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.

New NIH application guidelines: Changes to appendix and post-submission materials policies

NIH has released an updated application guide that includes two significant policy changes effective Jan. 25, 2017.

1) As we reported earlier this year, most appendix materials for applications have been eliminated. The only materials you may submit in the appendix section are:

For applications proposing clinical trials (unless the FOA provides other instructions for these materials):

  • Clinical trial protocols
  • Investigator’s brochure from Investigational New Drug (IND), as appropriate

For all applications:

  • Blank informed consent/assent forms
  • Blank surveys, questionnaires, data collection instruments
  • FOA-specified items. If appendix materials are required in the FOA, review criteria for that FOA will address those materials, and applications submitted without those appendix materials will be considered incomplete and will not be reviewed.

Note: Papers and manuscripts are no longer acceptable as appendix materials.  Applications submitted with other appendix materials than those listed above will be withdrawn.

2) Current NIH and AHRQ policy concerning post-submission materials has been consolidated and simplified. This applies to materials that are submitted after the grant application has been submitted but prior to peer review.  The new policy reflects the guiding principle that post-submission materials will only be accepted if they’re the result an unforeseen event. The policy does not allow for submission of materials to correct oversights or errors discovered after the application submission.

The full announcement outlines allowable post-submission materials for all applications as well as those specific to T, F, and K series applications. Detailed requirements for submitting these materials are also provided.

 

Upcoming OCTRI classes and presentation

Oregon Clinical & Translational Research Institute hosts classes and presentations for the OHSU research community. Next on the calendar are Epic for Research and Excel for Research.

Epic for Research
This class will cover a range of features in Epic, from identifying potential subjects to obtaining data for analysis. Panelists will discuss how Epic can support your research project.

Monday, Dec. 5
12 to 1p.m.
OHSU Hospital, 8th floor auditorium

Thursday, Feb. 23
12 to 1 p.m.
Center for Health and Healing 3181, room 1B

Speakers: Rachel Navarro from the Epic Research Team and Rob Schuff from the bioinformatics group at Oregon Clinical & Translational Research Institute

Excel for Research
This presentation will discuss best practices for managing data in Excel for research.

Thursday, Jan. 12
12 to 1 p.m.
Center for Health and Healing 3181, room 1B

Speaker: Julie Mitchell, Operations Manager, Oregon Clinical & Translational Research Institute

Registration is not required. Questions? Contact Kitt Swartz.

New study documents role of glial cells in brain

GCaMP6s expression

Expression of protein calcium sensors in astrocytes and traces of 10 individual astrocytes from an intact larva.

Glial cells, once considered passive bystanders of neural transmission, are now understood to provide support and protection for neurons in the central and peripheral nervous systems. Astrocytes, the most abundant glial cells in the brain, closely associate with neuronal synapses and perform supporting roles in neuronal activity by providing oxygen and sugars and by removing carbon dioxide. New research findings demonstrate a function scientists have proposed but not proven — that astrocytes not only support but actively participate in processing information in the brain.

A team of scientists led by Marc Freeman, Ph.D., director of the Vollum Institute, documented in fruit flies a newly understood pathway for transmitting signals within the brain. The research, published in the journal Nature, provided the first in vivo demonstration of astrocyte calcium signaling as essential for behaviors such as olfactory or startle responses.

The team demonstrated that neurons release neurotransmitters that bind astrocytes and change astrocyte calcium signaling, which then regulates downstream neurons. These findings make possible opportunities for the development of new, targeted therapies for regulating a wide range of neurological functions in humans, from hunger to mood.

The scientists will next investigate the extent of this type of signaling in the brain, as well as the influence of astrocytes on neuromodulators such as dopamine or serotonin.

Freeman authored the study while a professor and vice chair of the Department of Neurobiology at the University of Massachusetts Medical School and investigator in the Howard Hughes Medical Institute. Co-authors include Zhiguo Ma and Tobias Stork of the Howard Hughes Medical Institute and Dwight E. Bergles of Johns Hopkins University School of Medicine.

The work was supported NINDS grant R01 NS053538.

Read the full OHSU news release.

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