Learn about new technologies and sequencing services in the Integrated Genomics Lab Cores

Join Bob Searles, Massively Parallel Sequencing Shared Resource, and Chris Harrington, Gene Profiling/RNA and DNA Services Shared Resources, who will discuss new genomics technologies available in the cores. Among the new services to be discussed: RNA-seq from FFPE tissue, miRNA sequencing, high throughput DNA and RNA extraction, cell-line authentication, and single cell RNA-seq. All members of the OHSU community are invited to attend.  The Integrated Genomics Lab cores are members of the OHSU University Shared Resources Program.

Thursday, July 7
10 to 11:30 a.m.
Rirchard Jones Hall, room 4320

The presentation will last an hour followed by 30 minutes of Q & A.

Who’s new at OHSU? Sudarshan Anand

Sudarshan Anand, Ph.D., is an assistant professor in the School of Medicine’s Departments of Cell, Developmental & Cancer Biology and Radiation Medicine. He arrived at OHSU in March 2014 and is one of a team of researchers at OHSU examining factors that shape the tumor microenvironment.Anand, Sudarshan

Where are you from originally and what shaped your early career?
I was born and raised in India and came to the U.S. in 2001 for graduate school. I started out the University of Maryland in cell biology but quickly realized I wanted to work in immunology, so I moved to the Mayo graduate school and worked with Dr. Lieping Chen. When I joined his lab, he had just discovered PDL1, which is involved in the immune response to tumors. When Dr. Chen moved to Johns Hopkins, I went with him. I joke that my Ph.D. degree comes with standard error bars because I did it three times! After graduate school, my mentor told me that if I wanted to do cancer research, I needed to expand beyond immunology, and I took that to heart so I completed my postdoc working with David Cheresh at UCSD who is an expert on tumor blood vessels (angiogenesis). This experience shaped my future research.

What brought you to OHSU?
When I was looking for a faculty position, I knew OHSU would be the right place to start the research program I wanted to build. My decision was based on a combination of faculty expertise and the institutional culture here. I love the vision of my chair Dr. Lisa Coussens in building a unique research hub centered on the tumor microenvironment. I also greatly appreciate the collaborative nature of OHSU. I’ve had help from a number of people in starting my lab, recruiting staff, getting clinical samples. It’s particularly unique to have access to this expertise and the amazing resources here as a junior faculty member. Also, this is a rather special moment for the Knight Cancer Center. It’s great to be participating in the process of rapid growth of an institution.

What is the current focus of your research?
The major focus of our lab is in understanding small RNAs or microRNAs in blood vessels and how they respond to DNA damaging agents such as radiation. Primarily we’re looking at blood vessel cells in cancer; they’re a unique species. In adults, blood vessel cells rarely divide because we don’t have the need to build new ones unless an area is affected by injury. But blood vessel cells in cancer, by nature of what they’re supplying, constantly divide and don’t have enough time to form properly. So these vessels are irregular and often not good at delivering blood. This creates a problem for a couple of reasons – one, you decrease the oxygen being delivered to the tumor. Under these conditions, any normal cell would starve and die but cancer cells have special adaptations that make them more aggressive in that situation. Cancer cells starved of metabolic pathways, tend to be the ones that metastasize and travel to distant targets. Two, once you have lower perfusion in the tumor, chemotherapy drugs don’t get to all the cancer cells and radiation therapy doesn’t work as effectively.

Why study microRNAs?
Generally microRNAs are small RNAs encoded in our genomes that function to decrease gene expression and protein output in cells. But many of the targets of these microRNAs are in a related pathway, so if you take away 25% of protein A, B and C, but A, B and C function in the same pathway, you have a geometric progression of effects, and the whole pathway is significantly impacted. So we have done a number of microRNA profiles of blood vessel cells (endothelial cells) and have developed 1-2 microRNA candidates that appear to have significant biological effects in mouse tumor models.

