Tagged: Vanderbilt U Toggle Comment Threads | Keyboard Shortcuts

  • richardmitnick 10:56 am on June 13, 2017 Permalink | Reply
    Tags: Aortic valve stenosis, Cadherin-11, Calcification of heart valves, Rheumatoid arthritis, Vanderbilt U   

    From Vanderbilt: “Drug developed for arthritis could be first to stop heart valve calcification” 

    Vanderbilt U Bloc

    Vanderbilt University

    Jun. 12, 2017
    Heidi Hall

    The first drug to treat calcification of heart valves may be one originally designed for rheumatoid arthritis.

    Today in Circulation, the journal of the American Heart Association, Vanderbilt University researchers published findings that the drug – a monoclonal antibody known as SYN0012 – shows promise in keeping heart valve leaflets supple. About a quarter of Americans suffer hardening of the valves by age 65 and about half by 85, and the only treatment is surgical replacement.

    The culprit in the condition, called aortic valve stenosis, is cadherin-11, a binding protein necessary for normal wound healing. Fibroblasts, the most common cell in connective tissue, produce it to ensure cuts and broken bones reconnect, and heart valves are composed of this type of cell. As hearts age and lose elasticity, the fibroblasts become overactive, producing mass amounts of cadherin-11 until the three thin leaflets that make up aortic valves become virtually immobile. The heart pumps harder in an attempt to push blood through the valve, causing the chambers of the heart to enlarge, leading to heart failure if the valve isn’t replaced.

    The rheumatoid arthritis drug, an anti-inflammatory, physically binds to cadherin-11 (CDH-11) on the surface of cells so that they can’t bind together.

    “Aortic valve stenosis, even though it involves only a little piece of tissue, has a catastrophic effect on the heart,” said W. David Merryman, associate professor of biomedical engineering. “The antibody we’re working with blocks fibroblasts from becoming the active type that leads to disease. It keeps them from becoming inflamed.

    “We believe there is potential for using this drug at the first sign of valve disease to prevent the progression,” Merryman said. “You likely cannot reverse the damage, but we believe the drug can prevent it.”

    Common disease claims lives

    About 750,000 Americans per year suffer heart attacks, and those plus all other varieties of heart disease are the No. 1 killers in America.

    Surgeons can replace damaged valves with ones made from either pig or cow tissue or with mechanical versions, said Vanderbilt cardiologist and Assistant Professor of Medicine Mike Baker. Physicians’ only option is to monitor calcifying valves once they’re detected and then operate when symptoms appear, he said.

    “Once the patient becomes symptomatic, they start running a significant risk of heart failure or even death,” Baker said. “The exciting thing about this drug’s potential is that it could allow us to consider a strategy of prevention, as we do with other forms of heart disease – like lowering cholesterol or using ACE inhibitors. We don’t have any interventions for aortic valve stenosis that slow its progression.”

    The drug is in human clinical trials for treatment of rheumatoid arthritis. After those are complete, Merryman hopes to gain permission to run clinical trials for uses in heart valve disease.

    Fluke leads to potential cure

    Merryman’s research into CDH-11 dates back to 2013, when two of his Ph.D. students compared two studies of heart valve cellular responses that came to completely different conclusions. One found that a chemical compound caused valve fibroblasts to become active, similar to what is observed during valve disease, but the other study indicated that the same compound prevented the cells from calcifying, indicating that a key piece of the valve disease puzzle was missing. They realized that the teams behind those studies were inadvertently turning CDH-11 production on and off, affecting the outcome.

    The Ph.D. students obtained heart valves preserved from surgeries at Vanderbilt University Medical Center and found that patients suffering from calcification had, in some cases, 50 times as much CDH-11 present in their valves as patients without the condition. They completed another study that showed a NOTCH1 genetic mutation likely ensured those carrying it eventually would suffer from heart valve disease because it leads to CDH-11 overproduction.

    Merryman’s work is funded by a recent $5.3 million, seven-year R35 Emerging Investigator Award from the National Heart, Lung and Blood Institute. It also funds his research in developing heart valves that may one day be able to grow along with children.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    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.
    Related links

    Advertisements
     
  • richardmitnick 8:06 pm on June 8, 2017 Permalink | Reply
    Tags: , , , Project reveals importance of cancer gene mutation testing, Vanderbilt U   

    From Vanderbilt: “Project reveals importance of cancer gene mutation testing” 

    Vanderbilt U Bloc

    Vanderbilt University

    Jun. 8, 2017
    Dagny Stuart
    Dagny.stuart@vanderbilt.edu

    An international genomic data-sharing consortium has analyzed nearly 19,000 patient genomic records and found that testing of patient tumors for relevant gene mutations often provides a roadmap for the use of effective therapies.

