Co-invented by OHSU’s David Huang 25 years ago, OCT technology helps detect and stop blindness

This year marks the 25th anniversary of the invention of Optical Coherence Tomography technology, co-invented by Oregon Health & Science University Casey Eye Institute’s David Huang, M.D., Ph.D., while Huang was a Ph.D. student with James Fujimoto, Ph.D. at Massachusetts Institute of Technology. To commemorate the anniversary, the Association for Research in Vision and Ophthalmology (ARVO) published a special anniversary edition in their journal Investigative Ophthalmology & Visual Science with more than 70 articles.

David Huang, M.D., Ph.D., and his team at the Center for Opthalmic Center for Ophthalmic Optics and Lasers Lab, or COOL Lab, at Casey Eye Institute

David Huang, M.D., Ph.D., and his team at the Center for Opthalmic Center for Ophthalmic Optics and Lasers Lab, or COOL Lab, at Casey Eye Institute

OCT is the most commonly used ophthalmic diagnostic technology worldwide, with an estimated 30 million OCT imaging procedures performed every year. The technology has evolved over the past 25 years to help diagnose and treat the most common causes of blindness: age-related macular degeneration, diabetic retinopathy and glaucoma. OCT use continues to grow exponentially in ophthalmology and other medical specialties, including cardiology, dermatology, neurology, and gastroenterology.

OCT has transformed the way ophthalmologists are able to diagnose, monitor and treat devastating eye diseases, and it has advanced drug discovery and development. The technology is particularly suitable for the early detection of glaucoma and macular degeneration, diseases that may cause significant damage prior to the appearance of symptoms. OCT is also widely used for diabetic macular edema, the leading cause of blindness in young patients.

“Dr. Huang’s contribution to the field of ophthalmology has been tremendous and we are very fortunate to have such a brilliant mind here at Casey Eye Institute and in Oregon,” says David J. Wilson, M.D., director of the OHSU Casey Eye Institute and chair of the Department of Ophthalmology in the OHSU School of Medicine. “This anniversary is a perfect opportunity to celebrate OCT as a truly transformative medical technology. Such transformations do not occur often in medicine.”

OCT technology has also evolved over the past 25 years with great advances in imaging speed and quality. Ophthalmologists can now study disease at the microscopic level without biopsy, and with complete patient comfort. For the first time, eye physicians can visualize and measure blood flow in the smallest of blood vessels, without the need to inject contrast agents.  Non-invasive visualization and measurement of blood flow gives great insight into the cause and progression of eye disease.

Huang, who was recently ranked the 4th most influential figure in the world of ophthalmology by The Ophthalmologist PowerList 2016, runs the Center for Ophthalmic Optics and Lasers Lab, or COOL Lab, at Casey Eye Institute which includes a team of top scientists from around the world who have been perfecting OCT technology for more than 15 years. Several members of the lab have contributed articles for the special issue in IOVS (see Related Content for links to articles).

Key OHSU collaborators with Huang’s lab include Ou Tan, Ph.D., John C. Morrison, M.D., Yali Jia, Ph.D., Winston Chamberlain, M.D., Ph.D., Steven Bailey, M.D., Thomas S. Hwang, M.D., and Douglas D. Koch, M.D. at Baylor College of Medicine in Houston.

The papers published in the ARVO special issue by OHSU faculty were supported by the National Institutes of Health, Research to Prevent Blindness, Optovue, Inc. and the Oregon Clinical and Translational Research Institute.

Change to eligibility for NSF graduate research fellowships

If you are a graduate student applying for the National Science Foundation Graduate Research Eligibility Program, you should be aware of an impending change in eligibility.

nsf1 Program solicitations for the NSF GRFP are due to be released in late July or early August. Effective as of the 2017 competition (deadlines in late Oct. or early Nov. 2016, based on discipline), graduate students will be limited to only one application to the GRFP, submitted in either the first or second year of graduate school. The intent is to increase the number of applicants applying as senior undergraduates, a population that’s more diverse in terms of women, underrepresented minorities, persons with disabilities and veterans, as well as to ease the workload for applicants, reference writers, and reviewers.