Now our goal is to a) understand these microRNAs – to find out if they play a role in response to certain therapies and b) identify if we can use some of them for diagnostic purposes. The hope is that we will be able to develop predictors, for example, in blood to know which patients will and will not respond to specific therapies. And if they’re not going to respond, we can put them on an alternative therapy and save them from side-effects of radiation exposure or specific chemotherapies. This is the focus of a project we’re doing in collaboration with Dr. V Liana Tsikitis, an associate professor of surgery here at OHSU. She has a cohort of patients with rectal and colorectal cancer. Many patients with this type of cancer receive radiation to shrink the tumor and then surgery to remove it. But roughly 30% of patients don’t respond to the radiation. If we can predict which patients will not respond from a biopsy, we may be able to avoid radiation toxicities or have them on other therapies to shrink the tumor before surgery. So we’ve done microRNA profiles on biopsies of patients who have and have not responded to chemoradiation and generated some preliminary data that suggest we’ll be able to identify meaningful signatures. We hope to eventually move this to a Phase I trial.

View SnapshotTherapeutic application is a few years away but we’re moving in the direction of manipulating the microRNAs in blood vessel cells to potentially shift the balance by either inducing more cell death or preventing blood vessel cells from dying. If we found 3 or 4 microRNAs were lower in patients who responded better to a specific treatment, can we knock it down in a cell culture in tumors where there is poor response and convert these tumor cells into better responders? There is a lot of excitement in the field right now because the first phase I trial to test the premise that you can inject microRNA agents into patients, get them into cells, and have them well tolerated and safe is already underway.

One of the more advanced projects we’re working on is examining a microRNA that targets a protein implicated in lupus, a disease characterized by a particularly strong autoimmune response against the body’s own cells. What we’re trying to do is essentially create lupus in the blood vessel cells of a tumor. This is a high-risk strategy because you want the delivery specific to the blood vessels in the cancer, not throughout the body. So, we’re working with a collaborator at MIT who has created a nanoparticle that delivers only to blood vessel cells, and this particular microRNA only works in dividing blood vessel cells. Again, since most normal blood vessel cells are not dividing at any given moment, this mitigates some toxicity concerns. But we are always on the look out to deliver RNAs precisely to different cells that are within a tumor.


Anand lab members enjoying time away from the bench.

If you had no constraints on resources, what research problem would you try to solve?
Without a limit on resources and technology, I believe we would tackle cancer in a different way. We would engineer cells or even nanoparticles to spy on tumors, report what’s going on at all times, and equip them with the ability to take action and kill cancer cells. It’s like designing the “James Bond” of cells. As an example of what I mean by reporting: cells could be programmed to produce a synthetic molecule when triggered by enzymes shed by cancer cells. Imagine if this molecule would show up in, say, urine or blood long before a metastasis shows up on a scan. Patients with a high risk of recurrence or relapse could have simple, at-home diagnostic tests they can use once a week, and if they see a signal, schedule a visit for follow-up. This could become a reality in a decade or so.

Tell us something about yourself that’s not on your resume
One thing that really influenced my decision to pursue a career in science was the opportunity I had to do research in a lab early on, even as a high school student. So I’m very committed to outreach and communicating the excitement of science. I have two summer interns and a high school student in the lab. In addition to teaching them to do the science, we also try to teach them how to communicate science and work in teams, understand career paths in science etc. It’s never too early to be introduced to these concepts.

Outcomes for second-time R01 resubmissions

It’s been over two years since the NIH revised their grant resubmission policy. This revision allows applicants whose R01 application (called an A0) and subsequent resubmission (an A1) are unsuccessful to submit a new application without having to demonstrate significant changes in scientific direction from the previously reviewed applications. When the policy went into effect in April of 2014, there was a sigh of relief but also uncertainty about how these “new” applications, now referred to as “virtual A2s,” would fare.

In a June 24 Open Mike blog post, NIH’s Deputy Director for Extramural Research, Michael Lauer, analyzes the data, showing the changed policy has slightly increased the success of second-time revisions.