    The American Association for Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (GENIE) is a multi-phase, multi-year data-sharing project launched in 2015 with eight academic centers. Vanderbilt-Ingram Cancer Center (VICC) is one of the institutions that shared de-identified genomic records from patients treated at the center to determine if genome sequencing can identify clinically useful mutations.

    Mia Levy, M.D., Ph.D., Ingram Professor of Cancer Research and director of Cancer Health Informatics and Strategy, and Christine Micheel, Ph.D., research assistant professor of Medicine and managing editor of My Cancer Genome, led the VICC effort. Thomas Stricker, M.D., Ph.D., Michele LeNoue-Newton, Ph.D., and Lucy Wang also served as authors.

    1
    Mia Levy, M.D., Ph.D.

    One of the criticisms of molecular profiling is the time and financial cost involved in testing all patients since relatively small percentages of patients actually have a mutation that can be treated with a specific therapy. To determine the frequency of important mutations, the AACR Project GENIE group mapped all mutations to variant interpretations merged from other knowledge bases, including My Cancer Genome, OncoKB and Personalized Cancer Therapy.

    The new analysis found that more than 30 percent of the patient samples had mutations that are clinically actionable, meaning patients potentially could be treated with targeted therapies already approved by the U.S. Food and Drug Administration (FDA) or which are being tested in clinical trials.

    These frequencies varied widely across disease, from highly recurrent and druggable mutations in gastrointestinal stromal tumors (GIST) — 66 percent, almost all of which were mutations of KIT and PDGFRA associated with standard-of-care therapies — to tumor types with few actionable alterations, such as renal cell, prostate or pancreatic cancer.

    Breast cancer is the disease with the highest fraction of patients who might benefit from existing investigational targeted therapies, due to frequent mutations of AKT1, ERBB2 and PIK3CA, account­ing for 38 percent of patients.

    The investigators anticipate one of the benefits of GENIE will be an increased power for determining the clinical significance of mutations, particularly new indica­tions for approved drugs, as well as data-driven selection of tumors likely to contain actionable mutations for clinical trials.

    The study was supported by funds from the AACR, Genentech, Boehringer Ingelheim, Pfizer, Eli Lilly, the Howard Hughes Medical Institute, the National Institutes of Health, the National Cancer Institute, the Princess Margaret Cancer Foundation, the Ontario Ministry of Health, Susan G. Komen, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the T.J. Martell Foundation, the Commonwealth Foundation, the Cancer Prevention and Research Institute of Texas, the Dutch Ministry of Health, and the Dutch Cancer Society.

    The other seven institutions that participated in AACR Project GENIE phase 1 are: Dana-Farber Cancer Institute, Boston; Gustave Roussy Cancer Campus, Paris-Villejuif, France; The Netherlands Cancer Institute, Amsterdam, on behalf of the Center for Personalized Cancer Treatment, Utrecht, The Netherlands; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore; Memorial Sloan Kettering Cancer Center, New York; Princess Margaret Cancer Centre, Toronto; and University of Texas MD Anderson Cancer Center, Houston.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    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.
    Related links

     
  • richardmitnick 9:19 am on May 17, 2017 Permalink | Reply
    Tags: , , VADL- Vanderbilt Aerospace Design Laboratory, Vanderbilt U   

    From Vanderbilt: “Student rocketeers earn second place in NASA contest” 

    Vanderbilt U Bloc

    Vanderbilt University

    May 12, 2017
    Brenda Ellis
    (615) 343-6314
    Brenda.Ellis@Vanderbilt.edu

    1
    Vanderbilt rocketeers with their High Roller rocket at the NASA Student Launch Competition in Alabama. (Photo: VADL)

    Vanderbilt soars to success with innovative rocket designs and payloads.

    Engineering students from the Vanderbilt Aerospace Design Laboratory earned the second place in the 2017 NASA-Orbital ATK Rocket Challenge. They received a cash prize of $2,500, an award created this year by the National Space Club in Huntsville, Alabama.

    2
    High Roller at takeoff from the launch rail at the NASA launch competition in April. (Photo: Jim Wilkerson)

    For ten straight years, Vanderbilt has soared to success with innovative rocket designs and payloads and this year has been no exception. Having earned more than 20 awards in the past decade, including a record-setting four back-to-back national championships from 2013 to 2016, VADL added the 2017 Payload Design, Rocket Fair Display and Education Engagement awards to their awards collection.

