Parkinson’s grants awarded to three OHSU researchers

The American Parkinson Disease Association announced today, Aug. 3, that it has awarded $1.6 million toward research for the 2016-2017 funding cycle. Three OHSU researchers are among the recipients of this year’s awards.

unniVivek Unni, M.D., Ph.D., assistant professor of neurology in the Parkinson Center of Oregon and Jungers Center for Neurosciences Research at OHSU, is the recipient of the prestigious George C. Cotzias Fellowship, named in honor of the scientist who helped develop Levodopa as a treatment for Parkinson’s disease. The fellowship award will support Unni’s research using new imaging approaches to examine the molecular mechanisms of Lewy body pathology-associated death in mouse models of Parkinson’s disease. Specifically, Unni’s lab is working to distinguish between protective and toxic alpha-synuclein protein aggregates which may lead to new treatments to slow Parkinson’s disease progression.

martinIan Martin, Ph.D., assistant professor of neurology in the Jungers Center for Neurosciences Research with membership in the Parkinson Center of Oregon, received one of seven of the association’s research grants. The funding will support his research defining key pathogenic mechanisms underlying neurodegeneration in Parkinson’s disease.

Vinita-Chittoor-120Vinita Ganesh Chittoor, Ph.D., a postdoctoral researcher in the Martin lab, was one of only three Post-Doctoral Fellowship Award recipients. Chittoor works on evaluating the influence of diet on LRRK2-mediated toxicity in Parkinson’s disease. (Mutations in LRRK2, an enzyme encoded by the PARK8 gene, are a proven cause of PD.)

The grants are awarded through a competitive application process and reviewed by American Parkinson Disease Association’s scientific advisory board. “The objective…is to invest in the best science,” said David G. Standaert, M.D., Ph.D., John N. Whitaker Professor, chair of neurology, and director, Division of Movement Disorders, University of Alabama at Birmingham, and chairman, scientific advisory board. “As we evaluate these proposals, we focus on funding researchers who are at the start of their Parkinson’s research career and seek to attract the best and brightest minds to work on this important problem. Our aim is to accelerate research and support translational ideas that have the potential to truly improve the quality of life for persons living with PD.”

Grant applications: A quick guide to rigor and reproducibility

Many of you still have questions about how to address the new NIH requirements on rigor and reproducibility in your grant applications. Last week, NIH published a new one-page resource to walk you through the four key areas of scientific rigor: Scientific Premise, Scientific Rigor (Design), Biological Variables, and Authentication. The guide can be downloaded as a PDF. Additional resources supplying more in-depth information can be found on the NIH grants policy website and the NIH website.

Click the image to enlarge and download.

RigorandReproducibilityChart508 (1)

University Shared Resources pilot award applications due Oct. 7

The OHSU University Shared Resources (USR) program and the Office of the Senior Vice President for Research are soliciting grant applications for the second round of the USR Core Pilot Awards program. These awards support OHSU faculty and USR cores by providing pilot funding for principal investigators, especially to support generation of data for new grant applications, as well as to support core development. The program will provide two types of funding this round:

  • Faculty pilot funding: Up to roughly $5,000 for awards utilizing available core resources and services. Applicants must be OHSU faculty members. Previous awardees are eligible to apply with a new project, but new applicants may be given priority.
  • Core innovation funding: Up to roughly $10,000. Applicants must collaborate with one or more USR core director in developing new workflows, assays, or technologies that will benefit the core program.

Requirements:

  • PIs must contact USR core director(s) to assess feasibility and discuss budgets prior to applying. A single award may be used to support a project that involves more than one USR core.
  • All funds must be spent in a USR core. No FTE, supplies, or other expenses outside the USR will be allowed. Funds are only to be used for data generation or services with the cores, including consultation time in the core and other technical services.
  • Funds must be spent in FY2017.
  • Applicants must cite this support and core contributions in relevant publications.
  • Applicants must acknowledge specific USR cores in relevant publications.

Applications must be filled out online through OHSU’s Competitive Application Portal (CAP). Full instructions are provided on CAP and can also be found here.