How will this impact OHSU’s graduate students wanting to apply to the GRFP? The new rules are being phased in so if you applied as a first-year graduate student in fall 2015, you are eligible to apply this fall as a second- year graduate student. Likewise, if you applied as an undergraduate, as soon as you begin graduate school, you can submit again but only once:  as either a first- or second-year graduate student. Work closely with you advisor to determine if you’ve demonstrated sufficient achievement in your first year to be competitive or whether your application would be stronger the following year. If you have additional questions about this new rule, check out NSF’s FAQ’s on this rule change.

Still have questions? Contact us at

Who’s new at OHSU? Nathalie Pamir, Ph.D.

Nathalie Pamir, Ph.D., is an assistant professor in the School of Medicine, Knight Cardiovascular Institute (KCVI), where she focuses on preventive cardiology.

Where are you from originally?
I’m from a Russian family but I was born in Turkey and spent my childhood there. I then went through the French school system and returned to Turkey to get my undergraduate degree. From there I moved to Vancouver, B.C., where I earned my master’s degree at the University of British Columbia and finally my doctorate degree at the University of Washington. This is also where I completed my postdoctoral research.pamir

What brought you to OHSU?
I was ready to move. I felt like I needed a change for myself and new openings for my research.  I immediately saw the benefits. At OHSU I have access to human samples that would have been very difficult for me to get at UW. Here that resource is much more available and people expect you to do something with it. [KCVI] is an institute very much embedded in a clinic environment. I moved from basic science to translational work in a year and that’s because of how KCVI is structured. I go to staff meetings where I’m sitting next to cardiologists and I get to hear what they’re doing and observing and if I ask a question, people will direct me to the right people or resources. People here don’t mind sharing.

What is the focus of your research?
I’m currently working on two separate but related areas: cholesterol and adipose tissue, or body fat. On the cholesterol front, we want to know:  Is good HDL really good? If so, why? Or have we found a way through our lifestyle to make it bad so it’s no longer working? We do know that HDL levels have a hereditary component; roughly 50% is unchangeable. So you can only modify the remaining 50%. You can think of HDL particles as tiny balls, about one thousandth the size of a cell nucleus, infiltrating every tissue in the body, removing cholesterol from cells and bringing it back to the liver. That’s their job.  Historically we always cared about the number of “balls” but that’s now considered irrelevant because so many studies have shown that raising HDL levels does not necessarily provide cardiovascular benefits.

The discussion now is around how efficient, how good these particles are at removing cholesterol from cells and bringing it back to the liver. Testing for function isn’t at the clinical level yet but there are four large epidemiology studies looking at HDL function and cardiovascular risk. What I want to know is the function genetically regulated? If so, what’s the wiggle room for improvement? I currently have an American Heart Association Scientist Development Grant to look at HDL proteome (a set of proteins expressed) and function across hundreds of strains of mice. I’m using a genetic tool developed by UCLA that allows you to map a phenotypic trait, say HDL function, and then identify a couple of genes that associate with that trait – so, these genes regulate that trait. In my studies I’ve shown that HDL function and HDL proteome are genetically regulated. The most amazing part is that just by looking at the HDL proteome of 80 to 100 proteins, you can predict the genealogy of a trait with statistical analysis.

Another interesting area I’m exploring is we know HDL function correlates with CVD but in most cases, it’s not the CVD that kills you, it’s a stroke event. But why? The relationship between HDL cholesterol and stroke is not very well defined. So I’m working with Nabil Alkayed, M.D., Ph.D., director of the Division of Cerebrovascular Research in the OHSU School of Medicine to better understand this link. We tested 15 patients and found a tremendous difference not only in HDL function but also in the HDL proteome. The reason that’s important is we believe protein dictates function. If we understand what these HDL “balls” are made of protein-wise then maybe we can understand why they’re good at, or failing, at their function. Sergio Fazio M.D., Ph.D., head of preventive cardiology introduced me to REGARDS (Reasons for Geographic and Racial Differences in Stroke) researchers and I’ve been granted access to samples from this large epidemiology study to further explore this research question. I have 3,000 samples total – 1,000 healthy, 1,000 CVD, and 1,000 stroke to look at HDL biology, function, proteome, and genetics. Now I need to do the science and have requested funding from NIH.

My work examining adipose tissue focuses on metabolism. Why do we get fat? What happens in the body when we get fat? Again, the tool we use to answer these questions is to study the structure and function of proteins, proteomics. We recently developed the first reliable proteomics method for examining adipose tissue and I’m writing my first paper on this new method at the moment. Until now there were no reliable methods for identifying proteins in adipose tissue, not even in mouse models. But because I used proteomics to study HDL, I knew how disassociate lipids from proteins and I transferred that expertise to adipose tissue. Now we can get lipids out of the way so we can study the proteins.