    NASA announced the results of the competition May 12. University of Louisville captured top honors and Cornell University came in third.

    The VADL team developed an ingenious set of cold gas supersonic thrusters to control the roll on their rocket – High Roller – during flight, netting them the prestigious Payload Design Award.

    The payload design was one of three predetermined payload options offered to university teams. The roll induction and counter roll payload required teams to design a system that is capable of controlling a rocket’s roll after motor burnout. After the system has induced two rotations, it requires a counter rolling moment to halt all rolling motion for the remainder of rocket’s ascent.

    “It is extremely noteworthy that VADL’s decade of success has coincided with rapid developments in the private space sector and the admission of extraordinary students to Vanderbilt, who have been able to take on the competitions’ extreme challenges,” said Professor Amrutur Anilkumar, who created the program and directs VADL. “Seven payload design awards and four national championships is proof positive as to what can be achieved at Vanderbilt without a formal department in aerospace engineering.”

    Another testament to VADL’s success: All 2017 seniors in the program seeking jobs are heading to aerospace careers at Lockheed Martin, Space-X, Honeywell Aerospace and other companies. Three seniors start graduate studies at Stanford in the fall.

    The student launch competition is a NASA-conducted and aerospace industry-evaluated engineering design challenge built around a NASA mission. It is an intense eight-month contest involving payload and rocket designs, project reports, design reviews, outreach activities and website design, followed by a grand finale launch in April.

    “The Vanderbilt Aerospace Design Laboratory was set up to provide an opportunity for engineering students, both undergraduate and graduate, to take up the challenge of designing a novel payload and a launch vehicle each year, working through the details starting from fundamental science, through engineering analysis, and eventually leading to technological deliverables,” Anilkumar said.

    “It is a very intense immersion program and a challenge in extreme engineering. What drives the team is the fact that they need to build a demanding vehicle around an innovative payload and test fly it in the field, where everything has to work in a six-eight second experiment window,” he said.

    Building something from scratch is a liberating experience, said Grady Lynch, a 2017 mechanical engineering graduate who is headed to Lockheed Martin as a design engineer.

    “In aerospace engineering form fits function, and there is no room for aesthetics. The modeling and analytical solutions, testing and validation, all meld seamlessly—it is the ultimate engineering,” said Lynch. “One aspect of this program is that the on-pad cost of the rocket should not exceed $5000. This requires that we design, machine and fabricate components all on our own and also undertake rigorous component testing.”

    Michael Gilliland, who will be joining Space-X as a design engineer, said detailed analysis and risk mitigation for both the rocket and the payload were at the top of the team’s agenda.

    “Generally, subsystems that function in normal gravity conditions are exposed to extreme loads at 15g takeoff and unexpected failures can happen. To anticipate these failures and take preemptive actions, and to set up backup protocols for minimum deliverable data, was the focus of our training,” Gilliland said.

    “Ground-based testing and validation is a key component, while the flight is the ultimate challenge. Building robust platforms for checking out rocket roll control through cold gas thrusters has been most rewarding,” said Artie Binstein. He is heading to Stanford University for graduate school where he plans to study space flight dynamics and controls.

    “Simulating rocket flight and incorporating the effects of atmospheric wind gusts with an overlay of rotation control has been a very practical validation of complex analytical tools. We have been able to predict rocket performance to a high precision,” said Paul Register, who also is heading to Stanford for graduate studies in aerospace engineering.

    “Robin Midgett, VADL laboratory manager and rocketry mentor, has been a great ally — combining his enthusiasm for rocketry with the encyclopedic knowledge of the middle Tennessee landscape to make field engineering a delightful and safe experience for the students,” Anilkumar said.

    “We are convinced that all of these VADL alumni will go on to shine in the aerospace industry and continue to make Vanderbilt proud.”

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    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.
    Related links

     
  • richardmitnick 12:45 pm on January 17, 2017 Permalink | Reply
    Tags: , , , Vanderbilt U   

    From Vanderbilt: “Softening tumor tissue could aid cancer treatments” 

    Vanderbilt U Bloc

    Vanderbilt University

    Jan. 16, 2017
    Liz Entman

    Softening tumors’ blood vessels may help more chemo reach the cancer

    Normally, the glue that holds cells together in the human body – what scientists call the extracellular matrix – is soft and pliable. But when a metastatic tumor forms it causes the matrix surrounding it to stiffen.

    According to a new study, this mechanical effect produces changes in the blood vessels that feed the tumor in a way that can reduce the effectiveness of chemotherapeutics and radiation treatments. The finding suggests that softening this protective layer could make existing cancer treatments more effective.

