NeuroFutures 2017: Brain connectivity in health and disease, July 9–11

Join some of the brightest minds in research, engineering, industry and clinical domains at NeuroFutures 2017. This year’s conference will focus on neuronal circuits, with topics including novel imaging approaches, brain clearing and expansion techniques, human and non-human primate circuit function, genetically engineered probes for circuit function, circuits in degeneration, and circuits in psychiatric disorders.

UBC
NeuroFutures 2017

July 9-11, 2017

 

University of British Columbia
Vancouver, Canada

Gary Marcus, Ph.D., director, NYU Center for Language and Music, and professor of psychology, New York University, will present a public lecture, “What artificial intelligence can learn from the brain, and vice versa.” Keynote addresses will be given by Loren Looger, Ph.D., group leader, Janelia Research Campus, Howard Hughes Medical Institute, and Brian MacVicar, Ph.D., co-director, Djavad Mowafaghian Centre for Brain Health, University of British Columbia. Looger will present “Genetically engineered indicators of neuronal activity.” MacVicar will present “Imaging metabolism using fluorescence lifetime.”

NeuroFutures 2017 is sponsored by the University of British Columbia, OHSU, Leica Microsystems, the Allen Institute for Brain Science, the University of Washington, and the University of British Columbia. Following the conference, there will be a brain clearing and expansion workshop on July 12.

Registration and agenda information is available at the NeuroFutures website.

Sex matters: OHSU researchers shine light on mechanisms of ischemic stroke

Regulatory T cells are increased in the spleens of female mice.

Regulatory T cells are increased in the spleens of female mice.

Sex—like age, weight, and underlying health conditions—is a biological variable that is often a critical factor when it comes to health. However, sex has been largely absent in research and this has led to an incomplete understanding of sex-based differences in disease processes and treatment therapies that are appropriate for men and women.

Ischemic stroke is one of the diseases for which a lack of preclinical data on male and female subjects presents a critical gap in information for clinical researchers who are testing therapies in women and men.

A new study led by Halina Offner, Dr. Med., shines some light on the ways immune systems in female and male mice respond differently to ischemic stroke. The study was published in Cellular Immunology. Offner, OHSU professor of neurology, and immunologist at the Veterans Affairs Medical Center, and her team see this as an important step in developing effective treatments. In this case, successful therapies will be sex-specific.

Investigators examined the integration of the spleen—a major component of the immune system—in the regulation of immune responses in the brain and throughout the body. The severity of the stroke was measured using digital imaging, and levels of immune-related cells were measured and analyzed with a Cellometer cell counter and flow cytometry analysis.

The study demonstrated two important differences in immune regulation in male and female mice. Female mice had higher levels of regulatory B cells, which help suppress responses, but had lower levels of anti-inflammatory macrophages, another immune cell. These results make clear mechanisms that account for less severe strokes in females and also explain why immune modulating therapies, like splenectomy, protect male animals but not female animals.

This research, supported by a 2012–2016 NIH grant, underscores the importance of testing therapies for stroke in both males and females. Beginning in January, 2016, the NIH began ensuring that researchers account for sex as a biological variable in studies with vertebrate animals and humans. Closing the gaps in preclinical knowledge will provide scientific data to help improve treatments and recovery of women and men.

 

In addition to Offner and first author Hilary Seifert, Ph.D., (log-in required) co-authors include Gil Benedek, Jian Liang, Ha Nguyen, Gail Kent, Arthur Vandenbark, and Julie Saugstad. This work was supported by NIH/National Institute of Neurological Disorders and Stroke 1RO1 NS075887 (H.O.) and 1RO1 NS076013 (H.O., J.S.) and the American Heart Association 17GRNT33220001 (H.O). 

OHSU researchers: New discovery on obesity-high blood pressure relationship

Obesity contributes to high blood pressure, but why and how this happens remains unclear. One of the major causes of high blood pressure—or hypertension—is the inappropriate activation of the fight-or-flight sympathetic nervous system response, and most obesity researchers have focused on factors that increase sympathetic activity. Virginia Brooks, Ph.D., however, has been investigating mechanisms that inhibit this activity.