Events following unfunded A1 applications. Baseline: unfunded R01 applications in FY2014; subsequent application: at least one R01 or R21 application submitted by a PI in the baseline group; “virtual A2”: at least one subsequent application/award with text that significantly matched with the baseline group; “nonmatching”: at least one subsequent application/award without a significant text match in the “baseline” group. June 24, 2016 Open Mike.

Lauer and his team used text-mining software to identify these virtual A2s and to describe their review outcomes compared to other submissions from the same investigators. Following is a summary of their findings:

  • Investigators are taking advantage of the new policy. For about 22% of unsuccessful A1 applications, NIH receives a materially similar subsequent submission, a virtual A2;
  • PIs were more likely to submit a virtual A2 if their unfunded A1 had been discussed and received relatively favorable scores;
  • Investigators who fail to obtain funding on an A1 remain active. 80% of the PIs with unsuccessful A1 applications submitted at least one application within the following fiscal year;
  • New investigators are less likely to submit virtual A2s; and
  • Of the cases in which at least one virtual A2 application was submitted, 20% had at least one application funded.


Limited submission funding process refresher

Faculty and departments have recently been asking “What should I do when I’m applying for a grant and I notice that only one application is accepted per institution?” To clarify what’s involved in identifying and applying for limited submission funding opportunities, the following information should help those of you who are new to the process and anyone else who may need a refresher.

What is a limited submission?
Limited submission funding opportunities are programs in which the sponsor sets a limit for the number of applications or proposals an institution can submit (typically 1 to 2). Institutional coordination is required to ensure fairness, transparency, and adherence to the sponsor’s requirements.

How are applications or proposals selected by the institution?
OHSU’s Limited Submission Program is a service of the Office of the Senior Vice President for Research to help faculty identify limited submission opportunities and to coordinate internal reviews. The review process is conducted by OHSU’s Limited Submissions Committee, composed of 10 senior faculty members, which makes recommendations to the SVPR regarding which applications should move forward as proposals to external sponsors. Internal applications are ranked according to criteria established by the sponsor as well as on the merit of the proposal and principal investigator.

How do I know if a funding opportunity is a limited submission?
All limited submission opportunities are posted on the OHSU Internal Funding Database. You can identify these opportunities in the “Internal Coordination” column when you search the database:


As a general rule, it’s advised to check the eligibility criteria provided by the sponsor in the Request for Proposals or Applications (RFP or RFA) before working on a submission. This is where you’ll find the most complete information on PI requirements and whether the sponsor is limiting the number of applications OHSU may submit.

How do I submit a limited submission application for consideration?
Refer to the OHSU Internal Funding Database to determine the deadline for submitting your internal proposal. This deadline is set roughly four to eight weeks before the sponsor’s external deadline to allow time for review and for the nominated PI(s) to prepare a full proposal. Interested candidates must complete an application via the Competitive Application Portal (CAP). This online application provides basic information for the review and selection process. You will attach the following materials to your application:

  • Curriculum vitae (CV) or Biosketch
  • 1- to 5-page summary of candidate’s research proposal– This document can be written in NIH style but should be written in a manner readable by a group of educated interdisciplinary scientists. Avoid using jargon, and assume that no reviewers are specialists in your field.
  • Letter of support/recommendation from a department head, chair, mentor, or other appropriate person. In many cases, this letter is optional, but the review committee finds letters helpful. The letter should detail your strengths and can be used in your full application, if selected to submit.

If you have any questions on the limited submission process, please email funding@ohsu.edu or call 503 494-0107.