I’ve also teamed up with Wohaib Hasan, Ph.D, another investigator here at KCVI, who receives donor hearts for his research. We’re looking at epicardial fat, the fat around the outside of the heart, in both “healthy” hearts and those that have failed. We know the volume or mass of that fat increases with age and with obesity. But it’s also a separate risk factor for cardiovascular disease, even in the absence of other risk factors such as age and weight and we don’t know why that is. In the past, we could only study epicardial fat through non-invasive external investigation but now, for the first time, we have proteomics as a tool to look more closely at this fat and what it secretes. Amongst all the proteins identified with this new method, we hope to pinpoint the culprit(s) causing the heart to malfunction. The plan is to do a screen of the tissue, the secretome, and of the group of proteins that get packed into tiny vesicles called “exosomes” that enter the blood stream and appear to be programmed with a destination. I have shown that when comparing adipose tissue and muscle, adipose tissue secretes quite a bit within 2-3 days of culture while muscle continues to secrete. We surmise epicardial fat secretes proteins, via exosomal particles, that cause endothelial dysfunction in the heart or smooth muscle abnormalities that can cause heart failure.

This is a hypotheses that we’re now equipped to test. Proteomics is a kick start. We can see which proteins are in the tissue, in the secretome, and in the exosomal vesicles, and then test changes to them in assay: Does x do something to the function? Does y change the health of endothelial cell? If we know what’s coming out of epicardial fat, what is unique to that fat, and what’s causing harm, the hope is that one day we’ll be able to identify it in plasma. This could potentially produce a biomarker for heart failure. We might also find that the damage is specific to a close-proximity effect, in which case maybe we take a pharmacological approach that targets that specific protein.

Portland or Seattle?
I like Portland much better. I grew up in Istanbul and was educated in Paris. Both places are very neighborhood-driven cities and that neighborhood aspect…. I found it here in Portland. It feels much more European to me. It feels almost like home.

Study led by OHSU researchers provides evidence of immune therapy efficacy in treating metastatic prostate cancer

Programmed cell death 1 (PD-1) inhibitors have shown anti-tumor activity in patients with melanoma, renal cell, non-small cell lung cancer, and bladder cancer. However, patients with castration-resistant prostate cancer demonstrated no response to such immunotherapies in past studies. Now, a research team led by Julie Graff, M.D., assistant professor and oncologist with the Knight Cancer Institute, has shown clear evidence of meaningful clinical activity for PD-1 blockade in men with metastatic prostate cancer resistant to androgen deprivation.

The team’s paper, published on July 13 in Oncotarget, outlines the study involving 10 men with metastatic prostate cancer who were treated with pembrolizumab, a monoclonal antibody that binds to the PD-1 receptor. Three of the first 10 participants enrolled in the ongoing clinical trial experienced rapid reductions in prostate specific antigen, or PSA, an early measure of treatment effect. The participants who responded to PD-1 blockade started with serum PSA levels of 46, 71 and 2,503 ng/ml. These PSA levels plummeted to less than 0.1 ng/ml after treatment, and these three patients remain free of progression at 30, 55 and 16 weeks of follow-up, respectively.

“It’s pretty remarkable, especially in light of the fact that many people doubted this approach could work at all,” said Graff. “You don’t get responses like this with almost any other treatment.” The study’s authors note these results are preliminary but the surprising and robust responses seen in this study warrant to re-examination of PD-1 inhibition in prostate cancer. Future studies are in the planning stages.

Read the full press release here.

In addition to lead author Graff, the following OHSU investigators contributed to this study: Joshi Alumkal, M.D., George Thomas, M.D., Jeremy Cetnar, M.D., M.S.H.P.R., Frederick Ey, M.D., F.A.C.P., Raymond Bergan, M.D., Rachel Slottke, and Tomasz Beer, M.D., F.A.C.P. Additional authors include researchers from the VA Portland Health Care System, Johns Hopkins University School of Medicine and the Providence Portland Medical Center.

Supported in part by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp. Funds from the Bloomberg Kimmel Institute supported a portion of the laboratory work.

