OHSU forum: Data science and biomedical research, Apr. 20

The OHSU community is invited to attend a forum with Philip Bourne, Ph.D., associate director for data science at the National Institutes of Health, presenting on data science and biomedical research.

Forum and Q&A
Wednesday, Apr. 20
12 p.m.
Mackenzie Hall 1162

The associate director and his office provide input to the overall NIH vision and actions undertaken by each of the 27 Institutes and Centers in support of biomedical research as a digital enterprise. They are currently focused on five programmatic themes and welcome community input to shape the efforts in a time of profound change in how biomedical research is undertaken. Prior to his position at NIH , Bourne was the associate vice chancellor for innovation and industrial alliances and a professor in the Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego. .

Bourne will make a few introductory remarks followed by a Q&A session.

NIGMS seeks input on team science research

The National Institute of General Medical Sciences is examining the benefits and challenges of team science and considering how best to support this mode of scientific research. In doing so, NIGMS is seeking input from the biomedical research community to assist in considering the needs and opportunities in team science at the multi-investigator, institutional, regional and national levels. For the purposes of this Request for Information (RFI), team science and team-based research are defined as research that involves multiple investigators to answer questions that cannot be answered either by a single investigator and his/her lab or by a group of closely collaborative investigators supported on a multi-PI R01 grant.

Input is sought on the following:

  • Interest in team science – Comments may include the relative importance of team science in your field and sharing your own experiences.
  • Management and advisory structures in team science – Suggest types of management structures within a project that would enable an effective team science program (e.g. leadership models, use of external review groups, etc.) as well as challenges and solutions for issues around management.
  • Team composition – May include comments on recruiting team members, training, the value of diversity in team science and the challenges of recognizing individual efforts on team science research.
  • Resources and infrastructure – Comments on technical and administrative cores, both existing and those that would need to be established to facilitate team science.
  • Assessment of team science – Factors to be considered in the peer review of team science-based grant applications as well as appropriate quantitative and qualitative measures of success and impact.
  • Comments on past or current NIGMS team-based programs and funding mechanisms
  • Other issues

Responses will be accepted through June 17, 2016. All comments must be submitted via email as text or as an attached electronic document. Microsoft Word documents are preferred. Responses should be addressed to TeamScience@mail.nih.gov.

This is a great way to help shape a new program in its formative stages. Please make your voices heard!

Study confirms mitochondrial mutations increase with age, impact stem cell treatments

A team led by Shoukhrat Mitalipov, Ph.D., director of the Center for Embryonic Cell and Gene Therapy at OHSU, has confirmed that mutations in mitochondrial DNA accumulate with age and can limit cells’ ability to create energy and function properly. The study examined induced pluripotent stem (iPS) cells derived from patients’ skin or blood cells and identified faulty DNA, with each cell having potentially different types and percentages of mutations. These defects could undermine the iPS cells’ ability to repair damaged tissue or organs and impair their therapeutic value.  © Copyright 2014 Corbis Corporation

The study published Apr. 14, in the journal Cell Stem Cell, examined blood and skin samples of patients ranging from 24 to 72 and in various states of health. Because these samples contained millions of cells, most mitochondrial mutations remained hidden with initial testing. However, when the researchers sequenced the iPS cell lines – expanded clones of individual cells- they found higher numbers of mutations, particularly in cells from patients older than 60.

“Pathogenic mutations in our mitochondrial DNA have long been thought to be a driving force in aging and age-related diseases, though clear evidence was missing. Now with that evidence at hand, we know that we must screen stem cells for mutations or collect them at younger age to ensure their mitochondrial genes are healthy,” said Mitalipov. “This foundational knowledge of how cells are damaged in the natural process of aging may help to illuminate the role of mutated mitochondria in degenerative disease.”

The study, “Age-Related Accumulation of Mitochondrial DNA mutations in Adult-Derived Human iPSCs,” was supported by the Fondation Leducq, OHSU institutional funds and Mayo Clinic Center for Regenerative Medicine and the Cincinnati Children’s Hospital Research Foundation.

Further details and a list of coauthors can be found in the full press release.

Volunteer as a presentation judge at Research Week!

ResearchWeekArt2106 FNL RGBResearch Week 2016 is fast approaching and we need your help! We are looking for 51 faculty, postdocs, and research staff to serve as judges for students and postdocs who are presenting talks and posters during Research Week, May 2-6. For each session for which you sign up to judge, you’ll be asked to evaluate a maximum of four student presentations (either oral or poster). Visit the sign-up page for a full listing of session dates, times, and research topics that need coverage. To sign up, check the box for the session you’re interested in and click “submit”–once you get into the tool, you’ll be able to see full details. You can also view the session schedule to see which research presentations fit your expertise.

This is a great opportunity to provide valuable feedback to students and postdocs, and to learn more about the wide-ranging, innovative research taking place here at OHSU.

