AHRQ seeking science on treatment-resistant depression

The Agency for Healthcare Research and Quality is looking more closely at why some patients diagnosed with depression don’t respond to treatment. Currently, there is scant data on the prevalence of treatment-resistant depression, and a thorough review of the research that exists hasn’t been conducted. So AHRQ is embarking on a review of both ongoing and published studies of treatment-resistant depression. Specifically, they’re looking at how the condition is defined, what populations have been studied, and which drugs have been tested.

Have a study you’d like to submit? Do so here by March 31, 2017.

Research Week 2017: Call for abstracts, due Mar. 7

FPP 21469239 Research Week 2017 ART RGBStudents, faculty, research-ranked employees, postdocs, and staff are invited to submit abstracts for an oral or poster presentation at OHSU Research Week, May 1-3, 2017.

Research Week is a university-wide event that celebrates the excellence of research performed across all schools, centers, institutes, and education programs at OHSU. It’s a unique opportunity to get out of the lab or clinic and meet colleagues from various disciplines.

Visit the Research Week Call for Abstracts page for complete instructions on how to submit. You may also go directly to the submission tool. Abstract submissions are due Tuesday, Mar. 7, 2017. Stay tuned to Research News for updates and information about the agenda, keynote speakers, pre-event skills workshops, and more.

Scholarships available to students presenting posters

A small pool of scholarship money is available for OHSU students who would like to present a poster at Research Week but who don’t have department support for poster printing expenses. Learn more by visiting the Research Week Call for Abstracts page.

Making all the data count for disease diagnosis and discovery

Diagnosing diseases is a tricky business requiring a formidable breadth and depth of knowledge and the skill to apply it. The rarer the disease is, the harder it can be to diagnose: quality reference data may not exist and a physician might only see one such patient in her entire career. According to the National Institutes of Health, there are between 6000 and 7000 rare diseases affecting from 25 to 30 million Americans, making it likely that most, if not all, healthcare professionals have seen these patients in their practice but may not have known it. Oftentimes, a patient with a rare disease gets misdiagnosed as having a more common disease with a similar set of symptoms. In such cases, the misdiagnosis can lead to ineffective, or even harmful treatment; this is a danger even for patients who have rarer forms of a common disease. For a patient living with a rare disease, the mean time to diagnosis is 4.8 years and can take as long as 20 years. Moreover, the patient sees an average of 7.3 physicians during this time.

Melissa Haendel, Ph.D.

Melissa Haendel, Ph.D.

At OHSU, a team of researchers led by Melissa Haendel, Ph.D., associate professor in the Library and in the Department of Medical Informatics and Clinical Epidemiology, recently received two large grants to tackle grand challenges like these. The first grant is from the NIH Office of the Director to support OHSU’s ongoing efforts with the “Monarch Initiative,” and the second is through a novel award mechanism called the “BioMedical Data Translator” from the National Center for Advancing Translational Science (NCATS). These grants support the creation and application of software tools that combine data from multiple sources to help researchers and physicians accurately diagnose patients and better understand the underlying causes of their illness.

MonarchUsing Monarch funds, Haendel and colleagues will continue their work building a comprehensive database of disease signs and symptoms–linking that information to other types of data including clinical observations, patient genetics, and animal research. Many rare diseases have a suspected genetic cause that is so far unknown. Monarch is integrating data from diverse sources with the goal of uncovering the possible implicated genes which could aid the development of both diagnostics and treatments for patients.

OHSU’s Knight Diagnostic Lab Inherited Disorders group led by Sue Richards, Ph.D., has been using Monarch’s tools to support diagnosis of rare genetic diseases since 2015 with great success. “Whole exome sequencing generates datasets containing over 70,000 genetic variants. These tools have improved the efficiency and ability to find the “needle-in-the-haystack,” said Richards. The use of Monarch resources has ”..ended the diagnostic odyssey for a range of cases from neurological conditions to metabolic disorders.”