Please note: Applicants must consult with the director of the designated core prior to application submission. An email from the core director(s) acknowledging a consultation must be received by USR Program Director Andy Chitty before applications can be moved forward for review. Applications are due Oct. 7, 2016, and awards will be announced in late fall.

Learn more here.

Peer review scoring: Why some grant applications are more likely to be funded than others

Anyone who’s worked hard on an NIH grant application that didn’t get funded wonders what they could have done differently to improve their chances of success. A recent analysis on peer review scoring by the NIH Office of Extramural Research (OER) provides insight into how to improve overall impact scores and the likelihood of getting funded.

In a July 22 Open Mike blog post, OER Director Mike Lauer, describes NIH’s quest to better understand the “stories behind [NIH] metrics” in order to develop and implement data-driven policy. To that end, a group of authors from OER analyzed over 123,000 competing R01 applications, correlating individual component peer review scores – approach, significance, innovation, investigator(s), and environment – with overall impact score and funding outcome. Their findings, published last month in PLOS ONE, showed that an applicant’s approach score, and to a lesser extent the significance score, were the most important predictors of whether an R01 application will score highly on overall impact and whether it’s funded.

R01 graph

From: “How Criterion Scores Predict the Overall Impact Score and Funding Outcomes for National Institute of Health Peer-Reviewed Applications”

 

Though these results merely confirm what’s been reported in previous studies, it’s helpful to know that the description of the experimental approach continues to be the most important predictor of funding, followed by the significance of the study, according to Lauer. Reviewing NIH’s peer review guidance that addresses approach and significance may be helpful when putting your application together.

The analysis also showed that overall impact scores and funding rates varied widely according to different application characteristics. For example, new applications had relatively higher overall impact scores than renewal applications (37.1 vs. 30.9) but had lower funding rates (14.2 percent vs. 30.1 percent). Resubmissions (A1s) had a more favorable average overall impact score and funding rate than initial submissions (A0s). Additional data on outcomes by race and gender were provided. Lauer will address related additional data in an upcoming Open Mike post, so stay tuned.

 

OHSU researchers open new field in cellular metabolism

A team of researchers from OHSU has developed a new biosensor for a molecule critical for healthy cellular function, nicotinamide adenine dinucleotide (NAD+). NAD+ is a coenzyme found in every cell, helping  to drive glucose metabolism. It is known to decline with advancing age, and this decline is thought to play a role in age-related diseases such as cancer, cardiovascular disease, and neurodegeneration. While NAD+ was discovered about 100 years ago, we still don’t know much about how it is regulated in cells or tissues. Most cellular NAD+ is found within mitochondria, but other pools are found in the cytoplasm and nucleus, where they regulate enzymes that serve many different functions. To date, no one has been able to determine how much free NAD+ was available in specific cellular compartments, whether these levels were appropriate to regulate the various NAD+-related enzymes, or even how NAD+ gets into mitochondria. Now, OHSU authors Xiaolu A. Cambronne, Melissa L. Stewart, DongHo Kim, Amber M. Jones-Brunette, Rory K. Morgan, David L. Farrens, Michael S. Cohen, and Richard H. Goodman describe a new fluorescent biosensor that allows direct measurement of free NAD+ concentrations in live cells—in essence, opening an entirely new field. Their work, “Biosensor reveals multiple sources for mitochondrial NAD+,” was published in Science on June 17.

The biosensor is genetically encoded, utilizing a form of fluorescent protein and a bipartite NAD+-binding domain. Using this tool, Cambronne and colleagues found that NAD+ is distinctly regulated in different cell types and subcellular pools and that its local concentrations can regulate resident enzymes. This work builds on long-standing work—including earlier work carried out at the Vollum. It confirms previous estimates of NAD+ concentrations that were based on fluorescence lifetime measurements, details how the different cellular compartments of NAD+ relate to one another, and suggests how NAD+ gets into the mitochondria, where it can participate in metabolic processes. This discovery is important because it lays the groundwork for determining exactly how NAD+ contributes to health and disease. For example, the biosensor could provide insight into some forms of neurodegeneration, such as those caused by axon injury.