We kindly ask that you register as soon as possible so we can fill any gaps before the main event. Thank you for contributing to a successful Research Week 2016!

Researchers demonstrate the impact of obesity on emergency contraception

Edelman_Alison_15OHSU clinical researchers Alison Edelman, M.D., M.P.H., and Jeffrey Jensen, M.D., M.P.H., published a study that examined why emergency contraception isn’t as effective in obese women, and how to potentially increase its effectiveness in this population. The findings, published March 19 in the journal Contraception, show how obesity adversely impacts circulating levels of emergency contraception, and that doubling the dose appears to correct obesity-related interference in the drug’s efficacy.Jensen-Jeffrey_12

Roughly half of all pregnancies in the U.S. are unintended. Single-dose emergency contraception (EC), commonly referred to as “the morning after pill,” has the potential to decrease the risk of pregnancy following unprotected sex by nearly 90%. The most commonly used EC is the progestin hormone levonorgestrel (LNG); now available over the counter to both adults and adolescents, its use is increasing. Unfortunately, the LNG-based method appears to be significantly less effective in obese women, failing 4 times as often as in non-obese women. The exact mechanism for this phenomenon remains unknown and no prior studies have compared this EC’s effectiveness between obese and women of normal weight.

In their paper, “Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: Single and double dosing,” the authors provide evidence of how obesity interferes with the pharmacokinetics (how the body responds to a drug’s movement into and out of the body) of LNG. Women enrolled in the study were given both a single and double dose of LNG, then free (pharmacologically active) and total LNG levels were measured in blood samples at various time intervals after administration. What the researchers found was the levels were significantly lower in obese women who had received a single dose vs. non-obese women, but LNG levels increased significantly with a double dose of the drug, nearly equal to the levels observed in normal BMI subjects receiving a single dose.

While the team was unable to determine a clear mechanism for obesity’s significant impact on LNG due to a limited sample, it does appear that binding proteins play a key role. Levels of sex hormone binding globulin (SHBG) are lower in the obese, and since LNG is bound to SHBG, unpredictable clearance of the hormone can occur. They conclude that doubling the LNG dose may be an effective strategy to improve its efficacy in obese women.

This work was made possible by the support of the Medical Research Foundation of Oregon (Grant 1501), the National Institutes of Health support of the OHSU Oregon Clinical & Translational Research Institute (NIH NCRR 1 UL1 RR024120), as well as the Oregon National Primate Reserach Center core grant (OD011092). Co-authors on this study: Ganesh Cherala, Ph.D., Steven Blue, and David Erickson, Ph.D.

Volunteers needed for Research Week 2016!

ResearchWeekArt2106 FNL RGBResearch Week 2016 is less than a month away, and we need your help! Each year, volunteers play a critical role in in making Research Week a success. Anyone at OHSU can volunteer. It’s a great opportunity to meet people from other areas and gain an understanding of the scope and quality of the research conducted every day at OHSU. There are a number of ways volunteers can help:

Check-in Desk
As a Check-in Desk volunteer, you are tasked with greeting attendees and checking in presenters.

Poster Wrangler
It’s the Poster Wrangler’s job to see that posters are put up in the right locations.

3MT Ballot Collector
Help collect the audience ballots for the “People’s Choice Award” at the end of the Three Minute Thesis competition on Wednesday, May 4.

Moderator/Backup Moderator
Every oral presentation session will be assigned two volunteers: One Moderator and one Backup Moderator. Moderators are needed to ensure that the pace of the oral presentation sessions are maintained, keeping presenters to their 10-minute time limit.

Go to the Research Week 2016 volunteer website to see what shifts are available and to sign up to be a volunteer. All volunteers will get this year’s super stylish Research Week T-shirt in appreciation of your efforts. Remember, you can choose as many shifts as you’d like!

Intel’s Eric Dishman named Director of Precision Medicine Initiative Cohort Program

20160411-eric-dishman-pmi-1NIH has announced the selection of Eric Dishman to head up the Precision Medicine Initiative (PMI) Cohort Program. He will oversee the PMI landmark research study of roughly one million volunteers, designed to provide new insights into human disease and identify how precision medicine can improve health outcomes.

One of Oregon’s top executives, Dishman most recently served as VP and Intel Fellow of Intel Corporation’s Health & Life Sciences Group based here in Portland. For over 15 years, he oversaw Intel’s global strategy, research, platform development, and policy in key areas like health IT, genomics, consumer wellness, and care coordination technologies. A recognized global leader in healthcare innovation, Dishman is known for pioneering innovation techniques that incorporate anthropology, ethnography, and other social science methods into the design and development of new technologies. He has served as a key member of the PMI working group, and precision medicine – the study of individual variability in genes, environment, and lifestyle to produce targeted treatments – has been a key focus of Dishman’s work at Intel. He will now oversee the study he helped design.