The Data Translator project aims to increase the breadth, connectedness, and accessibility of diverse data. One of the core components of the project is a data integration and modeling platform developed by Haendel’s group, described in their paper designated “breakthrough” in the Jan. 4, 2017 edition of Nucleic Acids Research. This freely available software resource has several possible applications: 1) A clinician who has a hard-to-diagnose patient could search for either known diseases with similar symptoms or for animal model research that could aid in the patient’s diagnosis, 2) A patient or researcher interested in learning more about a particular disease’s symptoms and all genes implicated with that disease, and 3) A researcher wanting to learn which  diseases are most similar to the manifestations seen in their model organisms.

“What is really surprising is how when you put data together from many different sources, you fill in knowledge gaps – it really is a story of the sum being greater than the parts with respect to discovering and understanding the causes of disease.” — Melissa Haendel

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More about this work. Haendel is a founding member of the Monarch Initiative (established 2012); the cross-disciplinary work of Monarch involves collaboration not only across groups within OHSU, but also with Lawrence Berkeley National Laboratory, The Jackson Laboratory, the University of Pittsburgh, Sanger Institute, Charité – Universitätsmedizin Berlin, Garvan Institute of Medical Research, and William Harvey Research Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London. A full list of the partnering organizations and the members of the team can be found at https://monarchinitiative.org/page/team. In addition to the Monarch consortium partners above, the NCATS Data Translator project also includes the team members from Johns Hopkins, Scripps Research Institute, Jackson Laboratory, and the Mayo Clinic; together they are combining their data and tools with other NCATS Translator awardees to advance our understanding of the genetic and environmental determinants of disease. Wherever possible, data and software generated by the consortium are open access and open-source; see the Monarch portal at https://monarchinitiative.org for more information.

 

OHSU researchers identify structure linked to insulin secretion

KATP channel gating model

KATP channel gating model

It was more than 30 years ago that an ATP-sensitive potassium (KATP ) channel was identified as the key molecular link between glucose metabolism and insulin secretion.

The KATP channels sense metabolic changes and translate these energy fluxes into channel gating, which adjusts membrane excitability and regulates insulin secretion. They are the targets of the sulfonylureas, antidiabetic drugs that increase insulin release from beta cells in the pancreas. Genetic mutations of the channel cause several devastating rare diseases characterized by abnormal blood glucose control and neurological symptoms.

It is known that KATP channels are a complex of two proteins, Kir6.2 and SUR1, which are uniquely dependent on each other for expression and function. Still lacking, however, is detailed structural information crucial to understanding how the two proteins assemble and function as a complex in order to regulate insulin secretion.

Now, OHSU scientists have obtained the first subnanometer structure of the channel, which reveals the detailed domain organization of KATP channels and the intricate structural interactions between SUR1 and Kir6.2. The research team, consisting of the lead author Gregory Martin, a student in the Graduate Program in Molecular and Cellular Biosciences, senior authors Show-Ling Shyng, Ph.D., and James Chen, Ph.D., of the Department of Biochemistry and Molecular Biology, as well as Craig Yoshioka, Ph.D. of the Department of Biomedical Engineering and Matt Whorton, Ph.D. of the Vollum Institute published their findings on January 16 in eLife journal.

Single-particle cryo-electron microscopy (cryo-EM) conducted at the OHSU Multiscale Microscopy Core was used to construct a three-dimensional map of the KATP channel assembly and gating. The structure revealed by this map shows how SUR1 and Kir6.2 work together and provides insight into how ATP and glibenclamide interact with the channel to block the channel, hence release of insulin.

The new insight gained from the structure lays the foundation for future structural and functional studies. In particular, structures bound with various stimulatory and inhibitory ligands will further advance understanding of the detailed mechanisms of channel gating. This knowledge will aid in the design of more effective drugs to treat several devastating diseases caused by defective KATP channels.

