404, CA068485 and TR002243 and by a Veterans Affairs Merit Review Award.

See the full article here .

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Commodore Cornelius Vanderbilt was in his 79th year when he decided to make the gift that founded Vanderbilt University in the spring of 1873.

The $1 million that he gave to endow and build the university was the commodore’s only major philanthropy. Methodist Bishop Holland N. McTyeire of Nashville, husband of Amelia Townsend who was a cousin of the commodore’s young second wife Frank Crawford, went to New York for medical treatment early in 1873 and spent time recovering in the Vanderbilt mansion. He won the commodore’s admiration and support for the project of building a university in the South that would “contribute to strengthening the ties which should exist between all sections of our common country.”

McTyeire chose the site for the campus, supervised the construction of buildings and personally planted many of the trees that today make Vanderbilt a national arboretum. At the outset, the university consisted of one Main Building (now Kirkland Hall), an astronomical observatory and houses for professors. Landon C. Garland was Vanderbilt’s first chancellor, serving from 1875 to 1893. He advised McTyeire in selecting the faculty, arranged the curriculum and set the policies of the university.

For the first 40 years of its existence, Vanderbilt was under the auspices of the Methodist Episcopal Church, South. The Vanderbilt Board of Trust severed its ties with the church in June 1914 as a result of a dispute with the bishops over who would appoint university trustees.

kirkland hallFrom the outset, Vanderbilt met two definitions of a university: It offered work in the liberal arts and sciences beyond the baccalaureate degree and it embraced several professional schools in addition to its college. James H. Kirkland, the longest serving chancellor in university history (1893-1937), followed Chancellor Garland. He guided Vanderbilt to rebuild after a fire in 1905 that consumed the main building, which was renamed in Kirkland’s honor, and all its contents. He also navigated the university through the separation from the Methodist Church. Notable advances in graduate studies were made under the third chancellor, Oliver Cromwell Carmichael (1937-46). He also created the Joint University Library, brought about by a coalition of Vanderbilt, Peabody College and Scarritt College.

Remarkable continuity has characterized the government of Vanderbilt. The original charter, issued in 1872, was amended in 1873 to make the legal name of the corporation “The Vanderbilt University.” The charter has not been altered since.

The university is self-governing under a Board of Trust that, since the beginning, has elected its own members and officers. The university’s general government is vested in the Board of Trust. The immediate government of the university is committed to the chancellor, who is elected by the Board of Trust.

The original Vanderbilt campus consisted of 75 acres. By 1960, the campus had spread to about 260 acres of land. When George Peabody College for Teachers merged with Vanderbilt in 1979, about 53 acres were added.

wyatt centerVanderbilt’s student enrollment tended to double itself each 25 years during the first century of the university’s history: 307 in the fall of 1875; 754 in 1900; 1,377 in 1925; 3,529 in 1950; 7,034 in 1975. In the fall of 1999 the enrollment was 10,127.

In the planning of Vanderbilt, the assumption seemed to be that it would be an all-male institution. Yet the board never enacted rules prohibiting women. At least one woman attended Vanderbilt classes every year from 1875 on. Most came to classes by courtesy of professors or as special or irregular (non-degree) students. From 1892 to 1901 women at Vanderbilt gained full legal equality except in one respect — access to dorms. In 1894 the faculty and board allowed women to compete for academic prizes. By 1897, four or five women entered with each freshman class. By 1913 the student body contained 78 women, or just more than 20 percent of the academic enrollment.

National recognition of the university’s status came in 1949 with election of Vanderbilt to membership in the select Association of American Universities. In the 1950s Vanderbilt began to outgrow its provincial roots and to measure its achievements by national standards under the leadership of Chancellor Harvie Branscomb. By its 90th anniversary in 1963, Vanderbilt for the first time ranked in the top 20 private universities in the United States.

Vanderbilt continued to excel in research, and the number of university buildings more than doubled under the leadership of Chancellors Alexander Heard (1963-1982) and Joe B. Wyatt (1982-2000), only the fifth and sixth chancellors in Vanderbilt’s long and distinguished history. Heard added three schools (Blair, the Owen Graduate School of Management and Peabody College) to the seven already existing and constructed three dozen buildings. During Wyatt’s tenure, Vanderbilt acquired or built one-third of the campus buildings and made great strides in diversity, volunteerism and technology.

The university grew and changed significantly under its seventh chancellor, Gordon Gee, who served from 2000 to 2007. Vanderbilt led the country in the rate of growth for academic research funding, which increased to more than $450 million and became one of the most selective undergraduate institutions in the country.

On March 1, 2008, Nicholas S. Zeppos was named Vanderbilt’s eighth chancellor after serving as interim chancellor beginning Aug. 1, 2007. Prior to that, he spent 2002-2008 as Vanderbilt’s provost, overseeing undergraduate, graduate and professional education programs as well as development, alumni relations and research efforts in liberal arts and sciences, engineering, music, education, business, law and divinity. He first came to Vanderbilt in 1987 as an assistant professor in the law school. In his first five years, Zeppos led the university through the most challenging economic times since the Great Depression, while continuing to attract the best students and faculty from across the country and around the world. Vanderbilt got through the economic crisis notably less scathed than many of its peers and began and remained committed to its much-praised enhanced financial aid policy for all undergraduates during the same timespan. The Martha Rivers Ingram Commons for first-year students opened in 2008 and College Halls, the next phase in the residential education system at Vanderbilt, is on track to open in the fall of 2014. During Zeppos’ first five years, Vanderbilt has drawn robust support from federal funding agencies, and the Medical Center entered into agreements with regional hospitals and health care systems in middle and east Tennessee that will bring Vanderbilt care to patients across the state.

studentsToday, Vanderbilt University is a private research university of about 6,500 undergraduates and 5,300 graduate and professional students. The university comprises 10 schools, a public policy center and The Freedom Forum First Amendment Center. Vanderbilt offers undergraduate programs in the liberal arts and sciences, engineering, music, education and human development as well as a full range of graduate and professional degrees. The university is consistently ranked as one of the nation’s top 20 universities by publications such as U.S. News & World Report, with several programs and disciplines ranking in the top 10.

Cutting-edge research and liberal arts, combined with strong ties to a distinguished medical center, creates an invigorating atmosphere where students tailor their education to meet their goals and researchers collaborate to solve complex questions affecting our health, culture and society.

Vanderbilt, an independent, privately supported university, and the separate, non-profit Vanderbilt University Medical Center share a respected name and enjoy close collaboration through education and research. Together, the number of people employed by these two organizations exceeds that of the largest private employer in the Middle Tennessee region.
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