Grompe lab discovery offers new clues to diabetes causes and treatment

Diabetes affects nearly 30 million people in the United States. The disease is caused by dysfunction or loss of insulin-producing beta cells that normalize blood sugar levels in the body. Until now, only one type of beta cell was known to exist. But OHSU researchers have developed a method allowing them to identify and isolate four separate subtypes that differ in their susceptibility to metabolic stress and their capacity to proliferate or change from one cell type to another. The results of their research, published July 11 in Nature Communications, may provide new and important avenues for research and treatment of diabetes.

“This study marks the first description of several different kinds of human insulin-producing beta cells,” said Markus Grompe, M.D., principal investigator, director of the Oregon Stem Cell Center at OHSU and the Papé Family Pediatric Research Institute at OHSU Doernbecher Children’s Hospital. “Some of the cells are better at releasing insulin than others, whereas others may regenerate quicker. Therefore, it is possible that people with different percentages of the subtypes are more prone to diabetes. Further understanding of cell characteristics could be the key to uncovering new treatment options, as well as the reason why some people are diabetic and others are not.”

The paper, “Human islets contain four distinct subtypes of cells,” was supported by the National Institutes of Health (Grant #s DK105831 and DK089569) and the Helmsley Trust. Craig Dorrell, Ph.D., and Grompe co-wrote the manuscript. Additional researchers from OHSU, the University of Pennsylvania School of Medicine, and the University of California, San Francisco contributed to this study.

Proposal development webinar for clinical, population, and comparative effectiveness researchers, July 8

Are you an investigator in clinical, population or comparative effectiveness? Do you want to learn more about developing successful proposals to move your research forward? Come hear from experienced scientific investigators who are part of Accelerating Data Value across a National Community Health Center Network, or ADVANCE.

The ADVANCE Clinical Data Research Network is led by Oregon Community Health Information Network, or OCHIN, in partnership with Oregon Clinical & Translational Research Institute, Health Choice Network, and Fenway Health. The goal of the Clinical Data Research Network is to build and maintain a “community laboratory” of Federally Qualified Health Centers serving safety net patients, including the uninsured, the under-insured, undocumented immigrants, and other vulnerable populations. The Research Data Warehouse maintains data on over two million patients and is the nation’s most comprehensive dataset on care and health outcomes in safety net patients. Research conducted in this dataset has the potential to address myriad questions about improving care quality and outcomes among our nation’s most vulnerable patients.

Friday, July 8
Noon to 1 p.m.
Register here.

During this webinar you will:

  • Hear from investigators whose proposals for comparative research funding have been successful
  • Learn more about using the ADVANCE data warehouse
  • Network with other investigators in the ADVANCE network
  • Ask specific questions pertaining to your research and barriers to successful proposal development

New services for OHSU entrepreneurs

Entrepreneurs at OHSU: you now have access to technology development resources via a new agreement with Virogenomics BioDevelopment, a 2015 spin-off of OHSU and Virogenomics, Inc. Working with universities across Oregon, biotech companies, and national institutions, Virogenomics brings together the scientific, regulatory, and funding components necessary to move technology out of the lab and into the marketplace. The idea is to help investigators find solutions to common problems such as applying for and managing STTR/SBIR grants, obtaining independent analyses of technologies and markets, and creating commercialization pipelines. The expectation is that the STTR/SBIR services will be especially helpful for OHSU entrepreneurs because it allows them to apply for funds without the complications and risk of creating a new business with an unproven technology.

Through this collaboration, both OHSU and Virogenomics BioDevelopment are working together to identify technology projects of mutual interest. OHSU researchers who are developing early-stage technologies and want to obtain funding to move forward are the ideal beneficiaries of this partnership.

Virogenomics BioDevelopment’s portfolio includes the spin out of four startup companies. One of these is OHSU spinout Artielle ImmunoTherapeutics, a privately-held, clinical-stage pharmaceutical development company. Under their management, Artielle has raised $19 million in venture financing to complete a Phase 1 clinical trial to treat multiple sclerosis.

For more information about this collaboration, please contact Andrew Watson, Ph.D., director of technology transfer, at or 503-494-8309.

Cyagen Biosciences to present on new rapid generation technology, July 12

Marvin Yingbin Ouyang, Ph.D., vice president of technology at Cyagen Biosciences, Inc., will present “CRISPR/Cas9 and TurboKnockout: Technologies for rapid generation of knockout/knockin mouse models,” sponsored by Cyagen Biosciences.