    2
    Cynthia Reinhart-King (Steve Green/Vanderbilt)

    The study was published Dec. 22 in the Proceedings of the National Academy of Sciences, by a team of researchers led by Vanderbilt Professor of Biomedical Engineering Cynthia Reinhart-King, which includes postdoctoral researcher François Bordeleau in the Reinhart-King group along with collaborators from Cornell University. The report is titled Matrix Stiffening Promotes a Tumor Vasculature Phenotype.

    For years, the idea has been that the way to treat tumors was to starve them by killing off their blood vessels. While that works in some cases, in others it only serves to make the tumor more aggressive, Reinhart-King said, adding: “There are ways tumors can grow in the absence of those nutrients, and they get more aggressive. At the same time, they may also stop responding to some chemotherapeutics and radiation treatments.”

    A metastatic tumor’s blood vessels tend to be malformed and more permeable than blood vessels in healthy tissue. For this reason, fluid tends to leak from the vessels, building up pressure inside the tumor that prevents drugs from getting to their target.

    “Basically, as fluid leaks out of the blood vessels, it causes high pressures to build up in the tumor. These high pressures can cause blood flow to stall or even reverse and vessels tocollapse,” Reinhart-King said. “So fluid, including the drugs, cannot reach the tumor tissue.”

    3
    Image of a mammary tumor stained for cell nuclei (in blue), blood vessels (in green) and the protein beta-catenin that causes cells to stick together (in red) (Reinhart-King Lab / Vanderbilt)

    Unlike in previous work in this area, Reinhart-King and Bordeleau see the vascular breakdown as a product of the stiffening of the tumor and its matrix, which triggers proteins in cells to alter vascular growth and integrity. Previous work has targeted chemical factors, in particular vascular endothelial growth factor.

    “The idea that you would want to restore barrier integrity and help blood vessels is not a new one,” Reinhart-King said. “The idea that we discovered is that it’s controlled through matrix stiffness.” This, in turn, suggests that promoting healthy vasculature through a softening of the extracellular matrix would use the tumor itself as a conduit for delivering cancer-killing drugs.

    “What we show,” Reinhart-King said, “is that we can drive a lot of the same behaviors that are typically thought to occur due to chemical changes, by changing the mechanical properties of the tumor.”

    This work was supported by National Institutes of Health grants R01-HL127499 and R01-CA163255 and National Science Foundation awards 1055502 and 435755.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Vanderbilt Campus

     
  • richardmitnick 9:30 am on December 28, 2016 Permalink | Reply
    Tags: , , , Vanderbilt U   

    From Vanderbilt: “Investigational new drug for Alzheimer’s scheduled for first study in humans” 

    Vanderbilt U Bloc

    Vanderbilt University

    Dec. 27, 2016
    Bill Snyder

    Vanderbilt University scientists have received notification from the U.S. Food and Drug Administration (FDA) that testing in humans may proceed for an investigational new drug for Alzheimer’s disease after more than 10 years of research by scientists at Vanderbilt University and Vanderbilt University Medical Center.

    It is relatively uncharted territory for an academic drug discovery group to take a molecule from the laboratory setting to the clinical trials stage.

    “The movement to the clinical phase of the research is the result of tireless colleagues reaching across disciplines in pursuit of the shared goal of hoping to someday improve the lives of individuals with Alzheimer’s disease and possibly other brain disorders, such as schizophrenia,” said Provost and Vice Chancellor for Academic Affairs Susan R. Wente, Ph.D. “This work exactly illustrates the critical role that basic science conducted in partnership with a world-class medical center can play in advancing knowledge in an attempt to fight a devastating disease.”

    For Alzheimer’s disease, the aim is for the investigational drug to target major pathologies of the disease and selectively activate a key receptor in the brain. The Vanderbilt researchers believe that the current standard of care for Alzheimer’s disease, cholinesterase inhibitors, has a different mechanism of action. They are hoping to establish through future clinical testing that the molecule is broadly effective across a number of cognitive and neuropsychiatric disorders, including schizophrenia.

    1
    P. Jeffrey Conn, Ph.D.

    “This is the first instance I am aware of where an academic drug discovery group moved a molecule designed to hopefully treat a chronic brain disorder all the way from early discovery to human trials without there being, at some point along the way, a pharmaceutical partner,” said P. Jeffrey Conn, Ph.D., Lee E. Limbird Professor of Pharmacology in the Vanderbilt University School of Medicine and director of the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD).