Model illustrating proposed neurocircuitry by which NPY neurons inhibit sympathetic nerve activity.

Model illustrating proposed neurocircuitry by which NPY neurons inhibit sympathetic nerve activity.

A team led by Brooks, professor of physiology and pharmacology at OHSU, identified a neuromodulator, neuropeptide Y (NPY), that inhibits sympathetic activity in a specific area of the hypothalamus, the paraventricular nucleus. They found that withdrawal of that inhibition is required for an increase in sympathetic activity to occur in certain conditions, like obesity. However, the sources of NPY inhibition to the paraventricular nucleus were unknown.

To investigate the blood pressure effects of NPY neurons, the team used designer receptors exclusively activated by designer drugs (DREADDs) to selectively activate or inhibit these particular neurons in another hypothalamic nucleus, the arcuate, in mice. They demonstrated that the same population of neurons that increases feeding also suppresses blood pressure. Brooks and senior research associate Zhigang Shi, Ph.D., have published their findings that both verify that NPY inhibits sympathetic activity and also identify a new hypothalamic site and neuronal pathway by which NPY suppresses that activity. The paper was published in the Journal of Clinical Investigation.

DREADDs, along with three concurrent technical accomplishments by Shi, made the experiments possible. He may have been the first person to successfully secure an electrode around the sympathetic nerve of a mouse, place a cannulae in blood vessels so the team could measure blood pressure and deliver infusions, and conduct nanoinjections using micropipettes with tips that were about 20 micrometers—the size of a couple of neurons. With these, he was able to inject treatments into the paraventricular nucleus, an area of the brain smaller than a ballpoint pen, while simultaneously measuring sympathetic nerve activity.

Neuropeptide Y antagonists are primary targets in the development of drugs for obesity and anxiety disorders, often without consideration of the effects on blood pressure. In addition to helping develop better drugs to treat high blood pressure in obese patients, research conducted in Brooks’ lab might help to understand the potential cardiovascular side effects of anti-obesity treatments.

Along with Brooks and Shi, Christopher Madden, Ph.D., coauthored the paper. This research was funded in part by NIH grants HL088552 and HL128181 (VLB), AHA15POST23040042 postdoctoral fellowship (ZS), ADA 1-13-BS-120 (CJM), and NINDS P30 NS061800 (PI, S. Aicher).

New bioinformatics services for all OHSU investigators available

Fee-for-service bioinformatics support, focused on next-generation sequencing, became available to all OHSU investigators on July 1, 2017.

cellsThis interim bioinformatics service will provide additional capacity and will complement the existing Oregon National Primate Research Center bioinformatics service core, which is primarily dedicated to ONPRC investigators, as well as the bioinformatics services provided for Knight Cardiovascular Institute Epigenetics Consortium members.

Investigators will have two new tiers of bioinformatics service available to them: (1) flat-fee based QA/QC and alignment, and (2) hourly rate analytical support. In addition, the Oregon Clinical and Translational Research Institute (OCTRI) Translational Bioinformatics Program will provide consultations regarding experimental design, data management and dissemination free of charge for FY18.

In order to assess the growing needs of OHSU investigators, the OCTRI Translational Bioinformatics Program will provide a unified point of contact and will connect investigators with available faculty collaborators from across campus for other bioinformatics needs (imaging, proteomics, immunophenotyping, natural language processing, etc.). Available collaborators are found in the Division of Bioinformatics and Computational Biomedicine in the Department of Medical Informatics and Clinical Epidemiology, Department of Biomedical Engineering, the OCTRI Biostatistics and Design Program (BDP), the OCTRI Research Data Warehouse, the OHSU-PSU School of Public Health Biostatistics, the Knight Cancer Institute Biostatistics Shared Resource, and other OHSU units.

