OCTRI seeks investigators with clinical trials to pilot recruitment using MyChart

Click the image to enlarge and download the flier.

Click the image to enlarge and download the flier.

It’s often a challenge to recruit the right subjects for clinical trials–and the right number of subjects.  An approach adopted by other academic health centers is to use the patient portal MyChart. Using MyChart has been shown to increase rates of study enrollment by up to three times and do so at one-fifth the cost, compared with mailings and phone calls to subjects. Currently, more than 130,000 MyChart accounts are active through OHSU.

To determine the feasibility of using MyChart as a recruitment tool here, the Oregon Clinical and Translational Research Institute is conducting a study of its own. OCTRI is looking for two or three clinical studies that would be suitable as pilot projects for MyChart-enabled recruitment. A clinical informatics team will work with each researcher to glean an understanding of how MyChart can be used to increase enrollment.

Eligible studies should be recruiting before Sept. 2, 2015, and meet other criteria outlined in the the flier embedded in this post. Questions? Contact Tim Burdick, chief clinical research informatics officer.

OHSU researchers identify structural changes in the cannabinoid receptor, yielding new insights into alternate GPCR signaling states

Jon Fay and David Farrens

Jon Fay and David Farrens

If you’re a vertebrate animal, you should be interested in new findings from the Farrens lab. All vertebrates use G protein-coupled receptors (GPCRs) to detect a variety of different stimuli. Upon binding their target molecules, these membrane proteins undergo structural changes that induce internal signal transduction cascades and alter cellular responses. Because GPCRs are involved in so many signaling systems and diseases, they are a common drug target in pharmacology.

Recently, two exciting new areas of GPCR research have emerged. The first revolves around the discovery that GPCR activity can be modulated by allosteric ligands. These allosteric drugs bind at sites completely different from where traditional GPCR drugs are known to bind. The second new area involves the discovery that GPCRs are surprisingly flexible and often play more than one role in the cell. For example, sometimes different drugs can bind at the same spot on a GPCR, yet activate different signaling pathways. The latter process, called “biased signaling,” can occur for drugs binding in the traditional “pocket” in the receptor, as well as for allosteric ligands. Understanding how both these phenomena occur is of great therapeutic interest. New allosteric ligands that can preferentially induce biased signaling for one pathway versus another hold promise as a powerful way to complement the effect of existing pharmaceuticals, further dial in GPCR responses, and optimize the beneficial aspects of existing drugs while minimizing negative side-effects.

Precisely how allosteric ligands could induce biased signaling behavior is not known. However, a new paper by Jonathan Fay, Ph.D., and David Farrens, Ph.D., has begun to address this question by looking at the structural biology of the receptor.

G protein-coupled receptors (GPCRs) are intrinsically dynamic proteins that serve as conduits for disseminating information across the cell membrane.  Here, a fluorescent probe bimane (green) was attached to a the human Cannabinoid receptor (blue) to identify conformational fluctuations  that occur in the receptor (purple haze) upon binding small molecule ligands that bind to the traditional binding site (aqua) as well as allosterically (white).

G protein-coupled receptors are intrinsically dynamic proteins that serve as conduits for disseminating information across the cell membrane. Here, a fluorescent probe, bimane (green), was attached to the human cannabinoid receptor (blue) to identify conformational fluctuations that occur in the receptor (purple haze) upon binding small molecule ligands that bind to the traditional binding site (aqua) as well as allosterically (white).

Their study, “Structural dynamics and energetics underlying allosteric inactivation of the cannabinoid receptor CB1,” published in the July 7, edition of PNAS, discovered that a new structure is induced in the marijuana receptor (called CB1) by an unusual allosteric ligand, Org 27569. They found that while Org 27569 causes CB1 to bind more activating drugs (cannabinoid agonists), at the same time it inhibits the receptors’ ability to activate G-protein signaling.   Intriguingly, their results indicate that the binding of Org 27569 induces a new structure in the CB1 receptor, one that is biased towards other signaling pathways. Based on their findings, they proposed that this new structural state may be something that can universally occur in other GPCRs, thus affecting their signaling pathways as well.

These findings about the cannabinoid receptor are especially interesting, as they indicate that this receptor—which is common across multiple species—can be affected by multiple drugs binding at different sites. Together, these results indicate the potential for developing new pharmaceuticals that can complement, not compete with, cannabinoids, thus channeling signaling in directions that would be more beneficial for patients and cannabinoid enthusiasts.

