Motor neurons aren’t the only site for restoring locomotive function

TBPH mutant larvae show defective motor behavior, which can be rescued by 654 cacophony expression in selected neurons.

TBPH mutant larvae show defective motor behavior, which can be rescued by 654 cacophony expression in selected neurons.

Amyotrophic lateral sclerosis is the most common adult onset motor neuron disease for which there is no cure or treatment that significantly extends life. ALS causes the death of neurons that control voluntary muscles and is characterized by gradually worsening weakness, loss of motor function and, when the individual can no longer breathe, death. The only FDA-approved drug used to treat ALS prolongs on average the lifetime of a patient by two to three months.

A feature in neurodegenerative diseases, including about 90 percent of patients with ALS, is a mutation in the transactivating responsive sequence DNA-binding protein (TDP-43). Neurons are known to be sensitive to TDP-43 expression levels, but the specific defects caused by TDP-43 loss of function have not been described in detail.

Now, in a paper published in the Journal of Neuroscience, a team led by David Morton, Ph.D., has demonstrated that function can be restored by increased expression of a single gene in two central neurons. Conducted in the lab of Morton, professor of integrative biosciences and associate dean of research in the School of Dentistry, the research expanded on Morton’s 2013 discovery that expression of a voltage gated calcium channel restored the loss of motor function in a fruit fly model of ALS.

The team hypothesized that the mechanisms by which TDP-43 expression restores motor function would take place in motor neurons. Kayly Lembke, lead author and graduate student in the Department of Physiology and Pharmacology, found that, in addition to motor neurons, expression of a voltage gated calcium channel in two central neurons in the brain are able to restore motor defects.

The finding that such a small number of neurons—two—can restore motor function is significant. TDP-43 regulates a large number of other genes and, if restoration required a significant number of processes, it would be extremely challenging to target any one of the processes. The discovery that expressing this channel can restore function opens the future possibility of therapeutic strategies that target this channel. This possibility, however, will require substantially more work.

The next step is developing a more targeted model.

 

This study was supported by grants from NINDS (NS071186) and the ALS Association. The OHSU Sequencing and Bioinformatics Cores provided analysis and sequencing for the study.

Eric Smith named director of OHSU Clinical Research Support Office

Eric SmithEric Smith, M.S., M.B.A., has been named the director of the OHSU Clinical Research Support Office. The CRSO was launched on July 3, 2017, in order to bring clinical research support functions under one umbrella and focus on partnering with the research community to support OHSU’s clinical research leadership.

Smith comes to this position from the OHSU School of Medicine’s Department of Dermatology, where he has served since 2011 as associate director of translational research and dermatopathology, and as administrator of the Knight Cancer Institute melanoma program. Before coming to OHSU, he held leadership roles at the University of Utah. Smith holds a master’s of business administration and a master’s in science and technology in biotechnology, both from the University of Utah. He brings knowledge and experience in clinical and translational research, program development, process improvement, and operational excellence to this new role.

As director of the Clinical Research Support Office, he will focus on service, transparency, and improving response times, in balance with risk assessment and regulatory requirements.

Smith will report to the vice president for research operations with joint reporting to the associate vice president for clinical and translational research and will work closely with key programs and units within the Oregon Clinical & Translational Research Institute. He will transition to his new role beginning October 2, 2017.

Welcome: Grace Phelps Distinguished Professor

michelle-van-rynWelcome to Michelle van Ryn, Ph.D., who has been appointed professor and Grace Phelps Distinguished Professor at the OHSU School of Nursing. She comes to OHSU from the Mayo Clinic in Rochester where she was professor of health services research and director of the Research Program on Equity & Inclusion in Healthcare. She is also the founder and lead scientific advisor of the Institute for Equity & Inclusion Sciences, a public benefit corporation whose mission is to translate current evidence into practical and effective approaches for achieving equity, and deep diversity and inclusion.

Dr. van Ryn’s research focuses primarily on the way “invisible actors,” such as informal organization norms/diversity climate, implicit (unconscious) biases, inter-group anxiety, and stereotype affect social interaction processes and decision-making. The ultimate goal of her work is to ensure all patients, clients, and students receive equally high-quality care, services, and education in fully inclusive organizations. Her research has improved the national awareness of how providers contribute to disparities in patient care and has led to greater understanding of how improved health care encounters positively impact patient outcomes. She has given more than 75 invited presentations on her research, both nationally and abroad, and she has authored over 107 journal articles, abstracts, and other written publications.