The data collected by OCTRI Translational Bioinformatics Program and the MPSSR on support requests and utilization of these services will be critical to guide the university in the expansion of existing cores as well as the development of new ones. In particular, these data will help us restart a new bioinformatics core for OHSU if the demand shows its necessity.

This fee-for-service bioinformatics support has been made possible by a partnership between the Office of the Senior Vice President for Research, the University Shared Resources (USR) program, the OCTRI Translational Bioinformatics Program, the Integrated Genomics Laboratory’s Massively Parallel Sequencing Shared Resource (MPSSR) and the Advanced Computing Center (ACC).

For a free consultation or to request analytical support, please submit a service request. MPSSR users will also be able to request services when they initiate projects via the MPSSR’s online form at the OHSU iLab portal.

 

 

 

Upcoming class: Introduction to Research Administration, July 13

Research Administration Training & Education (RATE) connects the research community with workplace learning and offers classes for research administrators and others who support research at OHSU.

RDA 101 provides a big-picture overview of research administration. Meet Research Development and Administration unit leaders, tour valuable web resources, and meet face-to-face with your contacts in OPAM, IRB, TTBD, and others.

RDA 101: Introduction to Research Administration
Thursday, July 13
9:30 to 11:30 a.m.
Center for Health & Healing, CHH 3070, room 4

The class is designed for research administrators who are new to OHSU, as well as those who have been at OHSU for a while.

Use your network login to enroll through Compass. Questions? Contact Margaret Gardner.

K12 career development opportunity for research in women’s health, sex/gender differences

BIRCWH logo

The BIRCWH (Building Interdisciplinary Research Careers in Women’s Health) K12 program announces a special funding opportunity for OHSU junior faculty members. The BIRCWH program provides salary support and fringe benefits, limited research funding, and an infrastructure to support mentored career development for those interested in interdisciplinary basic, translational, behavioral, clinical, population, and/or health services women’s health and/or sex/gender differences research. The BIRCWH program anticipates up to three openings for a K12 scholar in Fall of 2017 and Winter of 2018. Deadline for applications is August 1, 2017.

Award information: Scholars will receive salary and fringe benefit support for .75 FTE, up to $93,000 (plus OPE), and up to $25,000 per year for research, supplies, and travel. You will be appointed as an OCTRI scholar, which will give you access to core OCTRI services including statistics, IRB, regulatory compliance etc. (Some limitations will apply to these services.) This is an interdisciplinary research training program, so scholars must have multiple, experienced research mentors who represent different disciplines.

Eligibility: Applicants must be U.S. citizens or non-citizen nationals, or individuals lawfully admitted for permanent residence (by October 1, 2017), who hold a clinical or nonclinical doctoral degree or its equivalent, can commit a minimum of 75% full-time professional effort to conducting women’s health and/or sex/gender differences research, have identified mentors with extensive research experience, and must NOT be or have been a PI on an R01 or K award. The applicant’s department must commit to support for a faculty appointment, protecting 75% FTE for research on this award, and covering any excess salary/OPE beyond this award.

Visit the BIRCWH website for more information. Apply here.

For questions or for more information, please contact BIRCWH Program Director Jeanne-Marie Guise, MD, MPH or BIRCWH Program Coordinator Daniel Johnson.

Outgoing Subawards: Best practices, West Campus, June 27

Does your research department subcontract with third parties for projects or programs? Research Administration Training & Education (RATE) offers a number of learning opportunities at South Waterfront, Marquam Hill and West Campus locations. In June, we are offering Outgoing Subawards: Best practices.

Outgoing Subawards: Best practices
Tuesday, June 27
1 to 2 p.m.
VGTI Conference Room, 1st floor
West Campus

Meet the Sub-out team and gain insight into best practices for development and administration of subawards. Course topics include tips for completing required documents to avoid administrative hang-ups; creating a subaward scope of work and budget; and potential pitfalls in sub-out requests and how to avoid them.

Part instruction and part discussion, this session is intended for departmental staff who coordinate or manage administrative aspects of subaward or subrecipient relations and processes.

To find more information and to enroll, visit Compass, or contact the RATE Program team at rate@ohsu.edu.