This study was funded by NIH Training Grant T32 DA007267 (to J.F.F.) and NIH Grants R01 EY015436 and S10 RR025684 (to D.L.F.). David Farrens is an associate professor and Jonathan Fay is a senior post-doc in the School of Medicine Department of Biochemistry and Molecular Biology at OHSU.

Michael Matrone, Ph.D., joins OHSU as postdoctoral affairs officer

Matrone Photo for RNMichael A. Matrone, Ph.D., joined OHSU this spring to head the newly created OHSU Office of Postdoctoral Affairs. In this role, Matrone will support all OHSU postdoctoral scholars from arrival to departure and assist faculty and administrators with postdoc training and mentoring.

For postdocs, he offers individualized career advisement on topics ranging from self-assessment and career exploration to job search skills for specific career paths, as well as application preparation and review. A career resource center Matrone established in cooperation with the OHSU library is near completion and will offer electronic and print resources. Later this year, based on input from postdocs, Matrone plans to develop and offer training courses and workshops on topics including career options for biomedical Ph.D.s, career transitions, job search skills, scientific communication, and more.

For faculty and administrators, Matrone serves as a resource and adviser to help with training and mentoring of postdocs. He offers support on creating individual development plans, training grant applications, oversight on policies and procedures for postdoctoral appointments, and the onboarding and exit processes.

Matrone brings with him a great deal of experience as a former postdoc himself and as someone who established a postdoctoral affairs office at another institution. After earning his bachelor’s degree in biology from Philadelphia University in Philadelphia, Pa., Matrone worked as a research assistant at the Academy of Natural Sciences of Philadelphia, studying the population genetics of mosquitos that transmit West Nile virus. He went on to pursue a master’s in molecular biology from Lehigh University in Bethlehem, Pa., and a Ph.D. in molecular medicine from the University of Maryland, Baltimore. Matrone performed his postdoctoral studies at The Scripps Research Institute in San Diego, Calif., where he was a research fellow with the Robert E. Hewitt Foundation for Medical Research.

Through his own experience as a postdoc and involvement with the Society of Fellows, Scripps’ postdoctoral association, Matrone developed a passion for supporting postdoctoral scholars. He was hired as program coordinator in the Scripps’ Career and Postdoctoral Services office in San Diego, then transferred to Scripps Florida to open a full-time career and postdoc services office. At Scripps, he became involved in the National Postdoctoral Association and the Graduate Career Consortium, a non-profit professional organization of leaders dedicated to the career and professional development of graduate students and postdoctoral scholars. Matrone is currently treasurer on the Board of Directors of the GCC.

Contact Mike Matrone for all things postdoc at matrone@ohsu.edu or at 503-346-0361.

School of Nursing researcher to study exercise and nutrition in rural Latinas

Advertisements, news articles and entire reality TV series are based on the common knowledge that obesity, physical inactivity and a poor diet are risk factors for number of chronic illnesses and certain cancers. We also know that eating better and being active can turn those negative diagnoses around.

Cindy Perry (left) meets with community members in rural Washington State.

Cindy Perry (left) meets with community members in rural Washington State.

Cynthia Perry, Ph.D., F.N.P.-B.C., associate professor in the OHSU School of Nursing and director of the family nurse practitioner program, is taking this concept to a targeted audience with a two-year research study, “Fuerte y Sanas: Adaptation of an exercise and nutrition program for rural Latinas.” Through a grant from the National Cancer Institute, Perry is expanding on previous work promoting physical activity with rural Latino youth to introduce interventions that can reduce disparities related to physical inactivity and poor diet among Latinas in the Yakima Valley of Washington.

Census data shows that Latinas are less active and bear a disproportionate burden from physical inactivity and dietary-related negative health consequences as compared women in the general population. For example, the prevalence of obesity among U.S. Latinas is 44 percent compared with 32.6 percent in non-Latino white women. The prevalence of diabetes is 13.2 percent in Latinos compared with 7.6 percent in whites and Latino adults were 30 percent less likely to engage in physical activity.

