OHSU research yields insight into aspirin’s anti-cancer effect

Acetylsalicylic acid, a.k.a. aspirin.

Acetylsalicylic acid, a.k.a. aspirin.

The anti-inflammatory and anti-platelet properties of aspirin have made it the subject of intensive investigation for over a century. More recently, aspirin use has been correlated with reduced long-term risk of some cancers, particularly colorectal cancer. The reasons remain unknown, as does the degree to which the effect comes from direct inhibition of cancer cells and how much is due to inhibition of platelet activation and function.

A study recently completed by a team of OHSU researchers and published in the American Journal of Physiology—Cell Physiology suggests the benefit of aspirin may be due to its effect on platelets rather than acting directly on tumor cells.

In a series of experiments with cultured cells, a team led by Owen McCarty, Ph.D., chair of the Department of Biomedical Engineering in the School of Medicine, showed that inhibition of platelets with low doses of aspirin cuts the signaling link between platelets and some cancer cells, which in turn knocks back cancer growth.

It is not yet known whether the cascade of effects observed in cell cultures works the same way in people. The new findings are not sufficient to justify taking aspirin solely to help prevent cancer. Aspirin has an effect mediated by platelets that may work in concert with aspirin’s anti-inflammatory properties to oppose malignant cell growth, and low doses of aspirin might eventually prove a safe and effective way to prevent cancer in patients at risk.

The research was supported by grants from the Altarum Institute, the National Institutes of Health, and the American Heart Association.

Read the OHSU release.

Supplemental funding available for research on sex/gender influences

The recently implemented NIH policy requiring grant applicants to consider sex as a biological variable in the design of basic and pre-clinical animal studies has prompted considerable discussion. Translating this policy into action is complex. For example, the cost associated with expanding the scope of a study to include additional cell lines or study animals is a pressing issue for many investigators.

The Office of Research on Women’s Health is responding to this concern by providing administrative supplements to support research highlighting the impact of sex/gender influences and/or sex and gender factors in basic, preclinical, clinical and behavioral studies. Supplemental applications, within the scope of the parent application, may include the following approaches:

  • Adding the opposite sex: Adding animal or human subjects, tissues or cells of the sex opposite to those used in the parent grant to allow sex/gender-based comparisons.
  • Increasing sample size: Adding more animal or human subjects, tissues or cells to a sample  to increase the power of a study for analysis of  sex/gender differences.
  • Conducting new experiments or comparative analyses: Developing new experimental approaches or comparative analyses of existing samples or datasets to investigate the role of sex/gender.

Supplemental applications must address at least one objective from Goals 1-3 of the NIH Strategic Plan for Women’s Health Research:

  1. Increase sex differences research in basic science studies.
  2. Incorporate findings of sex/gender in the design and development of new technologies, medical devices, and therapeutic drugs.
  3. Actualize personalized prevention, diagnostics, and therapeutics for girls and women.

The objectives of Goals 2 and 3 are of higher programmatic importance and applications studying one or more of these goals will be given higher consideration. For applications that address Goal 1, of special interest are studies to understand the influence of biological sex on cells, primary cell cultures, immortalized cell lines, transformed cells, and tissue explants.

The Office of Research on Women’s Health intends to commit $3,000,000 in FY 2017 to fund 30 awards. Supplemental application budgets are limited to $65,000 in direct costs but additional indirect costs may also be requested. The award project period is limited to one year. The parent grant must have at least 18 months of active support remaining from the supplement application due date, which is February 13, 2017. Guidelines on submitting your application can be found here. Still have questions? Contact your Grants and Contracts Administrator.

 

David Huang, M.D., Ph.D., receives National Academy of Inventors award

OHSU Casey Eye Institute researcher David Huang, M.D., Ph.D., has been named a Fellow of the National Academy of Inventors. Academic inventors and innovators elected to the rank of NAI Fellow were nominated by their peers for outstanding contributions to innovation in areas such as patents and licensing, innovative discovery and technology, significant impact on society, and support and enhancement of innovation.huang120px

Huang, the Peterson Professor of Ophthalmology and Professor of Biomedical Engineering at OHSU, has indeed demonstrated a prolific spirit of innovation in the field of vision research. Huang is a co-inventor of optical coherence tomography (OCT), an imaging technology that has been applied to the measurement of eye structures with unprecedented precision. More recently he has pioneered anterior segment OCT and OCT angiography. He has 16 issued patents and 14 pending patents in the areas of OCT, mobile health testing, tissue engineering and corneal laser surgery. He has published more than 180 peer-reviewed articles – his seminal article on OCT, published in Science in 1991, has been cited more than 10,000 times – and edited 7 books.