Applying for foundation funding? Check out the President’s List!

Just a friendly reminder that if you plan to submit a grant to a foundation or corporation on the OHSU President’s List, you are required to submit a Notice of Intent form to the OHSU Foundation. The purpose of the President’s List is to ensure that OHSU maintains coordinated communication with these organizations. Additionally, some organizations are reserved for top institutional priorities as determined by senior OHSU leadership.

Things to keep in mind:

  • If you’re interested in applying to one of these organizations, please submit a Notice of Intent form. The Notice of Intent Form is only required for organizations on the list.
  • If Office of Proposal & Award Management needs to contact one of these organizations or receives communications from them, please let someone on the Office of Foundation Relations team know.
  • The OHSU President’s List is updated about once a year.

Questions? Contact the OHSU Foundation.

Searle Scholars career development program; internal deadline July 12

The Searle Scholars Program is a highly competitive program designed to support exceptional, new junior faculty. It supports research in biochemistry, cell biology, genetics, immunology, neuroscience, and pharmacology, as well as related areas in chemistry, medicine, and the biological sciences. The program does not ordinarily support purely clinical research but has supported research programs that include both clinical and basic components. Applications are evaluated on the potential of the applicant to make innovative and high-impact contributions to research over an extended period of time. Awardees receive $100,000 per year for three years.

Candidates should have begun their first appointment as an independent investigator at the assistant professor level on or after July 1, 2016. The appointment must be a tenure-track position (or its nearest equivalent).

Internal deadline: July 12, 2017
Sponsor deadline: September 29, 2017

Limited SubmissionThis opportunity requires internal coordination because OHSU is limited to only submit one application. If you intend to apply, complete an application via Competitive Application Portal (CAP) by the internal deadline. Click here to learn more about OHSU’s Limited Submission process.

Arthur Vandenbark and team find treatment dose for MS is sex dependent

High dose of DRα1-mMOG-35-55 reduces demyelination and leukocyte infiltration in female mice with chronic EAE.

High dose of DRα1-mMOG-35-55 reduces demyelination and leukocyte infiltration in female mice with chronic EAE.

One of the main challenges in treating multiple sclerosis is reversing the effects of accumulated damage to the central nervous system. Damage to myelin, which coats and protects axons, and chronic axonal loss due to the absence of myelin are hallmarks of the disease. Most of the available drugs for MS are anti-inflammatory and used to treat the most common type of MS: relapsing-remitting. It is not clear to what extent these drugs help repair damaged axons and create new myelin sheaths. Repairing or stopping chronic myelin damage may reduce or halt MS progression.

A team led by Arthur A. Vandenbark, Ph.D., used a mouse model of MS to evaluate potencies of a genetic therapy, called pMHC class II constructs, on the progressive form of this MS model. Vandenbark, professor in the OHSU Multiple Sclerosis Center, and his team have previously shown that these pMHC class II constructs may prevent or reverse clinical signs of neuro-inflammatory diseases, including the mouse model of MS.

The research, published May 6 in the Journal of Neuroinflammation, demonstrated that treating the mouse model of chronic MS with these constructs significantly reversed the clinical severity of the disease. The treatment also reduced continued loss of myelin and the associated axonal damage in the central nervous system.

The findings demonstrated that the effective dose of pMHC constructs was sex dependent and might be regulated by estrogen signaling through estrogen receptor alpha, a nuclear receptor that is activated by the sex hormone estrogen. The team identified the importance of the dose of these constructs, particularly when used in future therapies for women with progressive MS. Of the 400,000 people in the United States with MS, most are women.

This work may potentially support the design of future clinical trials using pMHC for treatment of progressive MS.

In addition to Vandenbark and first authors Gil Benedek and Priya Chaudhary, co-authors include Roberto Meza-Romero, Evan Calkins, Gail Kent, Halina Offner, and Dennis Bourdette.

This work was supported by NIH grants AI 122574 (to AAV) and the Merit Award BX000226 (to AAV) through the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development.

 

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