Perry has been working with the Latina community in Sunnyside, Wash., since 2007, prior to coming to OHSU in July 2013. A former mentor worked with this community for two decades, inspiring Perry to work with this community and look at physical activity in children and now with Latina adults. She’s found that one way to address the gaps in health is to deliver culturally and linguistically meaningful interventions designed to reduce weight, increase physical activity, and improve dietary habits.

Perry’s study will entail adapting and testing a theory- and evidence-based physical activity program originally developed for rural white women. The curriculum – Strong Women, Healthy Hearts – is a 12-week exercise and nutrition program – has been shown to decrease weight, increase physical activity and improve cardiorespiratory fitness and dietary habits. Perry aims to extend the reach of the program as an avenue to addressing the health disparities experienced by this population.

Over two years, Perry will convene a community advisory board, made up of eight Latinas, to serve as a touchstone for learning what elements of the curriculum are most meaningful and how best to adapt the material for this population. She will recruit participants to attend classes two times a week for 12 weeks and measure fitness and activity level, attendance, satisfaction surveys, and the feasibility of running the program on a long-term basis. After this project, Perry hopes to write a larger grant to bring the curriculum to additional rural Latina communities in Washington, Oregon, and beyond.

Perry’s study is supported through a R03 grant 1R03CA197657-01 from the National Cancer Institute.

NIH wants your input on new child health program

The NIH is looking for input to help shape its funding priorities for new programming focused on environmental and pediatric health. If you were part of the now discontinued National Children’s Study (NCS), your feedback may be of particular interest. Moving forward, the NIH wants to leverage and expand on existing cohorts established under the NCS to address new research questions related to Environmental Influences on Child Health Outcomes (ECHO). The focus will be on longitudinal studies that will share standardized research questions across four key pediatric public health oucomes:

  • Upper and lower airway (e.g., asthma, allergies, sleep disordered breathing)
  • Obesity (e.g., nutrition, diabetes, metabolic risk factors)
  • Pre-, peri-, and postnatal outcomes (e.g., birth defects, childhood outcomes)
  • Neurodevelopment [e.g., autism, ADHD, depression, social/behavioral development, cognition]

A primary focus of this effort is to improve on measurement of environmental exposures (e.g., physical, chemical, biological, psychosocial, natural and built environments) and to create standardization and synergies across studies. A center will be established to oversee coordination and will house an analytical or data science component.

The NIH seeks comments on topics such as standardized data elements, core elements to be considered, high impact opportunities, and anticipated advances among others. Of particular interest are suggestions from existing research studies that address these topics.

Submit your comments here and be part of a large resurgent public health initiative!

OHSU researchers develop a novel gene and stem cell technique for treating mitochondrial disease

Stem cell colony

Stem cell colonies growing on top of feeder cells with immunochemistry staining

A study led by OHSU researchers Shoukhrat Mitalipov, Ph.D., and Hong Ma, M.D., Ph.D., at the Center for Embryonic Cell and Gene Therapy and the Oregon National Primate Research Center, has revealed a critical first step in developing a new gene and stem cell regenerative technique for treating patients with mitochondrial disease.

Dr Hong Ma-headshotJPG (2)

Hong Ma

Mitochondrial diseases result from DNA mutations that lead to altered cell function. Cell injury and cell death result which can lead to multiple system failure and even death.  In the United States, up to 4,000 children are born with a type of mitochondrial disease each year. There are no treatments or cures.

Mitalipov’s and Ma’s findings, published July 15 in the journal Nature, offer a potential breakthrough in treating patients with the mtDNA variant of the disease. The paper, “Metabolic rescue in pluripotent cells from patients with mtDNA disease,” outlines a mitochondrial replacement method used to create a stem cell with healthy mitochondria from a patient’s skin cell containing mtDNA mutations. To conduct this study, the researchers first collected skin cells from patients with mtDNA mutations. They then recovered the nucleus from the skin cells and paired them with healthy donor cytoplasm, the material surrounding the cell’s nucleus that contains the mitochondrial DNA, from an egg. This resulted in an embryonic stem cell with healthy mitochondria.

Shoukhrat Mitalipov

Shoukhrat Mitalipov

Reinserting genetically correct cells into the patient to replace diseased tissue is more precise than traditional gene therapy, which involves inserting synthetic genes into patients via viruses. This nuclear transfer technique could pave the way for treating many diseases caused by DNA mutations.