On a personal level, Dishman brings the patient experience with him. Diagnosed with kidney cancer at a very young age, he has been battling the disease for 23 years and only recently became cancer free due to early access to a precision medicine treatment plan. According to NIH Director Francis Collins, “These experiences and perspectives are crucial to the PMI Cohort Program, which, in addition to advancing health and improving treatments for disease, will also pioneer a new model of research in which participants will be partners in the research process and actively engaged and informed. As Eric recently told me, ‘I have been put on this earth — and survived a seemingly impossible cancer journey—to help bring precision medicine to everyone.'”

 

Watch seasoned reviewers discuss NIH proposals as if you were there

Charles RaffertyThe Mock NIH Study Section, led by Charles Rafferty, Ph.D., will review both an NIH K career development and an R01 application with a panel of OHSU faculty acting as reviewers. This part of the Research Week 2016 event will demonstrate how grants are evaluated and discussed through the NIH peer review process – and provide insight into improving your own grantsmanship. In addition, we need your participation! The audience will be asked to score the applications too.

Mock Study Section
Tuesday, May 3
12 to 1:30 p.m.
OHSU Auditorium

Grants to review will be posted by April 18th. Before then, prepare ahead by reviewing the critique templates, review guidance and NIH scoring tables provided to NIH reviewers.

Who’s who at OHSU: Matt Whorton, Ph.D.

Matt Whorton, Ph.D.

Matt Whorton, Ph.D.

Vollum Institute researcher Matt Whorton, Ph.D. was recently presented with an American Asthma Foundation (AAF) Scholar Award for his work on the structure and function of adenylyl cyclase. This highly competitive award supports basic research with potential applications to the study of asthma. We recently sat down with Whorton to discuss his research and learn more about his AAF project.

The AAF Scholar Award is a unique funding opportunity for basic scientists. Can you tell us about it?

Yes, the Foundation tries to attract people not already in the field by inviting applications that are innovative and that approach the disease from a new angle.

What research are you involved in and how does it pertain to the field of asthma?

I focus on protein mechanisms – how proteins work and how they’re regulated.  I’m particularly interested in proteins embedded in cell membranes that are involved in transporting molecules or ions across these membranes.

The primary focus of my AAF award will be to examine a membrane protein called adenylyl cyclase. I’ve known about this protein for a while from having worked with a class of receptors called G-protein coupled receptors when I was in graduate school. These receptors are widespread throughout the body and expressed in cell membranes. They respond to ligands and drugs outside the cell and pass the information inside the cell. One thing these receptors do is activate other proteins, and one of the main targets is adenylyl cyclase. This activation then leads to the creation of a molecule, cyclic AMP, which can diffuse into the cell and does a number of things depending on the cell type and tissue.

Structure of a potassium channel, GIRK, that Whorton also studies

Structure of a potassium channel, GIRK, that Whorton also studies

These systems are all over the body but are particularly important in the lungs, because when cyclic AMP is produced, it causes the airway muscles to relax, making them wider and allowing for easier breathing. People with asthma have constricted airways, either because they have too much mucus or because these systems are deficient and the muscles are always contracted. The current drug treatment for asthma is the use of beta agonists, which activate these receptors to turn on the production of cyclic AMP.  But up until now, people haven’t really looked at adenylyl cyclase from a mechanistic point of view in terms of how the whole protein works and how it’s regulated, because it happens to be regulated by many different types of inputs and therefore poorly understood. So, my initial goal is to see at an atomic level what the protein looks like and then how its conformation is regulated by other proteins in the cell to either enhance or inhibit the creation of cyclic AMP. Since cyclic AMP is so important in controlling smooth muscle tone and is central to how asthma is treated, understanding how it’s regulated has the potential to lead to new therapeutics for across the asthma spectrum as well as other lung diseases such as Chronic Obstructive Pulmonary Disease.

New NIH application guide, instructions now available

As previously reported, changes to NIH policies and guidelines are being implemented in several phases this fiscal year and into FY 2017, with some confusion surrounding how best to incorporate them. On Mar. 28, the NIH finally released its updated application guide and supplemental instructions for use with grant applications due on or after May 25, 2016.

Key changes include but are not limited to:

  • New How to Apply – Application Guide webpage
  • New formatting of the general application instructions including interactive HTML and PDF versions as well as an integrated format for all types of grant mechanisms
  • Grant mechanism-specific filtered views of the application instructions
  • Inclusion of a chart that shows which application instructions to follow for each activity code
  • Reduction in duplicative information throughout the instructions

In addition, updates to form instructions are listed here.

Hopefully these updates will make it easier for you to find the information you need. But, if you’re still confused or would like to provide any feedback on the new guidelines and instructions, NIH wants to hear from you. You can also direct your questions to Research Funding and Development Services at funding@ohsu.edu.

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Welcome to the Research News Blog

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