Other awards Huang has received include the Champalimaud Vision Award, the ARVO Jonas Friedenwald Award, and the Senior Achievement Award from the American Academy of Ophthalmology. Dr. Huang leads the Center for Ophthalmic Optics and Lasers (www.COOLLab.net). He is a founder of Gobiquity Mobile Health, Inc. (www.gobiquity.com), a maker of mobile diagnostic apps and devices for medical professionals.

The 2016 NAI Fellows were evaluated by a selection committee that included 19 members, comprising NAI Fellows, recipients of U.S. National Medals, National Inventors Hall of Fame inductees, members of the National Academies and senior officials from the USPTO, National Institute of Standards and Technology, Association of American Universities, American Association for the Advancement of Science, Association of Public and Land-grant Universities, Association of University Technology Managers, and other prominent organizations. The 2016 Fellows will be inducted on April 6, 2017, as part of the Sixth Annual Conference of the National Academy of Inventors at the John F. Kennedy Presidential Library & Museum in Boston.

 

 

OHSU’s Erick Turner to present at next Data Jamboree, Dec. 16

Join the OHSU Library and Computational Biology Program for December’s Data Jamboree. This month’s event will focus on the role of open content and data in advancing biomedical research and human health. Erick Turner, M.D., Associate Professor at OHSU and Staff Psychiatrist at the Portland VA Medical Center, will introduce OpenTrialsFDA, a current finalist for the highly competitive Open Science Prize.

OpenTrialsFDA is a platform developed by Turner and associates that aims to increase access to and the utility of FDA drug approval packages that often contain information on clinical trials that have never been published.  When these data are integrated into a systematic review or meta-analysis, it can sometimes dramatically shift a drug’s risk-benefit ratio. Although the FDA makes the reviews available via its web portal Drugs@FDA, the documents are notoriously difficult to search and aggregate. As a consequence, they are rarely used by clinicians and researchers, despite their immense value. OpenTrialsFDA intends to change this by allowing researchers, clinicians, the public, developers, and third party platforms to access, search, and build upon this data.

Friday, Dec. 16
2:30 – 5:00 PM (hackathon will continue past 5:00)
Collaborative Life Sciences Building (CLSB), 3A003
Food & Drink provided

Turner’s keynote talk will be followed by an overview of the NIH’s new clinical trial data sharing requirements and two concurrent hands-on sessions:

  • Searching the OpenTrialsFDA website, understanding the contents of an FDA drug approval package, and how the data can benefit different use cases, such as meta-analysis and systematic reviews.
  • An OpenTrialsFDA hackathon using the OpenTrials API.  Attendees will have the opportunity to use their research, development, clinical, and visualization expertise (to name a few) to explore, present, and build upon the OpenTrials data and the OpenTrialsFDA application. Please note, no technical expertise is required, as there will be multiple ways of contributing.

All are welcome to attend, including OHSU faculty, students, and staff as well as Portland area science enthusiasts and developers!

Community Partnership Program funds 10 new cancer research projects across the state

OHSU researchers brought in $389 million in extramural funding in fiscal year 2016. But OHSU also funds projects across Oregon through mechanisms like the Knight Cancer Institute’s  Community Partnership Program.

The OHSU Knight Cancer Institute has announced grant funding for ten projects around the state that target communities’ cancer-related needs — from prevention through survivorship. These grants provide funding and resources to help develop programs and guide projects toward evidence-based practices and evaluation measures. The program also offers opportunities for networking and collaborating with OHSU faculty.

To date, Community Partnership Program grants have funded 52 projects in 33 of Oregon’s 36 counties, with 89 percent of projects targeting rural communities. The program has funded a variety of projects, including expanding cancer screenings, prevention through healthy behaviors, and survivorship support.