The Grace Phelps Distinguished Professorship
In 1915, after completing a graduate course in hospital management in San Francisco, Grace Phelps assumed the directorship of the Multnomah School for Nurses. Grace came to Portland in 1909 from the Cincinnati City Training School for Nurses and worked at Multnomah County Hospital where she was active in civic affairs. Her civic network included nurses and non-nurses. Prior to accepting the director’s position, she was instrumental in establishing the Oregon State Graduate Nurse Association (1904), worked to pass the Nurse Registration Act (1911), and was a recipient of the Oregonian’s “Citation of the Week” for her many contributions. Grace Phelps was an early advocate of collegiate education for nurses and the establishment of the department of nursing education at the University of Oregon, now the OHSU School of Nursing.

Originally published on the OHSU School of Nursing blog (password required).

Traumatic Brain Injury Symposium: From Research to Recovery, Sept. 15–16

The OHSU Brain Institute will host the annual Traumatic Brain Injury Symposium: From Research to Recovery on September 15 and 16, 2017. The focus on day one will be the neuroscience research of concussion and recovery. The second day will feature breakout sessions on the latest evaluation techniques and treatments for concussion. Participants are encouraged to attend both days, as well as a poster reception Friday evening.

OBI researchTBI Symposium: From Research to Recovery
Friday, Sept. 15, 2017
1 – 6:00 p.m.
OHSU Auditorium/Old Library

Saturday, Sept. 16, 2017
7:30 a.m. – 12:00 p.m.
OHSU School of Nursing

The Symposium features two keynote speakers. Jamshid Ghajar, M.D., Ph.D., director of the Stanford Concussion and Brain Performance Center, will present a research-focused lectured on the role of dynamic visual orientation in concussion. Stanley A. Herring, M.D., clinical professor at the University of Washington, will provide a Berlin Guideline update to the clinicians.

Registration information and a full agenda can be found here.

2017 Flux Congress hosted in Portland Sept. 16-18; Damien Fair to receive Young Investigator Award

Damien-Fair

You’re invited to join the OHSU Department of Behavioral Neuroscience in Portland at the international meeting of Flux: The Society for Developmental Cognitive Neuroscience, September 16–18, 2017.

Damien Fair, P.A.-C., Ph.D., will be presented with the Flux Society Young Investigator Award at the event. Fair, an associate professor in the Behavioral Neuroscience Department, focuses his research on the mechanisms and principles that underlie the developing brain.

The 2017 Flux Congress opens with the Translational Neuroscience Symposium, chaired by Bita Moghaddam, Ph.D. Moghaddam, Ruth Matarazzo Professor and chair of the Department of Behavioral Neuroscience, will deliver a presentation on recent behavioral and electrophysiological studies that describe differences in reward processing between adolescence and adulthood and their influence on cognition. Brian O’Roak, Ph.D., assistant professor of molecular and medical genetics in the School of Medicine, will present on the rapidly accelerating pace of autism genetics as a model for genetic studies in mental health. Bonnie Nagel, Ph.D., associate professor of psychiatry in the School of Medicine, is the symposium discussant. Stephen Boyd, postdoc in the Developmental Brain Imaging Lab, will present a flash talk on the nucleus accumbens and its potential relationship to adolescent drinking.

2017 Flux Congress
Saturday, Sept. 16 – Monday, Sept. 18
Hilton Portland, Portland OR

The OHSU Department of Behavioral Neuroscience and the Office of the Senior Vice President for Research are sponsors of the Flux Congress. Scientists, principal investigators, postdocs, and students are invited to attend.

OCTRI receives $37 million grant from the National Center for Advancing Translational Sciences

The National Institutes of Health has named OHSU’s Oregon Clinical & Translational Research Institute a recipient of 2017 Clinical and Translational Science Award (CTSA) grant. OCTRI was an original recipient of the program in 2006, and the new award provides more than $37 million in federal funding to support the Institute’s work over the next five years.

OCTRI helps accelerate the translation of research into clinical use, medical practice and health policy, with the goal of improving the health of the public.