Tuesday, July 12
noon to 1 p.m.
OHSU Auditorium
Marquam Hill

Dr. Ouyang will review the traditional model of pronuclear injection based transgenics and ES cell homologous recombination based gene targeting, and go over the recently developed CRISPR-mediated genome editing technology, with an emphasis on the pros and cons of each technology and their applications. He will introduce TurboKnockout, the newest ES-cell based gene targeting technology which allows the generation of conditional knockout/knockin mouse models in as fast as six months. This presentation will also highlight VectorBuilder, a novel online tool which promises to revolutionize the way DNA vector cloning is done.

OHSU researchers visualize architecture of the TARP complex

Glutamate receptors are the most prevalent molecular “switches” mediating communication between nerve cells in the brain. They play keys roles in nearly all human behaviors, from learning to memory and movement, as simply a few examples.  Glutamate receptors are also the targets of a broad range of therapeutic agents, from anti-seizure medications to antidepressants.

Glutamate receptors do not function alone, however: they form complexes with other proteins called transmembrane AMPA-receptor regulatory proteins, or TARPs. These accessory proteins modulate the properties of the receptor and are made in different regions of the brain, thus giving rise to brain-region-specific receptor function. How glutamate receptors interact with TARPs has been a long-standing question.

In a Nature paper, published online on July 1, 2016, OHSU researchers from the Vollum Institute and the Department of Biomedical Engineering in the School of Medicine, describe the long sought after structure of a glutamate receptor – TARP complex, thus showing how the proteins interact with each other. The team led by Eric Gouaux, Ph.D., Yan Zhao, Ph.D., and Shanshuang Chen, Ph.D., used x-ray crystallography and single particle cryo-electron microscopy (cryo-EM) to capture images of the TARP structure. Their findings offer clues into how TARPs modulate receptor function and provide a template for receptor – TARP specific design of novel small molecules, entities that might prove useful as therapeutic agents.

Drs. Zhao and Chen, both postdoctoral researchers in the Gouaux Lab, contributed equally to the research reported in “Architecture of fully occupied GluA2 AMPA receptor–TARP complex elucidated by cryo-EM.” In addition to Eric Gouaux, Craig Yoshioka, Ph.D., from the Department of Biomedical Engineering and Isabelle Baconguis, Ph.D. from the Vollum Institute, contributed to this paper.

Shanshuang Chen is supported by an American Heart Association postdoctoral fellowship (16POST27790099).This work was supported by the NIH (Eric Gouaux, NS038631). Eric Gouaux is an investigator with the Howard Hughes Medical Institute.

2016 BIP Drug Discovery awardees announced

The Oregon Clinical & Translational Research Institute and OHSU Technology Transfer & Business Development are pleased to announce the funding of two Biomedical Innovation Program  drug discovery awards. A new track supports drug discovery platforms and early stage therapeutic technology projects, including validation of drug targets and the development of small molecules, antibodies, vaccines, or biologics. The BIP provides funds, project management, and mentorship to facilitate the development of innovative technologies at OHSU, and accelerate their translation from academia to the marketplace.

Congratulations to the 2016 BIP Drug Discovery awardees:



Penny Hogarth, M.D. –Associate Professor, Molecular & Medical Genetics: Fast-track CoACT


Xiangshu Xiao, Ph.D. – Associate Professor, Physiology & Pharmacology, Knight Cancer Institute:
Novel lamin-binding ligands for the treatment of triple negative breast cancer


“I am thrilled to see the BIP expand and meet the need of support for early-stage drug discovery research at OHSU,” says OCTRI Director David Ellison, M.D. “By prioritizing commercialization outcomes, the BIP helps position technologies such that they have the best possible chance of making it to market and improving human health.”

Detailed information on both awards, including project abstracts, can be found on the OCTRI website. For more information on other OCTRI’s other research support services, please visit:

OCTRI is supported by (UL1TR000128) from the National Center for Advancing Translational Science (NCATS) at the National Institutes of Health (NIH).

Welcome to the Research News Blog

Welcome to the Research News Blog

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

Participation Guidelines

Remember: information you share here is public; it isn't medical advice. Need advice or treatment? Contact your healthcare provider directly. Read our Terms of Use and this disclaimer for details.