Read the OHSU release.

Carsten Schultz and lab develop new imaging platform for profiling cell signaling networks

Carsten Schultz, Ph.D., chair of the OHSU School of Medicine Department of Physiology and Pharmacology

Carsten Schultz, Ph.D., chair of the OHSU School of Medicine Department of Physiology and Pharmacology

Cellular development, tissue repair, immunity, and normal homeostasis rely on cells perceiving and appropriately responding to their microenvironment. While significant knowledge exists on the individual aspects of these cell signaling pathways, the question persists on how cell signaling networks integrate and process information from multiple extracellular cues. Understanding these processes may help develop therapies to more effectively treat diseases such as cancer and diabetes that result from errors in processing information.

A study published December 8 by Carsten Schultz, Ph.D., chair of the OHSU School of Medicine’s Department of Physiology and Pharmacology, in Cell Chemical Biology reports development of a new imaging platform for monitoring cell signaling network activity that may, when combined with gene expression studies, answer long-standing questions about how this complex communication system works.

Dr. Schultz and his team developed a method that allows comprehensive system-level analysis of multiple signaling pathway dynamics under identical conditions. Such a method supports research into how cellular signaling networks integrate information from the extracellular environment, how they evoke specific cellular responses, and, most importantly, how normal signaling is rewired over the course of a disease.

The team combined cell microarray technology with Förster resonance energy transfer (FRET) biosensors and live-cell imaging. The study demonstrated that the platform enabled multi-dimensional data generation in a single experiment and successfully demonstrated the effect of perturbing the network by drugs. They also found that crosstalk of two growth factors produces distinct activity patterns.

The platform may in the future be applied to develop comprehensive models of signaling networks and help investigate the mechanisms of action, as well as side effects of therapeutic treatments. The findings may provide information relevant to disease progression and prognosis, design of therapeutic treatment, and drug discovery.

The research team included Dmitry Kuchenov, Vibor Laketa, and Frank Stein from the European Molecular Biology Laboratory (EMBL) Cell Biology and Biophysics Unit in Heidelberg, Germany, and Florian Salopiata and Ursula Klingmüller of the Translational Lung Research Center Heidelberg, a German Center for Lung Research site. Schultz joined OHSU in the fall of 2016 as chair of the Department of Physiology and Pharmacology.

The work was supported by the Schultz team at the European Molecular Biology Laboratory, the German Federal Ministry of Education and Research, the DFG (SFB 1129), and the Joachim Herz Foundation. The Klingmüller group was supported by the German Federal Ministry of Education and Research through the LungSysII consortium, and the German Center for Lung Research.

OHSU’s Erick Turner and team finalists for Open Science Prize: voting open through Jan. 6

Alongside the growing availability of high-value open data for research are key obstacles — discoverability and the ability to access and use that data. The global science competition Open Science Prize was launched by the Wellcome Trust, US National Institutes of Health, and the Howard Hughes Medical Institute to encourage new ways to remove these obstacles. In the first phase of this new initiative, six international teams received prizes to develop prototypes. The teams presented their prototypes at the BD2K Open Data Science Symposium in Washington, D.C., on December 1.

A bigger picture

Contrasting the journal version of antidepressant trials with FDA information.

OpenTrialsFDA, one of the finalist prototypes, was presented by Erick Turner, MD, associate professor in the OHSU Psychiatry Department and staff psychiatrist at the Portland VAMC, along with collaborators Dr. Ben Goldacre, senior clinical research fellow in the Centre for Evidence Based Medicine at the University of Oxford, and Open Knowledge International.

The prototype is a new application of existing open data techniques and code designed to improve access to drug approval packages submitted to and made available by the Food and Drug Administration. These documents contain detailed information about the methods and results of clinical trials and often contain unpublished information on clinical trials.

The FDA databases are notoriously difficult to access, search, and aggregate. Much of the information in these packages is only available in image form and is not searchable. The OpenTrialsFDA application converts documents into searchable text, scrapes all the relevant data and documents from the FDA documents, runs Optical Character Recognition across all documents, links this information to other clinical trial data, and presents it through a user-friendly web interface.