“Our support for clinical trials, translational science, pilot studies, career development and study design has made OCTRI an integral part of the OHSU research community,” said David Ellison, M.D., director of OCTRI. “We look forward to continuing this important work with OHSU investigators.”

The OCTRI Scholar Program helped support Rebecca Spain's recently published research on the effects of lipoic acid on multiple sclerosis. OCTRI study coordinators, nursing and informatics resources and regulatory support contributed to the study.

The OCTRI Scholar Program helped support Rebecca Spain’s recently published research on the effects of lipoic acid on multiple sclerosis. OCTRI study coordinators, nursing and informatics resources and regulatory support contributed to the study.

OCTRI career development initiatives have educated more than 600 young investigators since 2006. The initiatives include the KL2 Mentored Career Development program for faculty scholars and the TL1 program for predoctoral and postdoctoral training in translational research.

Pilot study funding from OCTRI supports innovation and collaboration. The Biomedical Innovation Program, an OCTRI collaboration with OHSU Technology Transfer and Business Development, provides funding up to $60,000, project management, and access to project-specific mentors and experts. The new Team Science Awards will help advance novel, collaborative research initiatives at OHSU.

OCTRI supports human subjects research through the Clinical and Translational Research Center, with a full range of research support, including informatics services, data management and analysis, and regulatory assistance. The recently formed Clinical Research Development Team provides assistance to investigators with integrated protocol design support, rapid study start-up, recruitment consultation, and solution-based support of ongoing research.

OCTRI is also a key partner in a new CTSA collaborative initiative—the Trial Innovation Network. TIN provides resources and infrastructure for investigators planning and conducting multi-site research, including support for single IRB and master contracting models. The goal is to not only execute trials better, faster and more cost-efficiently as part of a national laboratory to study, understand and innovate the process of conducting clinical trials.

The CTSA program’s renewed funding provides OCTRI with the resources to expand its services, education, and mentorship to OHSU investigators.

When and how to request an urgent IRB review

Submissions for IRB review are typically reviewed in the order in which they are received. However, there are situations that require more urgent attention.

 Examples of these are:

  • Subjects are critically ill and awaiting IRB approval of an initial submission or modification.
  • Imminent funding deadline (e.g., NIH just-in-time notifications).
  • Projects with tight timelines, such as a summer student research project.

In urgent cases, please take the following steps:

  1. Ensure your submission is complete and accurate to avoid the delay in having it returned to you for corrections.
  2. Prepare and submit the project as quickly as possible.
  3. Use the ‘Add Comment’ function in the eIRB to request an urgent review and route to the “IRB Coordinator” by marking that checkbox before submitting your comment. 
  4. Email the IRB at irb@ohsu.edu to inform their office of your request, indicating in the subject line that it is an urgent review request.  If possible, include the IRB number with a hyperlink in the body of the email and describe the rationale for the request. 

 

For more information, please visit the IRB Review page. Please email Research Integrity at irb@ohsu.edu with any questions.

New findings show retinal development requires the protein dystroglycan

Dystroglycan is required to localize ECM proteins at the ILM.

Dystroglycan is required to localize ECM proteins at the ILM.

OHSU scientists have published a paper that provides new information on retinal development and visual system abnormalities present in dystroglycanopathy, a form of muscular dystrophy that results from defective function of the protein dystroglycan.

Patients with severe forms of dystroglycanopathy frequently experience visual system problems in addition to other neurodevelopmental abnormalities. There is some understanding of dystroglycan’s influence on brain development, but its role in regulating retinal development has remained poorly understood. A team led by Kevin Wright, Ph.D., an assistant professor at the Vollum Institute, has published findings in the Journal of Neuroscience that provide new insight into the mechanisms of dystroglycan function in the retina using a mouse model of dystroglycanopathy.

Reena Clements, a neuroscience graduate student in the Wright lab, demonstrated that dystroglycan is required for maintaining the structural integrity of the inner limiting membrane in the developing retina. The team found that in the absence of functional dystroglycan, this membrane, which separates the retina from the vitreous, begins to degenerate. Breaches that form in the membrane allow neurons to migrate into the vitreous space, disrupting the highly organized structure of the retina.

These results demonstrate that disorganization of retinal circuit development is a likely contributor to visual dysfunction in patients with dystroglycanopathy. The findings in the eye are similar to what previously has been seen in the brain, suggesting a critical role for dystroglycan that is conserved throughout the developing nervous system.