Read more.

The study, “Metabolic rescue in pluripotent cells from patients with mtDNA disease,” was funded by the Leducq Foundation, Mayo Clinic Center for Regenerative Medicine, OHSU and University of California, San Diego institutional funds. Work in the laboratory of J.C.I.B. was supported by the G. Harold and Leila Y. Mathers Charitable Foundation and the Leona M. and Harry B. Helmsley Charitable Trust (2012-PG-MED002).

Breaking news: U.S. House passes 21st Century Cures Act

The 21st Century Cures Act (HR 6), legislation that includes a wide range of provisions aimed at speeding medical innovation and regulatory approval, received overwhelming bipartisan support today with a vote of 344-77 in favor of passage. One hundred seventy Republicans and 174 Democrats voted in favor and 70 Republicans and 7 Democrats voted no.  Oregon’s five Members of Congress supported the legislation. The House also rejected an amendment that would have converted the NIH Innovation Fund from mandatory to discretionary funding.

The bill, if  it passes in the U.S. Senate, will provide an additional $9.3 billion in funding to the NIH and FDA and sets up frameworks to evaluate data more efficiently to better determine the safety and efficacy of new treatments. After seeking input from the medical research community, including OHSU, the House Energy and Commerce Committee incorporated additional funding for NIH at levels that represent an increase of $1.5 billion per year for three years. The bill also allows for the creation of an NIH Innovation Fund that would provide $8.75 million in funding over the next five years. The House rejected an amendment that would have converted the NIH Innovation Fund from mandatory to discretionary funding.CuresActCongress

HR 6 was introduced in an effort to improve and speed patient access to new therapies by accomplishing the following:

  • Removing barriers to increased research collaboration
  • Measuring success and identifying disease earlier through personalized medicine
  • Modernizing clinical trials
  • Removing regulatory uncertainty for the development of new medical applications
  • Providing new incentives for the development of drugs for rare diseases
  • Helping the biomedical ecosystem coordinate more efficiently to find faster cures
  • Investing in 21st century science and next generation investigators

A short summary of the bill can be found here. For additional details, read this. You can also watch Congressman Greg Walden give a shout out to OHSU for providing input and supporting this legislation.

West Nile virus vaccine developed at OHSU enters human clinical trials

Mark K. Slifka

Mark K. Slifka, Ph.D., professor and senior scientist, Division of Neuroscience, ONPRC, and Department of Molecular Microbiology and Immunology, OHSU School of Medicine

A new NIH-funded investigational vaccine to protect against West Nile Virus, discovered and developed by OHSU researchers, is entering Phase I clinical trials. The OHSU team, led by Mark Slifka, Ph.D., created the test vaccine, called HydroVax-001, with a novel hydrogen peroxide-based approach that renders the virus inactive while maintaining its integrity; an intact surface structure permits triggering of an immune response to cells infected with the virus. This preparation will allow the test vaccine to be administered to a diverse population, including those most vulnerable to the virus such as the elderly and immune-compromised individuals.

West Nile Virus first appeared in the U.S. in 1999 with 62 cases and 9 related deaths reported. It has become a significant public health concern: 41,762 cases of the disease have been confirmed in the United States since it was first reported, and 1,765 people have died from the disease. Spread through the bite of mosquitoes, West Nile Virus also infects birds and other animals. There is an effective veterinary vaccine. No human vaccine, however, has yet been approved.

In preclinical studies, the test vaccine was effective at protecting mice against a lethal dose of the virus by eliciting an immune response that killed infected cells. The clinical trial will test the safety of the vaccine and its ability to produce an immune response in humans.

The investigational vaccine was developed with funding from the National Institute of Allergy and Infectious Diseases (NIAID), and NIAID will sponsor this trial at one of its Vaccine and Treatment Evaluation Units at Duke University in North Carolina. Enrollment is expected to be completed by December 2015. holds joint appointments with the Division of Neuroscience, ONPRC Department of Molecular Microbiology & Immunology at OHSU

Who’s new at OHSU? Shawn Chavez, Ph.D.

Shawn Chavez, Ph.D., is an assistant scientist in the Division of Reproductive and Developmental Sciences at the Oregon National Primate Research Center and an assistant professor in the OHSU School of Medicine Departments of Obstetrics and Gynecology and Physiology and Pharmacology. Her paper “Prediction model for aneuploidy in early human embryo development revealed by single-cell analysis” was published online on July 7, 2015, in Nature Communications.