Cambronne, Stewart, Kim, and Goodman are from the Vollum Institute; Jones-Brunette and Farrens are from the Department of Biochemistry and Molecular Biology in the School of Medicine; and Morgan and Cohen are from the Department of Physiology and Pharmacology in the School of Medicine.

Two trees to be removed from Research Courtyard

UPDATE Tuesday, Aug. 2: The two trees were removed on Saturday, July 30.

Within the coming weeks, two tall conifer trees in the Research Courtyard between Mac Hall Cafe and the new Center for Radiochemistry Research will be removed due to an imminent safety hazard. During the course of CRR construction and courtyard renovations, crews discovered the conifers in the southwest corner had inadequate root systems to support their height, posing a toppling risk. The trees could be removed by OHSU’s arborist as soon as Saturday, July 30. The removal will take place over a weekend to avoid disturbing campus activities.

New course requirements for Responsible Conduct of Research

If you’re a researcher at OHSU, you know that the university and funders such as NIH require you to keep up to date in your knowledge of the responsible conduct of research. In the past, we used our in-house Big Brain tool and in-house courses. But as of May 1, 2016, RCR education has moved to the University of Miami’s CITI Program. The CITI Program meets NIH standards and is the standard for the majority of academic institutions in the U.S. and the Veteran’s Administration.

Depending on your work, you will need to take at least one of the following modules.

  • Responsible Conduct of Research (RCR). Previously called “RCR for All” in Big Brain. This course is required for anyone involved in research at OHSU.
  • Animal Care and Use (ACU): Working with the IACUC. Previously called “RCR involving Animal Subjects” in Big Brain. This course must be completed by researchers who use animals.
  • Human Subjects Research (HSR): Human Researchers. Previously called “RCR involving Human Subjects” in Big Brain. This course must be completed by researchers conducting research with human subjects.
  • Biosafety/Biosecurity: Working with rDNA/Infectious Agents/Toxins. Previously called “RCR involving rDNA, Synthetic Nucleic Acid Molecules and Infectious Agents/ Biological Toxins” in Big Brain. This course must be competed if you work with recombinant DNA, synthetic nucleic acid molecules in cells, organisms or viruses, infectious agents, or biologically derived toxins.
  • Good Clinical Practices (GCP). Previously called “RCR for FDA Regulated Products” in Big Brain. This course must be completed by investigators or staff on a clinical trial of an FDA-regulated product (drug or device).

Changes for all researchers

In the past, you may have taken one class and then only needed to take a booster every year. You will now be required to renew your CITI training every three years in lieu of taking a research-specific booster training. Refresher training is important because the regulatory environment is always changing—and it’s the standard at many institutions, such as UCSF, University of Arizona, Case Western among many others.

Other changes: the CITI modules take longer than Big Brain modules. Expect to devote at least an hour to each one.

First time user of CITI?

Please follow these instructions for accessing OHSU’s CITI account.

Advantages of CITI

Because CITI is so well adopted across the U.S., it allows a high degree of reciprocity for multicenter research as well as for faculty conducting research at the VA and faculty transferring from other universities.  Be sure to follow the instructions for linking an already established CITI account to get credit for modules already completed!

Additionally, using the CITI program allows OHSU to take advantage of regularly updated content and new course options.

When do I have to complete CITI training?

If you completed the RCR course in Big Brain before May 2014:

  • You will be notified beginning July 2016 that you must take the required CITI course modules
  • You must complete the CITI course before May 31, 2017 to be considered compliant for grant funding, eIRB applications, etc.

If you completed the RCR course in Big Brain after May 2014:

  • You will be notified beginning  July 2017
  • The course certification expires beginning May 31, 2018 on a rolling 3-year basis, dependent on when you last completed the Big Brain course. For example, if you completed your course between June 1, 2014 and May 31, 2015, you will not be due until May 31, 2018. After this, your certification will expire every 3 years.

Log into Compass to find your due date. You will also receive periodic reminders from OHSU Research Integrity about the deadline.