An interesting observation in this research is that the ATP binding cassette (ABC) core of SUR1 is in a twisted inward-facing conformation, which suggests a possible mechanism by which the antidiabetic drug glibenclamide inhibits KATP channel activity. Because glibenclamide is known to inhibit the activity of other ABC transporter proteins—including cystic fibrosis transmembrane conductance regulator (CFTR) and the multidrug resistance protein MDR—the mechanism proposed by Shyng’s team could have implications much broader than insulin secretion disorders.

The research was supported by National Institutes of Health grants R01DK066485 (to SLS) and F31DK105800 (to GMM) as well as by the OHSU Core Pilot Grant Program, which is funded by the University Shared Resources program and the Office of the Senior Vice President for Research.

Friends of Doernbecher research grant applications deadline extended, Feb. 17

Friends-of-Doernbecher-300x72Friends 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. The deadline to submit applications have been extended to February 17, 2017.

View program guidelines and application instructions here.

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

OCTRI announces 2017 Biomedical Innovation Program award recipients

The Oregon Clinical & Translational Research Institute has awarded three investigators grants through its Biomedical Innovation Program. The Biomedical Innovation Program aims to cultivate, select and provide strong program management for promising translational projects that develop new biomedical devices, diagnostics, and software. The primary objective of the program is to help bring innovative technologies from academia to the marketplace and thus to make a meaningful impact on human health.

The Biomedical Innovation Program is a collaboration between OCTRI and OHSU Technology Transfer and Business Development (TTBD), with additional funding and support from industry partners, Welch-Allyn and GE Healthcare.

Congratulations to our 2017 Biomedical Innovation Program Pilot Award Winners:

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David Huang, M.D., Ph.D., Peterson Professor of Ophthalmology, Professor of Biomedical Engineering 

Dry Eye Treatment Device (abstract pending)

 

 

david-sheridan_250
David Sheridan, M.D., Department of Emergency Medicine

Wearable Monitoring for Mental Health Patients

 

 

 

Simons
David Simons, M.D., Ph.D., Glaucoma Fellow, Casey Eye Institute

Glaucoma Tube Implant with Modulated Flow

 

 

 

 

“The Biomedical Innovation Program meets a critical need at OHSU by funding promising early stage and potentially marketable technologies,” said OCTRI Director David Ellison, MD. “This funding, along with project management and mentorship, helps move the needle substantially, to put these technologies in the best possible position for commercialization where they can ultimately improve patient outcomes. We are very excited to fund these new technologies for 2017, and look forward to working closely with the investigators.”

Detailed information on all three awards, including project abstracts, is on the OCTRI website.

 

 

Vaccine technology developed by OHSU researchers acquired by industry

Louis Picker, M.D., of the OSHU Vaccine and Gene Therapy Institute. (OHSU/Boone Speed Photography)

Louis Picker, M.D., of the OSHU Vaccine and Gene Therapy Institute. (OHSU/Boone Speed Photography)

OHSU researchers made international headlines in 2013 when they published findings that their HIV vaccine not only controlled SIV, the nonhuman primate form of HIV, but cleared it in nearly 60 percent of the monkeys in the trial.

The HIV vaccine—developed by of a team of scientists at the OHSU Vaccine and Gene Therapy Institute that includes Jay Nelson, Ph.D.; Klaus Frueh, Ph.D.; Scott Hansen, Ph.D.; and Louis J. Picker, M.D.—has shown such promise in pre-clinical trials that it is headed to phase 1 human clinical trials next year.

The vaccine platform is based on a unique model that uses the common herpes virus cytomegalovirus, or CMV, as the viral vaccine vector to deliver a knock-out blow to the various pathogens. Importantly, this platform is not limited to fighting HIV. It has the real potential to fight the world’s deadliest diseases, from tuberculosis and hepatitis B to malaria and papillomavirus.

The technology has now been acquired by Vir Biotechnology, a San Francisco-based biotech startup backed by the Bill & Melinda Gates Foundation and ARCH Venture Partners. The deal involves Vir buying TomegaVax Inc., an OHSU spinoff that holds the rights to the vaccine technology. This is a taken a critical step in translating a basic science concept pioneered at OHSU into a portfolio of commercial vaccines.