OHSU startup presents at largest U.S. biotech conference

Dave FarrellGamma Therapeutics, Inc., an early stage OHSU biotech startup company, was selected by the National Science Foundation (NSF) as one of 50 companies to exhibit and showcase their technology in the world’s largest biotech conference. Held June 6-9 in San Francisco, the Biotechnology Innovation Organization (BIO) International Convention attracted nearly 15,000 biotech leaders from over 65 countries. The event covered the wide spectrum of life science innovations and application areas, including drug discovery, bio manufacturing, genomics, biofuels, nanotechnology, and cell therapy. Gamma Therapeutics Founder and Chief Scientific Officer, David Farrell, Ph.D., F.A.H.A., represented the company as one of the few Oregon-based companies at the BIO Convention.

BIO recognized Gamma Therapeutics for the company’s recent NSF STTR Phase I award. Gamma’s products, which are based on OHSU technologies, are in the cardiovascular disease risk assessment, surgical therapy and combat casualty care spaces. The NSF STTR grant was awarded to develop a physiological initiator protein to enable rapid blood clotting to treat bleeding after a traumatic injury. Other products in Gamma Therapeutics’ product line include its flagship product, GammaCoeur ™, a cardiovascular disease risk diagnostic assay; GammaSeal™, a patented, high-strength post-surgical incision sealant; and Gammarin™, a patented non-immunogenic blood anti-coagulant.

Farrell hopes to bring more recognition and partners to the State of Oregon. “This was a great opportunity to bring international attention to the high quality of new inventions and discoveries coming out of Oregon, which could attract strategic industry partners and venture investment to Oregon.”

Resources for research with nonhuman primates

Have you ever thought about or are you planning to engage in primate research? The National Primate Research Centers (NPRCs) serve as a unique and valuable national resource to scientists who currently use or are considering using nonhuman primate models in biomedical research. If you have questions about nonhuman primate animal models of human disease or want to learn how the NPRCs can support your research, visit NPRCresearch.org. The contact page includes direct links to all seven NPRC websites as well as information for local contacts at each center including the Oregon National Primate Research Center.

Recent updates to NRPCresearch.org include:

  • Hot Topics written by the NPRC directors and core scientists regarding the latest nonhuman primate research on developmental and acquired diseases, including Zika virus, HIV, and autism spectrum disorder
  • Searchable listings of NPRC-related publications, 324 of which have been released in the last six months
  • New information about Pilot Research Program funding available at the NPRCs
  • And more…

Explore the many ways the NPRCs can help you achieve your research goals at NPRCresearch.org.

OHSU investigators uncover factors driving “low-value care”

Waste accounts for roughly 20 percent of spending in the U.S. health care system. A significant portion of that waste is attributed to low-value care – unnecessary tests and treatments that are not only costly but provide little clinical benefit or may even harm patients. However, little was known about the patterns and drivers of this type of care. In a first-of-its kind study, researchers from OHSU’s Center for Health Systems Effectiveness (CHSE), compared low-value care among more than 1.6 million Medicaid and commercially insured patients in Oregon. They found no association between insurance type and low-value care, with Medicaid patients more likely to receive some low-value services but less likely to receive others.

Commercial reimbursement rates are generally much higher than Medicaid rates, so co-authors of this study, Christina Charlesworth, M.P.H., research associate, and John McConnell, Ph.D, associate professor in the School of Medicine’s Emergency Medicine Department and CHSE director, were a “little surprised” to find no consistent association between insurance type and low-value care.  They did find an association between low-value services and geographical practice areas, indicating this care may be more closely related to local norms or access to equipment than to reimbursement generosity or insurance benefit structures. Results of this study, published in JAMA Internal Medicine, provide key information for the medical community, policy makers, and patients in their efforts to improve value in health care.

OHSU researchers develop new technique for selecting gene-corrected cells

Gene therapy offers great promise for treating genetic disorders and in repairing or correcting injury and disease. However, efforts to modify and expand the pool of gene-edited cells to reach therapeutic levels have proved challenging to date. Current methods are not only time consuming and expensive, but also present a risk to the patient. Now a team of researchers led by Sean Nygaard, B.S., M.Div., senior research associate in the Markus Grompe Lab at OHSU’s Oregon Stem Cell Center, has developed a new technique that may help overcome this hurdle. In the June 8 edition of Science Translational Medicine, Nygaard details a new platform technology that selects for gene-edited cells in vivo, allowing therapeutic levels of healthy cells to survive when subjected to toxic drugs such as those used in chemotherapy.