If you no longer need to complete a course that has been assigned to you, please reply to integrity@ohsu.edu. Let them know which course specifically no longer applies to you and why; they will remove the course from your transcript and stop sending you reminders.

Visit the website for more information on RCR education and contact integrity@ohsu.edu with any questions.

Who’s new at OHSU? Raymond Bergan, M.D.

Raymond Bergan, M.D., is an internationally regarded cancer researcher who joined OHSU as head of hematology and medical oncology in the School of Medicine and as associate director of medical oncology for the OHSU Knight Cancer Institute. He is also a practicing clinician who sees patients at OHSU and the Veterans Administration Portland Health Care System.Bergan Raymond_15

What brought you to OHSU?
My decision to leave Northwestern University and come to OHSU was two-fold. The opportunity to lead the Hematology & Medical Oncology Division was a big draw but I came in large part because of what OHSU is doing for the field. I’m a medical oncologist and have been in drug discovery and therapeutics – that’s my area of focus. I had been at Northwestern for a long time and got to a point where I asked myself “What do I want to do with the rest of my career?” A career I’ve spent helping patients, developing better therapeutics for patients, and I could see where the field was going – toward precision medicine and personalized therapy. So I thought “Do I want to stay [at Northwestern] and wait for the new guidelines to come out or do I want to go and help shape and define those guidelines? I wanted to help move that science forward and felt this was the right place because of what OHSU was doing for cancer, providing a visionary way forward as objectively measured by the Knight Challenge.  It’s not about the money per se but about the tools and capabilities it affords and how OHSU is using the money that is significant.

What is the focus of your research?
I came to this division because I thought it had huge potential for further advancing therapeutics. What our group does scientifically is to understand why cancer cells move and therapeutically inhibiting that process. The example I often use is, say a woman discovers a lump in her breast and it turns out to be breast cancer. If it’s just that lump, it’s easy to treat and cure using a local therapy such as surgery or radiation or sometimes chemotherapy; if that cancer hasn’t moved, the woman is cured. If, however, that cancer has moved throughout her body, we can treat it but we can’t cure it. The analogy for breast is true for most cancers. The leading cause of death from cancer is metastatic cancer. So how does that cancer go from the original point and move throughout the body? What kills patients is that process of cell movement, so if you can block that process, you can cure people.

There are many things that are attractive about focusing on motility as a therapeutic target. Until recently, no one had actually been able to do it. But we have. We were the first group to successfully therapeutically target pathways in humans that act to inhibit that process. To clarify, we’ve inhibited a pathway inside cells that’s an important driver of that process. We have not yet shown that we can stop cancer cells from moving in patients and thus have not yet demonstrated benefit to patients. So this is the focus of our laboratory. We’re starting out with prostate cancer, but the research isn’t necessarily limited to that. The overall aim is to discover what regulates and controls cell movement or transformation to a metastatic phenotype and then what part of that process can be therapeutically targeted. We’ve taken agents from bench into clinic through phase II trials, and now we’re putting a lot of effort into discovery of a novel class of agents and moving that forward. This is what’s nearest and dearest to my heart in terms of what our group is working on.

Bergan labLinked to that, I’m also involved in early phase clinical trials. I have a long history in the field of chemo-prevention.  At Northwestern, I put together–and served as PI for over a decade–one of only five National Cancer Institute-funded early phase chemoprevention consortia groups. I built the group to 19 institutions, including two in China, and ran a variety of clinical trials. Early phase trials are what you would consider “go – no go” trials for larger, expensive and potentially risky trials. If you have a promising agent and you’ve run it through a Phase I trial and are confident the drug isn’t toxic, you go to the next phase to see if it does anything of use. If it’s an effective chemoprevention agent acting as expected, you would run a trial in humans looking at target cells in the target tissue in the body to see if you get a response.  The outcomes of these early stage trials have molecular endpoints that allow you to say, yes, this is worth further investigation because we know that a certain dose given to a targeted cohort exerts the pharmacologic effect we want in the exact organ we want to target. Tamoxifen is an example of a very successful chemoprevention drug that blocks the actions of estrogen, which is effective against tumors that require estrogen to grow.