Chavez.2015Where were you before coming to OHSU?

I came from Stanford. Much of the work I did there was in human embryology, and my focus was on aneuploidy—the loss or gain of whole chromosomes—and how it impacts in-vitro fertilization (IVF) success. IVF has been around over 35 years and is still only 30-35% successful. One thing that’s thought to be problematic, not just with IVF, but with human fecundity in general, is why we exhibit high rates of embryonic loss following IVF as well as naturally, often even before a woman would know she’s pregnant. At least 50-80% of all embryos at the cleavage stage—that is, early cell division—will have at least one chromosome affected and will probably arrest at the 8-cell stage, making them unviable. About a million embryos are produced for IVF every year in the U.S. alone, and many of them will not result in a successful pregnancy. I want to identify those that are destined to fail before they’re implanted.

What brought you to OHSU?

There are some things we can’t do with human embryos, whether it’s procuring samples, being able to establish cell lines, or other exploratory research, so the primate center was key in my decision. I had never worked with monkeys before so coming here was a real challenge, as I had to learn about rhesus physiology. But the more I delved into the literature and the work we’re doing in the lab, the more I realized I landed in the right place. Aneuploidy rates in rhesus macaque are very similar to those in humans and female rhesus macaques have comparable reproductive physiology and cycles to human females. Also, there are strict timing intervals of mitotic divisions that indicate whether an embryo will be chromosomally normal or abnormal. These intervals may be slightly faster in the macaque but the dynamics are identical. By contrast, though much research in this area has been conducted using a mouse model, mice exhibit only around 1-10% aneuploidy. Macaques are the perfect model for my work and unlike mice, are released back to the colony following IVF.

What specific avenues of research are you exploring?

Examining cellular fragmentation more closely. Between the 1 and 2 cell stage is when you see these fragments form. They appear as small cytoplasmic balls that were thought to be empty, but we now know they can contain chromosomes. It appears fragmentation is in response to aneuploidy. What we don’t know is it trying to correct aneuploidy or trying to initiate its demise?

Rhesus embryo with fragmentation Photo by Cathy Ramsey

Rhesus embryo with fragmentation
Photo by Cathy Ramsey

DNA sequencing can now be done on a single cell level. So what we’re doing is taking 8 cell embryos and disassembling them into single cells and single fragments. In collaboration with Lucia Carbone, who investigates chromosomal rearrangements, we are DNA sequencing the whole embryo to try to reconstruct what has happened. Is there a mitotic or a meiotic error? Are there whole chromosomes or pieces missing? What is the structure of the chromosomes that remain? These are things we don’t know and are trying to find out. Being able to combine a single cell approach to answer some of the basic questions with time-lapse imaging, DNA sequencing, and gene expression allows us to correlate the data to get an idea of the full dynamic. We then hope to use these results to determine whether there are natural mechanisms such as multi-polar cell divisions or the resorption of fragments that we could exploit or other potential therapeutic interventions for improving IVF success.

We’re also looking into the male’s contribution to aneuploidy, which I think we have probably underestimated in the past.

Read more…

Workshop on reproducible research, July 22

Reproducible research provides transparency that fosters credibility and allows others to replicate findings and build on them. Recent challenges with reliability of published findings led the NIH to issue new requirements designed to enhance reproducability and various scientific journals, including Nature, have introduced new editorial methods to address the problem. But what specific measures should researchers take to meet these new standards?

Advanced software products can be used to help investigators adopt reproducibility into their research. One such tool is knitr, a package within the R statistical programming environment. Knitr uses Literate Programming to allow for results to be published alongside documentation of the steps that produced them. Curious to know how this tool can benefit your research? Attend the following workshop:ScienceCat (2)

Reproducible Research with R’s knitr package
Wednesday, July 22
2 to 3 p.m.
Vollum Institute, M1441

Presented by the OHSU Center for Health Systems Effectiveness, research associates Ben Chan, Stephanie Renfro, and Thomas Meath will review Literate Programming principles and discuss specific tools to help improve reproducibility.

 

 

Welcome to the Research News Blog

Welcome to the Research News Blog

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