In this study, Nygaard, Markus Grompe, M.D., and colleagues injected cells that had been genetically modified to be resistant to a toxic drug, CEHPOBA, into the livers of live mice. They then treated the animals with CEHPOBA or saline for several weeks. They found that those treated with the drug saw an order-of-magnitude increased trans-gene expression compared with the mice treated with saline. So by treating a population of liver cells with the drug, the researchers ensured that only the gene-corrected cells survived and repopulated the liver.

This universal method of selection can be used to support cell-based treatments for genetic disease such as hemophilia B and metabolic liver diseases, or extended to any tissue that proliferates after injury, including the bone marrow and skin, Nygaard’s study found.

Nygaard was first author on this paper, “A universal system to select gene-modified hepatocytes in vivo.” Grompe was corresponding author. Coauthors are Adi Barzel, Ph.D. formerly at Stanford University School of Medicine (currently at Tel Aviv University), Annelise Haft, senior research assistant in the Grompe Lab, Angela Major, Baylor College of Medicine, Milton Finegold, M.D., Baylor College of Medicine, Mark A. Kay, M.D., Ph.D, Stanford University School of Medicine.

Planning for an animal facility emergency or disaster

Any research animal housed in an OHSU animal facility could eventually be affected by an emergency or disaster. New federal regulations require institutions to “establish a disaster plan in conjunction with the responsible investigators, taking into consideration both the priorities for triaging animal populations and the institutional needs and resources. Animals that cannot be relocated or protected from the consequences of the disaster must be humanely euthanized” (from The Guide for the Care and Use of Laboratory Animals, 8th Edition.) If an earthquake, fire, or other event affects OHSU’s animal facilities, quick decisions will need to be made about what to do with the animals, especially whether animals could be safely moved to another campus animal housing area. Appropriate housing space would likely be limited, and animals would need to be triaged, making it necessary to humanely euthanize some populations and move others to a safe location.

Therefore, all principal investigators using animals for research should develop a triage plan for irreplaceable animals that are currently housed at OHSU.

To help with this effort, the Department of Comparative Medicine (DCM) is providing gold stars that can be attached to the cage cards of animals deemed most important by PIs. In conjunction with research staff, DCM will make every reasonable effort to protect or move the identified cages. These stars can be obtained from the DCM office in Biomedical Research Building, room B110.

In the event of a disaster or emergency, please be aware that there may be limited housing areas available. Depending on the type and severity of the event, the possibility also exists that no suitable housing would be available. With this in mind, limit the marking of cages to the minimum number needed with no more than five total per protocol.

Also, PIs should consider cryopreserving valuable or irreplaceable strains through the OHSU Transgenic Mouse Models Core Facility. Arrangements for rodent cryopreservation can be made by contacting Dr. Lev Fedorov.

Contact information for all PIs and PI staff must be kept current within the animal facilities and in the eIACUC so that facility personnel are able to be reached in case of an emergency.

Question? Contact Kim Saunders at saunderk@ohsu.edu.

Data Jamboree: Code Your Graph, June 24

This Friday’s Data Jamboree is devoted to techniques and tools for data visualization. Bring your laptop for hands-on tutorials on ggplot and matplotlib. A keynote talk on visualizing high dimensional data will also be presented by Kemal Sonmez, Ph.D., associate professor in the School of Medicine’s Computational Biology Program, and Julja Burchard, scientific director of the Bioinformatics Core. Everyone is welcome!CodeYourGraph

June 24, 2:30 – 5:00 PM
OHSU Auditorium

Arrive by 2:30 for help installing software packages! Food & drink will be provided. Sponsored by Computational Biology & the OHSU Library.

Questions? Contact sonmezk@ohsu.ed or margolin@ohsu.edu.

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