    “And that really is crossing what people refer to all of the time as the ‘Valley of Death,’ where good research discoveries have a hard time moving into the clinical testing phase due to lack of funding,” he said. “Importantly, at this early stage, the FDA has only granted permission to assess potential safety of this investigational new drug in healthy volunteers” said Conn. “We cannot predict the outcome, but if these studies are successful in demonstrating that the investigational drug can be safely administered to humans, this would pave the way to allow filing of additional applications with the FDA to seek permission to advance to testing for efficacy in improving cognitive function in patients suffering from Alzheimer’s disease, and possibly schizophrenia or other brain disorders. While we cannot predict the outcome of any future safety or efficacy studies, this decision by FDA allowing clinical research to begin represents a major milestone in allowing us to hopefully provide answers to those critical questions in the future.”

    2
    Craig W. Lindsley, Ph.D.

    VCNDD Co-Director Craig W. Lindsley, Ph.D., director of Medicinal Chemistry and William K. Warren, Jr. Professor of Medicine, said Phase I testing will assess drug safety and tolerability in healthy volunteer participants, a process that could take a year. If successful, the Phase II and III studies would include efficacy assessments in patients with Alzheimer’s disease and could take three to five years to complete.

    “We are hoping to address what we see as an unmet medical need,” Lindsley said. “For Alzheimer’s patients, the standard of care for symptomatic treatment remains cholinesterase inhibitors, which are 25 years old at this point. There hasn’t been any real scientific advancement in this field in a long time.”

    Lindsley and Conn credit The William K. Warren Foundation for its philanthropic investments along the way to make clinical trials for this investigational drug a reality.

    “One of the most challenging things about doing this in an academic environment is funding,” Lindsley said. “Every step requires funding and if there is a delay or break in funding, then everything sits idle and potentially innovative approaches for patient care do not advance.”

    “Being matched with the Warrens happened serendipitously. They have invested so much in our programs, and it is wonderful to show them progress on their investments,” he said. “Without the financial support from the Warrens, this investigational drug would not be poised to enter human clinical trials.”

    The William K. Warren Foundation Chief Executive Officer John-Kelly Warren said he is gratified that FDA has allowed for the investigational drug to proceed to testing in human beings.

    “Although this is an important sequential milestone, the only milestone that matters to us is the hope that one day we will learn that this investigational new drug has positively and safely changed the life of a patient suffering from a brain disorder such as schizophrenia or Alzheimer’s disease,” Warren said.

    “That day will warrant a celebration felt in the heavens. Until then, we are prepared to support the VCNDD research team until they can deliver the necessary results,” he said.

    A NIH National Cooperative Drug Discovery/Development grant funded the early basic science and discovery of this investigational drug and the Alzheimer’s Drug Discovery Foundation and Harrington Discovery Institute helped support some of the key toxicity studies that FDA required, Conn said.

    “The investigational new drug has the potential to improve cognitive functions with fewer unwanted side effects. This could someday be an important advance for the treatment of cognitive deficits in psychiatric disorders and Alzheimer’s disease,” said Joshua Gordon, M.D., Ph.D., director of the National Institute of Mental Health, which co-funded the research.

    Conn and Lindsley said Vanderbilt’s “team science” approach included contributions from the director of Translational Pharmacology and Development for the VCNDD and Assistant Professor Carrie K. Jones, Ph.D., who coordinated the IND drafting, submission, and subsequent development into Phase I, director of Molecular Pharmacology for the VCNDD and Research Associate Professor of Pharmacology Colleen Niswender, Ph.D., for the molecular pharmacology; Research Assistant Professor of Pharmacology Jerri Rook, Ph.D., for the behavioral studies; and Research Assistant Professor of Pharmacology Thomas Bridges, Ph.D., and Research Assistant Professor of Pharmacology Anna Blobaum, Ph.D., for drug metabolism and pharmacokinetic profiling.

    Paul Newhouse, M.D., director of the Center for Cognitive Medicine at VUMC and Jim Turner Professor in Cognitive Disorders, is expected to lead the upcoming clinical study funded in part by the Alzheimer’s Association and Alzheimer’s Drug Discovery Foundation.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Vanderbilt Campus

     
  • richardmitnick 5:52 am on September 10, 2016 Permalink | Reply
    Tags: , , , Vanderbilt U   

    From Vanderbilt: “In search of new cancer targets” 

    Vanderbilt U Bloc

    Vanderbilt University

    Sep. 9, 2016
    Leigh MacMillan

    Molecularly heterogeneous cancers such as triple-negative breast cancer are challenging to treat, because they often lack the “driver” mutations that are targeted by the newest cancer therapies. These cancers exhibit genomic instability, resulting in chromosomal rearrangements and gene fusions, and identifying these alterations is technically difficult.