 

In addition to Wright and Clements, coauthors include Rolf Turk, Ph.D., and Kevin P. Campbell, Ph.D. 

This work was supported by the National Institutes of Health (R01-NS091027 (K.M.W.), the Whitehall Institute (K.M.W.), the Medical Research Foundation of Oregon (K.M.W.), the National Science Foundation Graduate Research Fellowship Program (R.C.), a LaCroute Neurobiology of Disease Fellowship (R.C.), a Tartar Trust Fellowship (R.C.), the National Institute of Neurological Disorders and Stroke (P30-NS061800 to the OHSU Advanced Light Microscopy Core), and the Paul D. Wellstone Muscular Dystrophy Cooperative Research Center (1U54NS053672 to K.P.C.). 

 

 

INVENT: Accelerating innovation and commercialization

Invent-Workshop-9.20This INVENT workshop helps early-stage startups establish effective financial strategies to attract potential investors and maintain a positive overall financial standing.

Building a winning financial model for your startup

Susan Preston, manager of the Seattle Angel Fund, will discuss:

  • The importance of a sound financial model
  • Variables to include in your financial model
  • The impact and influence of your financial model on your business plan
  • How your financial model ties into your value proposition

Wednesday, Sept. 20, 9–11 a.m.
Urban Office, 4949 S.W. Macadam Ave.
Portland, OR 97239

Join the Oregon Clinical and Translational Research Institute, Technology Transfer and Business Development, and the OTRADI Bioscience Incubator for this interactive workshop.

Admission is free, RSVP is encouraged as seating is limited.

Questions? Contact Jonathan Jubera at jubera@ohsu.edu

 

Study suggests cosmic rays pose long-term risks for astronauts

Unsupervised K-means clustering reveals distinct patterns of 5hmC and 5mC regulation.

Unsupervised K-means clustering reveals distinct patterns of 5hmC and 5mC regulation.

For astronauts on long missions in deep space, the brain’s response to radiation exposure is an important concern. Cognitive and other impairments put crews at risk during space travel and may pose significant health hazards to space flight crews for years after a mission.

A unique feature of the space radiation environment is the presence of galactic cosmic rays and solar particle events, both of which involve protons. Exposure to these will likely impact multiple organ systems. In the central nervous system, radiation exposure significantly affects the hippocampus, which is critical for memory function.

A team of OHSU scientists led by Jacob Raber, Ph.D., and including Soren Impey, Ph.D., and Mitchell Turker, Ph.D., has demonstrated that the brain’s response to proton irradiation is both specific and prolonged. Using a mouse model, the scientists found impairments in object recognition, spatial memory retention, and hippocampal network stability after proton irradiation.

This research, published today in Scientific Reports, builds on previous research conducted by Raber, a professor of behavioral neuroscience, neurology and radiation medicine, and OHSU colleagues Impey, an associate professor of pediatrics and member of the Oregon Stem Cell Center, and Turker, a professor in the Oregon Institute of Occupational Health Sciences. In a paper published in 2016, they reported that long-term exposure to cosmic radiation may have the potential to alter the brain and change behavior in astronauts bound for Mars. That research project tested short- and long-term effects of radiation with Iron-56 ions on 6-month-old mice. In the new research, the cognitive changes observed after two weeks overlapped significantly with the impairments that continued at week 20—the alterations to the DNA did not disappear. In this research, mice were exposed to irradiation at the NASA Space Radiation Laboratory at Brookhaven National Laboratory in Upton, New York. The NSRL facility simulates the cosmic radiation astronauts would experience in deep space.

Proton irradiation is also clinically relevant, as it is increasingly used in cancer therapy. Cognitive impairments due to radiation or chemotherapy, commonly called “chemo brain,” can be significant following treatments for cancer. Continued research on the ways in which cosmic rays affect the brain may help protect not only long-distance space travelers during and following missions, but cancer survivors as well.

 

This work was supported by NASA grant NNJ12ZSA001N. Robert Searles, Ph.D., director of the Massively Parallel Sequencing Shared Resource provided expertise for the design and interpretation of the DNA methylation and RNAseq experiments in the study. 

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Welcome to the Research News Blog

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