Research at VGTI was first made possible through a state-funded Oregon Opportunity Grant. The research has since been funded primarily through grants from the National Institutes of Health’s National Institute of Allergy and Infectious Disease, and the Bill & Melinda Gates Foundation, which has committed $46 million in grants to support Picker’s work at VGTI.

People Management for Principal Investigators, Mar. 10-11

Every principal investigator wants to build and maintain a lab that attracts and retains outstanding trainees and staff members. Juggling this endeavor with everything else the PI must do – writing papers, teaching, mentoring, gaining and maintaining funding, creating collaborative and productive relationships with other PIs – can be challenging at best. This 1.5-day course, led by Melanie Erskine and Rachel Dresbeck from the Office of the Senior Vice President for Research, will help you learn to manage people with a focus on the particular needs of running a lab or research group.

When: Friday, Mar.10, 9 a.m. to 5 p.m. and Saturday, Mar. 11, 9 a.m. to 12 p.m.
Location: School of Nursing, room 116
Register on Compass

In this course you will learn:

  • Strategies for approaching the role of “coach” in the lab – developing your leadership style
  • Recruitment and retention strategies – building (and maintaining) the best team for your lab
  • Steps to take when coaching doesn’t work – performance management in the lab
  • Resources that are available to you to support you and your lab staff

Enrollment is limited; there is no cost to participants.

NRSA application workshop: Technical components, Feb. 21

If you’re planning to apply for a pre- or post-doctoral NRSA fellowship from the NIH in the near future, we encourage you to attend this workshop to learn about essential, non-research elements of your fellowship application. Topics covered include elements needed for an InfoEd proposal, how to develop a budget, how to manage reference letters, biosketches and PMCID numbers, and elements of a great training plan.

This upcoming workshop is led by Johanna Colgrove, coordinator of the MD/PhD program, Gavin Hamilton, grants and contracts administrator with the Office of Proposal and Award Management, and Rachel Dresbeck, Ph.D., director of Research Development and Academic Communications.

NRSA Application Workshop
Tuesday, Feb. 21
10:30 a.m. to 12 p.m.
Biomedical Information Communication Center (BICC), room 124

Open to researchers and administrators. Registration now available on Compass.

Upcoming deadlines for Collins Medical Trust

The Collins Medical Trust is a local foundation that provides up to $30,000 three times a year to faculty and postdoctoral fellows. The purpose of these awards is to aid, further, promote and develop research related to the cause, cure, and treatment of human diseases. The Trust typically provides seed funding for projects that will be eligible for NIH or other substantial funding. Successful proposals will impact the heath of Oregonians, but also have the potential impact the research nationally. Young investigators applying should describe their relationship with a mentor to demonstrate they have guidance in their work.

OHSU can submit up to 15 applications for each deadline. Instead of accepting applications on a first-come, first-served basis, interested applicants will have a one-week window to submit a Notice of Intent Form to the OHSU Foundation. If multiple submissions are received from one department, the department  may be asked to determine which application will move forward. Preference will be given to applicants that have not recently received Collins Medical Trust funding. Resubmissions are not encouraged.

Upcoming deadlines:

The Notice of Intent window is February 3-10. Please note that NoIs will only be accepted during this window. If you have already submitted an NoI, you will need to resubmit during the submission window. Full applications are due to OPAM by April 10 and must be sent to the OHSUF by April 21. The Collins Medical Trust deadline is May 1.

If you are interested in submitting an application for an upcoming deadline, the first step in the process is to fill out the OHSU Foundation Notice of Intent Form, which can be found on the Collins Medical Trust O2 page along with policies and procedures and frequently asked questions.

 

Welcome to the Research News Blog

Welcome to the Research News Blog

OHSU Research News is your portal to information about all things research at Oregon Health & Science University. Visit often for updates on events, discoveries, and important funding information.

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