    Timothy Shaver and Brian Lehmann, Ph.D., working with Jennifer Pietenpol, Ph.D., developed a new algorithm, Segmental Transcript Analysis (STA), to predict gene rearrangements.

    Using STA, they identified multiple known and novel gene rearrangements in triple-negative breast cancer and then expanded their analysis to other malignancies using a cohort from The Cancer Genome Atlas.

    Two of the gene rearrangements that the team characterized in triple-negative breast cancer involve molecular targets for therapies already in clinical investigation or development.

    The findings, reported Aug. 15 in Cancer Research, provide evidence that STA is an effective prediction tool for gene rearrangements and highlight the need to advance gene fusion detection for molecularly heterogeneous cancers.

    This research was supported by grants from the National Institutes of Health (CA183531, GM008554, CA098131, CA105436, CA068485) and from the Susan G. Komen Foundation.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Vanderbilt Campus

     
  • richardmitnick 9:57 am on September 9, 2016 Permalink | Reply
    Tags: , , , , , Vanderbilt U,   

    From Vanderbilt: “Investigators create ‘Trojan Horse’ to fight Ebola” 

    Vanderbilt U Bloc

    Vanderbilt University

    Sep. 8, 2016
    Bill Snyder
    william.snyder@Vanderbilt.Edu
    (615) 322-4747

    A multi-center research team including scientists from the Vanderbilt Vaccine Center has come up with a clever “Trojan Horse” strategy for thwarting the highly lethal Ebola virus.

    Using “bispecific” antibodies — two monoclonal antibodies combined into a single package — they first tricked the virus into revealing a normally hidden binding site required for infection. Then in a mouse model, they blocked the site, fully protecting the animals from Ebola infection.

    Their findings, reported in this week’s Science magazine, suggest that this two-step, “deliver-and-block” strategy can provide broad protection against Ebola and other members of its hemorrhagic filovirus family, including the Marburg virus.

    We were intrigued to find this remarkable antibody that has the capacity to inhibit both Marburg and Ebola viruses,” said James Crowe Jr., M.D., Ann Scott Carell Professor in the Vanderbilt University School of Medicine and director of the Vanderbilt Vaccine Center at Vanderbilt University Medical Center.

    “The team’s feat of delivering the antibody into cells using creative engineering tricks so that it can kill Ebola inside cells is very exciting,” Crowe said.

    This advance is only the latest in a string of fundamental discoveries made during the past decade by a far-flung group of researchers including Crowe and four other corresponding authors of the paper.

    The four are Kartik Chandran, Ph.D., and Jonathan Lai, Ph.D., of Albert Einstein College of Medicine in New York, John Dye, Ph.D., of the U.S. Army Medical Research Institute of Infectious Diseases in Fort Detrick, Maryland, and Javad Aman, Ph.D., of Integrated Biotherapeutics in Gaithersburg, Maryland.

    Like other viruses, Ebola must “hijack” factors in the cells it infects to make copies of itself. As a first step, the virus enters a vesicle called an endosome inside the cell. There it commandeers two cellular enzymes called proteases to cut a sugar-bearing glycoprotein on its surface in two.

    Cleavage of the glycoprotein reveals a previously hidden receptor-binding site that attaches to another cellular factor, a cholesterol transporter protein called Niemann–Pick C1 or NPC1. This step is essential for infection to occur.

    Mutations in the NPC1 gene result in an abnormal protein that causes the rare lipid storage disorder Niemann-Pick type C disease. While patients with this disease are often quite ill, their abnormal NPC1 protein also renders them resistant to infection by Ebola and the related Marburg virus.

    Last year, Crowe, Vanderbilt graduate student Andrew Flyak and colleagues at The Scripps Research Institute in La Jolla, California, reported that a human survivor of a severe Marburg infection had neutralizing antibodies that recognized and blocked the NPC1 binding site in Marburg virus

    These antibodies also could bind to the Ebola virus, but only to the form of the virus inside cells.

    Crowe and Flyak followed up that finding by generating a “monoclonal” antibody, called MR72, which specifically recognized and could block the NPC1 binding site. To actually prevent Ebola virus infection, however, they’d have to get the antibody into the endosome inside the cell where the action is taking place.

    To do that, the researchers fused MR72 to another antibody, called FVM09, which recognizes and attaches to the Ebola glycoprotein before it is cut in two. The result was an immunological “Trojan horse.” Once the virus brought its antibody cargo into the endosome, MR72 went to work, and blocked infection.

