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. 

 

NIH seeks input on data sharing and data management

rfi-imageNIH is seeking stakeholder feedback on strategies for data management, sharing, and citation as part of an ongoing effort to ensure the results of federally-funded scientific research are made available to the public. Specifically, NIH wants to hear from data users, data generators, and data scientists on issues pertaining to what types of data should be shared; the costs and benefits of sharing different types of data; and standards for citation of data and software. Your feedback will help shape priorities and be considered in developing new NIH policies in this area.

Comments will be accepted until Thursday, Dec. 29 and can be submitted here.

Friends of Doernbecher research grant applications due Feb. 10

Friends-of-DoernbecherFriends of Doernbecher, a volunteer organization that raises funds for Doernbecher Children’s Hospital at OHSU, seeks proposals for pediatric-related research projects and programs. The grant program, which provides up to $175,000, is open to any employee of OHSU or Doernbecher proposing research related to children’s health. This includes (but is not limited to) OHSU and Doernbecher faculty, clinical and research staff, graduate students, medical students, fellows, and postdoctoral fellows. Grant applications are due February 10, 2017.

View program guidelines and application instructions here.

For questions, contact Cassady Kennebeck at at 503-220-8344 or kennebec@ohsu.edu.

New OHSU research provides key insight about mitochondrial replacement therapy

Dr. Shoukhrat Mitalipov

Dr. Shoukhrat Mitalipov

No treatments exist for children born with mitochondrial diseases, but a series of discoveries in the OHSU Center for Embryonic Cell and Gene Therapy is making progress on a technique that prevents transmission of these often-fatal genetic diseases, which are passed on from mothers to their children. The latest findings were published on Nov. 30 in the journal Nature.

OHSU scientist Shoukhrat Mitalipov, Ph.D., led a team that successfully prevented transmission of genetic defects in mitochondrial DNA in the cells of monkeys in 2009 and in human cells in 2012.

In the procedure, mitochondrial replacement therapy, the mother’s nucleus is transferred into a donor’s egg that has had its nucleus removed. The resulting egg includes the donor’s healthy mitochondria and the mother’s nucleus. This nuclear DNA determines functions ranging from organ structure and appearance to personality and intellectual characteristics.

A persistent risk with the procedure is transferring small amounts of defective mitochondria from the mother’s DNA to the donor cell, which can result in a gradual return to the mutated mitochondria and mitochondrial disease.

The findings published today suggest a way to reduce this risk — selecting egg donors whose mitochondrial DNA is compatible with the mother’s ancestral mitochondria. Similar groups of mitochondrial DNA are known as haplotypes, each of which represents major branching points on the human genetic family tree.  The team proposes setting donor mitochondrial DNA matching criteria to avoid a return of mutant mitochondria.

Mitochondrial mutations cause a range of diseases, many of which affect organs with high-energy demands such as the heart, muscle and brain. Currently, the U.S. government forbids clinical trials of mitochondrial replacement therapy. Britain has authorized such studies.  The first baby treated with mitochondrial replacement therapy was born in Mexico earlier this year.

OHSU researchers who contributed to the study also include Eunju Kang, Nuria Marti Gutierrez, and Amy Koski, members of the Center for Embryonic Cell and Gene Therapy. See the complete list of authors.

Funders of the studies include the Leducq Foundation, OHSU institutional funds and Cincinnati Children’s Hospital Research Foundation.

Read the full OHSU news release.

Funding Focus: Promoting your science, Dec. 19

In the modern information economy, it can be hard to get attention for your science—whether it’s from traditional media, social media, or even with tools like Research Gate. Join this panel discussion to learn about best practices for promoting your science and the OHSU resources that can help you. Find out how to work with OHSU’s media relations and social media departments—and what you can do to promote your research yourself.

Panelists include Tamara Hargens-Bradley, associate director, OHSU Media Relations; Kathryn Peck, social media manager, OHSU Brand Strategy; and Robin Champieux, scholarly communications librarian.

Monday, Dec. 19
noon to 1 p.m.
Vollum Institute M1441

This discussion will be followed up with an intensive workshop during OHSU Research Week, May 1-3.

Funding Focus is a series of workshops that Research Funding and Development Services offers throughout the year to share advice, tips, and general information on funding for the OHSU research community. Faculty, postdoctoral fellows, graduate students, and administrators are all welcome to attend. No registration is required.

Questions? Write funding@ohsu.edu.

Presidential bridge funding applications due Jan. 5

The Office of the Senior Vice President for Research has released its call for proposals for the FY17 winter OHSU Presidential Bridge Funding Program. Bridge funding is available for established investigators threatened by an imminent lapse in research support. Investigators can request up to $50,000 in funding for one year to help bridge them while they generate data to restore funding. Up to 3 awards will be made this funding cycle.

Awards are available only to OHSU investigators. The PI must be an independent scientist. Independence is defined by rank at the level of assistant professor or above; committed institutional support such as space and salary; a track record of first-authored or senior-authored publications; a recent history of federal (or similar) funding; and imminently planned or pending application for funding on a national level. Postdoctoral fellows and similar trainees are not eligible to apply.

Applications must include the following:

  • Bridge Funding Request describing the need for bridge funding, efforts that have already been made to secure funding and how bridge funds will be used to increase the likelihood of funding renewal
  • Letter of support from department chair or unit head documenting, among other things, any institutional commitment to the PI during the bridging period and beyond
  • Reviewer comments and priority scores
  • CV or biosketch
  • Budget

Applications are due by 5 p.m. on Thursday, January 5, 2017 and must be submitted online via OHSU’s Competitive Application Portal (CAP). View guidelines and instructions here.

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