The OpenTrialsFDA prototype definitely fits the Open Science Prize goal: to make the outputs from science and the research process more broadly accessible.

Voting is open from now until 6 January 2017. The public is invited to help select the most promising and innovative prototype from the six finalists. One prototype will receive the grand prize of $230,000.

Funding opportunity for women’s health research

The OHSU Center for Women’s Health Circle of Giving is now accepting submissions for its 2017 Women’s Health Research Funding Opportunity. Prior to submitting an application, a letter of intent is first required. The letter of intent is due Jan. 6, 2017, and the application is due Jan. 22, 2017. Circle of Giving funding is intended to support new or established investigators interested in developing innovative directions in women’s health research.

Applications will be accepted from faculty at the rank of lecturer, assistant, associate, or full professor. Applications may be in basic science, clinical investigation, population health, or behavioral research. The pilot project conducted using these seed funds is expected to lead to additional research funded by federal and non-federal sources. The proposed research must be intended to produce a tangible improvement in women’s health.

The Circle expects to award $125,000 to support one project for one year. There may be opportunity for a second award this year.

Please view the full RFP for additional information. Applications must be submitted via OHSU’s Competitive Application Portal (CAP).

New OHSU research suggests possible target in fight against Alzheimer’s

Two images compare brain scans from an older individual who had Alzheimer's (left) with an older cognitively healthy individual (right).

Two images compare brain scans from an older individual who had Alzheimer’s (left) with an older cognitively healthy individual (right).

In most of the human body, the lymphatic system clears away waste and toxins. The brain, however, has no lymphatic vessels. Its waste, including plaques associated with Alzheimer’s disease, is cleaned instead by cerebrospinal fluid recirculating through brain tissue. Over the course of five years, research in the lab of Jeffrey Iliff, Ph.D., has defined this brain-wide paravascular pathway, called the glymphatic system.

Iliff’s team has found that this recirculation is modulated by sleep and also that, as the brain ages, this waste-clearing process is impaired. Their work continues to investigate what causes the glymphatic system to slow. In research findings published November 28 in the journal JAMA Neurology, Iliff demonstrates the possible role of aquaporin-4, a membrane protein in the brain and key component of the glymphatic system.

The study examined 79 brains donated through the Oregon Brain Bank, a part of the OHSU Layton Aging and Alzheimer’s Disease Center. Researchers found that in the brains of younger people and older people without Alzheimer’s, the aquaporin-4 protein was well organized, lining the blood vessels of the brain. However, within the brains of people with Alzheimer’s, the aquaporin-4 protein appeared disorganized, which may reflect an inability of these brains to efficiently clear away wastes like amyloid beta.

The study suggests that future research focusing on aquaporin-4 might find it to be a useful target for potentially preventing and treating Alzheimer’s disease.

In addition to Iliff, co-authors included Douglas M. Zeppenfeld; Matthew Simon, J. Douglas Haswell, and Daryl D’Abreo of the OHSU Department of Anesthesiology and Perioperative Medicine. See the paper for a full list of authors.

This work was supported by funding from the American Heart Association, grant 12SDG11820014, the Oregon Partnership for Alzheimer’s Research, grants from the Research and Development Office of the Department of Veterans Affairs and the National Institutes of Health (NS089709), including Alzheimer’s Disease Center grant AG08017 from the National Institute on Aging that supported the longitudinal follow-up and subsequent brain autopsies providing the human brain samples used in this study.

Read the full OHSU news release.

Oregon Hearing Research Center scientists featured on front page of the Oregonian

The Oregonian featured OHSU’s Oregon Hearing Research Center on page 1 of its Nov. 25 print version and on its website, highlighting the Center’s four scientists with hearing loss. Peter Steyger, Ph.D., Lina Reiss, Ph.D., John Brigande, Ph.D., and Alfred Nuttall, Ph.D., belong to OHSU’s team of researchers investigating causes and solutions to hearing loss. Their research ranges from toxicity of certain pharmaceutical drugs to genetic therapies to prevent deafness through treatments in utero. Also featured is Frederick Gallun, a Graduate Studies faculty member. Read the article “OHSU’s deaf scientists lead charge in hearing research on some of the innovative auditory science conducted at OHSU. 

 

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