    “This Trojan horse bispecific antibody approach may also find utility against other viral pathogens known to use intracellular receptors,” they concluded.

    Other contributors to the current study were Erica Ollmann Saphire, Ph.D., at Scripps and Zachary Bornholdt, Ph.D., now at Mapp Pharmaceutical in San Diego. The study was supported in part by National Institutes of Health grants AI109762, AI088027 and AI122403.

    See the full article here .

    You can Help Stamp Out EBOLA.

    This WCG project runs at Scripps Institute

    Outsmart Ebola Together

    Visit World Community Grid (WCG). Download and install the BOINC software on which it runs. Attach to the Outsmart Ebola Together project. This will allow WCG to use your computer’s free CPU cycles to process computational data for the project.

    WCGLarge
    WCG Logo New

    BOINCLarge
    BOINC WallPaper

    While you are at WCG and BOINC, check out the other very worthwhile projects running on this software. All project results are “open source”, free for the use of scientists world while to advance health and other issues of mankind.

    MyBOINC

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Vanderbilt Campus

     
  • richardmitnick 8:33 am on September 9, 2016 Permalink | Reply
    Tags: , , Myocardial infarction, Vanderbilt U   

    From Vanderbilt: “Going after the heart attack Gremlin” 

    Vanderbilt U Bloc

    Vanderbilt University

    Sep. 8, 2016
    Sanjay Mishra

    Myocardial infarction (MI) or heart attack is the major cause of death in men and women in the United States. Because it interrupts the heart’s oxygen supply, MI causes irreversible tissue damage that can lead to heart failure.

    1
    Blausen Medical Communications, Inc.
    A protein called Gremlin 2 (Grem2), which is required for early cardiac development, also is strongly induced in the heart after experimental MI. However, little is known about the function of Grem2 after cardiac injury.

    Now, in a paper published recently in the journal Circulation Research, Antonis Hatzopoulos, Ph.D., and colleagues show that Grem2 provides a molecular barrier that controls the magnitude and extent of inflammation after MI.

    They show that Grem2 suppresses the signaling of bone morphogenetic protein (BMP). BMP signaling plays an important role in heart development but its activation following ischemic injury regulates the inflammatory response.

    Their findings suggest a new strategy to limit the adverse effects of excessive inflammation following MI.

    This research was supported by grants from the National Institutes of Health (HL083958, HL100398, GM114640) and by institutional support from Vanderbilt University Medical Center.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Vanderbilt Campus

     
  • richardmitnick 8:05 am on September 1, 2016 Permalink | Reply
    Tags: , , , Neuroblastoma, Vanderbilt U   

    From Vanderbilt: “Proliferative capacity of neuroblastoma” 

    Vanderbilt U Bloc

    Vanderbilt University

    Aug. 31, 2016
    Sanjay Mishra

    Neuroblastoma is a neural crest cell-derived extracranial solid cancer that affects infants and young children. The most vigorous of these cancers spreads through self-renewing cancer stem cells. Knowing the nature of these cells is essential to understanding the progression of neuroblastoma and devising the right treatment strategy.

    Reporting in the journal Biochemical and Biophysical Research Communications, Dai Chung, M.D., and colleagues use a technique called “limiting dilution analysis” to show that the frequency with which neuroblastoma stem cells form spheres in suspension cultures accurately quantifies their stemness, or ability to “self-renew.”

    Cell lines formed spheres more frequently when the MYCN oncogene was overactive. Retinoic acid, used clinically to induce differentiation of residual disease after chemotherapy and radiation, almost blocked sphere formation entirely, while fibroblast growth factor (FGF) promoted sphere formation.

    Limiting dilution analysis is an accurate method of quantifying sphere-forming frequency, and should be adopted as an effective way to assess the stemness or proliferative capacity of neuroblastoma stem cells, they conclude.

    This research was supported by a grant from the National Institutes of Health (DK061470) and by a Rally Foundation for Cancer Research Pediatric Oncology Fellowship Award.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Vanderbilt Campus

     
  • richardmitnick 4:18 pm on May 6, 2016 Permalink | Reply
    Tags: , , Vanderbilt U   

    From Vanderbilt: “Current cancer drug discovery method flawed: VUMC study” 

    Vanderbilt U Bloc

    Vanderbilt University

    May 5, 2016
    Leigh MacMillan

    The primary method used to test compounds for anti-cancer activity in cells is flawed, Vanderbilt University researchers reported* May 2 in Nature Methods. The findings cast doubt on methods used by the entire scientific enterprise and pharmaceutical industry to discover new cancer drugs.