But say you developed a drug and in early trials, you didn’t get the response you’d anticipated. We wouldn’t just throw the drug out. We would look at it closely and ask “is it a bad drug? Did we not administer the correct dose?” We might be able to rescue the drug if we find it was a case of bad formulation or we didn’t administer the drug properly. So that’s the purpose of this consortium – to run these types of trials which are very complex and require experts in a particular cancer type or methodology, etc. A single research group or institution can’t cover all those bases which is why a consortium is needed. When I came here I had to give up my leadership of the group, which was probably the hardest thing I’ve ever had to do professionally. Ultimately, the award is made to the institution, so it stayed at Northwestern.  But I’m still heavily involved. When I came here, I made OHSU a site and I’m now chair of the Eastern Cooperative Oncology Group Prevention Committee.

I’m passionately committed to this work. I think the way we’re going to have the biggest impact on cancer is in early detection and early intervention.

What do you do when you’re not at work?
I love Portland. I knew nothing about it prior to coming here other than having read a few things. There’s so much about it that reminds me of home. I grew up in a rural area of upstate New York in a small town, and I spent a lot of time in the woods when I was young.  Here I walk to work and when I’m done working, I’m running on a wooded trail right outside my door. I’m happy anywhere and very much liked living in Chicago.  However, Chicago is a large city, and it would take you a long time to get out of it. Here, you have a real city with a downtown that’s vibrant, but you can get out of town in half an hour. I’m also currently learning Chinese, I read a lot of biographies, and I have three wonderful kids that I love spending time with.

 

Postdoctoral fellowships from the Human Frontier Science Program

Human-Frontier-Science-Program1

Attention Postdocs!

The Human Frontier Science Program encourages postdoctoral scientists to broaden their research skills by moving into new areas of study while working in a new country. The program provides awardees with approximately $50,000 per year for three years (with additional travel and child allowances) and invites applications for two international mechanisms that offer postdoctoral fellowships for basic research training:

Long-Term Fellowships – For applicants with a Ph.D. in a biological discipline to embark on a new project in a different field of the life sciences. Preference is given to applicants who propose an original study in biology that marks a departure from their previous Ph.D. or postdoctoral work so as to learn new methods or change discipline.

Cross-Disciplinary Fellowships – For applicants with a Ph.D. from outside the life sciences (e.g. in physics, chemistry, mathematics, engineering or computer sciences) who have had limited exposure to biology during their previous training. Applicants should propose a significant departure from their past research (e.g. changing from material science or physics to cell biology, from chemistry to molecular biology, or from computer science to neuroscience).

Registration deadline: August 11, 2016
Application deadline: August 25, 2016

Fellows must begin their fellowship between April 1, 2017 and January 1, 2018. To be eligible, the applicant must hold a research doctorate or a doctoral-level degree comparable to a Ph.D. with equivalent experience in basic research and the degree must have been conferred in the three years prior to the submission deadline or by December 31, 2017. Applicants must have at least one lead author paper either accepted for publication, in press or published, in an English peer-reviewed international journal. Applicants who have spent 12 or more months in their proposed host country or with their proposed supervisor are ineligible.

Learn more here.

West Coast Nature Awards for Mentoring in Science: nominations due Aug. 8

mentor-bigThe guidance and support mentors provide in labs is too often overlooked. In response, in 2005 Nature created an award aimed at recognizing outstanding scientific mentorship which recognizes different regions of the world each year. This year’s Nature Awards for Mentoring in Science will go to exceptional mentors from the US West Coast states – Washington, Oregon, and California – and nominations are now open.

Two prizes of $10,000 will be awarded, one for a mid-career mentor and one for life-time achievement in mentoring.

Eligibility: Nominees may be working in any discipline within the natural sciences and should be residents of one of the West Coast states. Nominees may be nominated by colleagues and ex-colleagues or nominate themselves. Nomination packages must include independent testimonials by five researchers mentored by the nominee, not all over the same period.

The closing date for nominations is Monday, Aug. 8, 2016. Further information about eligibility and how to submit a nomination is available here. You can find further background information on the program including past awardees here and here.

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