    “More than 90 percent of candidate cancer drugs fail in late-stage clinical trials, costing hundreds of millions of dollars,” said Vito Quaranta, M.D., director of the Quantitative Systems Biology Center at Vanderbilt. “The flawed in vitro drug discovery metric may not be the only responsible factor, but it may be worth pursuing an estimate of its impact.”

    Quaranta and his colleagues have developed a new metric to evaluate a compound’s effect on cell proliferation — called the DIP (drug-induced proliferation) rate — that overcomes the flawed bias in the traditional method.

    For more than 30 years, scientists have evaluated the ability of a compound to kill cells by adding the compound to cells and counting how many cells are alive after 72 hours. But these “proliferation assays” that measure cell number at a single time point don’t take into account the bias introduced by exponential cell proliferation, even in the presence of the drug, said Darren Tyson, Ph.D., co-author and research assistant professor of Cancer Biology.

    “Cells are not uniform; they all proliferate exponentially, but at different rates,” said Quaranta, professor of Cancer Biology. “At 72 hours, some cells will have doubled three times and others will not have doubled at all.”

    In addition, he noted, drugs don’t all behave the same way on every cell line — for example, a drug might have an immediate effect on one cell line and a delayed effect on another.

    In a close collaboration with computational biologist Carlos Lopez, Ph.D., assistant professor of Cancer Biology, Quaranta’s team used a systems biology approach — a mixture of experimentation and mathematical modeling — to demonstrate the time-dependent bias in static proliferation assays and to develop the time-independent DIP rate metric.

    “Systems biology is what really makes the difference here,” Lopez said. “It’s about understanding cells — and life — as dynamic systems.”

    Tyson, an experimentalist, conceived the method with Leonard Harris, Ph.D., a systems biology postdoctoral fellow and co-first author Peter Frick, Ph.D., a recent Vanderbilt graduate.

    The findings have particular importance in light of recent international efforts to generate data sets that include the responses of “thousands of cell lines to hundreds of compounds,” Quaranta said. The Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases include drug response data along with genomic and proteomic data that detail each cell line’s molecular makeup.

    “The idea is to look for statistical correlations — these particular cell lines with this particular makeup are sensitive to these types of compounds — to use these large databases as discovery tools for new therapeutic targets in cancer,” Quaranta said. “If the metric by which you’ve evaluated the drug sensitivity of the cells is wrong, your statistical correlations are basically no good.”

    The researchers evaluated the responses of four different melanoma cell lines to the drug vemurafenib, currently used to treat melanoma, with the standard metric – used for the CCLE and GDSC databases — and with the DIP rate. In one cell line, they found a stark disagreement between the two metrics.

    “The static metric says that the cell line is very sensitive to vemurafenib. However, our analysis shows this is not the case,” Harris said. “A brief period of drug sensitivity, quickly followed by rebound, fools the static metric, but not the DIP rate.”

    The findings “suggest we should expect melanoma tumors treated with this drug to come back, and that’s what has happened, puzzling investigators,” Quaranta added. “DIP rate analyses may help solve this conundrum, leading to better treatment strategies.”

    The DIP rate metric offers another advantage — it can reveal which drugs are truly cytotoxic (cell-killing), rather than merely cytostatic (cell growth-inhibiting). Although cytostatic drugs may initially have promising therapeutic effects, they may leave tumor cells alive that then have the potential to cause the cancer to recur.

    Quaranta noted that using the DIP rate is possible because of advances in automation, robotics, microscopy and image processing.

    His team has developed a software package that will be available to other researchers through a hyperlink in the Nature Methods paper. Quaranta is working with the Vanderbilt Center for Technology Transfer and Commercialization to identify commercial entities that can further refine the software and make it widely available to the research community to inform drug discovery.

    Other contributors to the research included Shawn Garbett in Biostatistics, and Keisha Hardeman and Bishal Paudel, graduate students in the Quaranta laboratory. This research was supported by grants from Uniting Against Lung Cancer, the Vanderbilt Breast Cancer SPORE, the National Institutes of Health (CA113007, CA174706, TR000445), and by a National Library of Medicine Fellowship.

    *Science paper:
    An unbiased metric of antiproliferative drug effect in vitro

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Vanderbilt Campus

     
c
Compose new post
j
Next post/Next comment
k
Previous post/Previous comment
r
Reply
e
Edit
o
Show/Hide comments
t
Go to top
l
Go to login
h
Show/Hide help
shift + esc
Cancel
%d bloggers like this: