Science Blog Posts from Jennifer Phillips, Ph.D.

View all science posts from Jennifer Phillips, Ph.D., research biologist and frequent contributor to the USH Blog:

A plea to the Usher syndrome community: do not rely on testimonials and press releases to influence your medical treatment decisions.

If you’ve followed any of my involvement with the Usher community over the years, from blog posts to ARVO updates to speaking at our family conferences and making dorky USH Talk videos, it should come as no surprise to you that I’m a big proponent of science communication and outreach.

Jennifer Phillips, Ph.D. highlights the importance of forging "connections with people who have expertise in different areas" of Usher syndrome.

Jennifer Phillips, Ph.D." on defining “Failure”: Disclosing when things don’t work and understanding WHY is a really important, though often overlooked realm of research. Here are a couple of USH1 research stories from today’s presentations that illustrate that point.

Jennifer Phillips, Ph.D.: Several of the talks on Day 3 at ARVO 2017 delved into the biology of what, specifically, causes photoreceptor cells to die in retinitis pigmentosa patients.

Jennifer Phillips, Ph.D. recaps ARVO 2017 Day 2 with highlights on Usher syndrome type 2A research from Erwin van Wijk and colleagues at Radboud University Medical Center in the Netherlands and RP research by Neena Haider and her team at Massachusetts Eye and Ear.

Jennifer Phillips, Ph.D. shares highlights of Usher syndrome research from ARVO 2017.

In addition to the unprecedented ability to target and study disease genes, CRISPR/Cas has promising potential for disease therapy as well. There is reason to hope that this strange bacterial innovation could someday provide a cure for human diseases like Usher syndrome.

Up to this point, the focus of the presentations I’ve attended here has been on interventions designed either to correct RP at the molecular or cellular level. The progress, while promising, is also slow and complex. We’re not there yet, and the question remains for people who have RP now, what can we do in the meantime?

Part of the challenge in working out treatments for RP is that the clock is always ticking. While researchers and clinicians work like mad to figure out the mechanisms of different genetic disorders, our patients are steadily losing retinal cells.

Day 2 is in the books, and, whether by virtue of my coincidental itinerary selection or of the magnificent foresight of the ARVO Annual Meeting organizers, today’s talks and posters were the ideal ‘next level’ to the material that was presented on Day 1.

Greetings from Denver, and apologies for the long silence on this blog from me. If you were wondering whether I’d lost interest in Usher syndrome, quite the contrary! I’ve been neck-deep in some very exciting research over the past year, some of which I’ll be presenting here this week.

Gene therapy is still a relatively new development, and so far, the only USH target being delivered via viral vector in clinical trials is MYO7A (USH1B). There are a few different reasons for this, but all boil down to a numbers game.

Preventing or slowing the rate of retinal cell degeneration in the various forms of RP has been a well-covered topic at the past few ARVO meetings, and this year is no exception.

Since I've spent the past few days talking in generalities, I’ll spend today’s blog giving a brief overview on the research specifically dealing with Usher syndrome.

Another day of scientific discovery has come and gone here at ARVO. Continuing with yesterday’s inspirations from Chris Anderson’s book “Makers”, the theme of today was Crowdsourcing.

Hello once again from ARVO! I’m writing to you from the Orange County Convention Center in Orlando, having just completed the first day of the 2014 Annual Meeting.

I know that at least some of you read the post I authored last August on a newly published report on acupuncture treatment for retinitis pigmentosa. Since that time, there has been quite a bit of continued discussion in the Usher community surrounding the October publication of the study in the journal Clinical and Experimental Optometry, at which time the protocol was made available for other acupuncturists to purchase. Given this ongoing discussion, which has taken place alongside a marketing campaign for the practice where this procedure originated, it seemed like a good idea to post an update.

We Usher Coalition Bloggers are a bit of a mixed bag. Adhering to the age-old advice for authors, we all write what we know. Mark and Kate write as people who live with the diagnosis of Usher syndrome and serve as community advocates. What I know is the science of Usher syndrome, and as such, the vast majority of my posts are heavy on facts and light on personal perspectives.

Sometimes being the resident scientist on this blog is a challenging job. There are promising new developments to write up, but also stories that are more complex, controversial, or just plain worrisome. I’ve put off writing this post for a while because it’s been a tough one to process, but I sincerely believe our readers need to make informed choices about any new treatment options that might come their way, and I hope this write-up will help make that possible.

ARVO 2013 concluded two weeks ago, but there are still a few more noteworthy stories from ARVO to tell, and this is one of them.

Whew! Day 4 is in the books, and what a day it was. I saw more excellent science presentations than I can count (and a few disappointing ones, too, but that’s a story for another day). I engaged in stimulating discussions about research directions throughout the day and managed to catch sight of a few Seattle landmarks while walking and talking with a colleague before hunkering down in my quaint little hotel room to write this up.

Day 3 of the ARVO meeting was filled with a lot of presentations on retinal cell biology—nitty gritty details about how tiny molecules are transported hither and yon inside the cell, and what goes wrong if the transportation system breaks down. Mother’s milk for me, but probably not for most of our readers. There were, however, a number of poster presentations that might be of general interest here:

The talks I attended today were on the topics of photoreceptor cilia, Nanotechnology and Regenerative Medicine, and Stem Cell therapies. Afterward, I saw posters on a wide variety of studies related to retinal degeneration.

Greetings from sunny Fort Lauderdale Seattle, destination for this year’s ARVO meeting. I’m here all week, and I’ll be blogging on the very latest vision research going on around the world that has some relevance to Usher syndrome.

A couple of new stories/updates that will probably be of interest to our readers.

I am an animal lover. I make cozy little shoebox homes for the injured birds that regularly smack into our picture windows. I carry spiders, beetles, moths and most other critters who find their way into my house outside, rather than smashing them. A happy, well-fed Golden Retriever is resting her head on my lap as I type this.

Since my return to blogging with an analysis of recent peer-reviewed literature on Usher research, another paper that will probably have relevance to a lot of our blog readers has come to my attention. In contrast to those first two papers on new Usher genes, however, this one isn’t exactly a cause for celebration.

In the past couple of months, two papers have come across my desk that I immediately filed under “blog fodder”—reports of two new human genes that are linked to cases of Usher syndrome. This is exciting news indeed, not only because it tells us more about Usher, but because the techniques used to identify disease genes are becoming more powerful and effective all the time.

The bulk of the presentations I took in today were reports from clinicians treating Usher patients. I don’t get to interact with clinicians on a regular basis, so it is hugely instructive for me to get their perspective on diagnosis and monitoring of the progressive retinal degeneration seen in Usher syndrome

Here at ARVO the last events of the day are the award lectures. Each year, several of the most impacting clinicians and scientists in the international Ophthalmology and vision research community are chosen to receive various awards and deliver a plenary lecture.

Today was an 11-hour maelstrom* of really good science. Of all the great research stories I heard, there are several that will likely be of interest to our readers:

The ARVO meeting started on Sunday, but I’ve actually been here since last Thursday to attend a pre-ARVO meeting on the topic of Retina Ciliopathies. That was an intensely focused two days, indeed. I have talked about the connecting cilium of the photoreceptor quite a bit on the blog, most recently in reviewing what we know about the molecular causes of USH1.

At last year’s ARVO conference there was a presentation reporting successful animal testing for a gene therapy product called “UshStat”*. While this work has not yet appeared in a peer-reviewed publication the ARVO abstract can be found here. The poster presentation at the meeting described the use of a non-pathogenic viral vector to deliver a normal copy of the gene affected in Usher Type 1B (MYO7A) into the retina.

In preparing to write this blog post, I planned to leap right into the meat of the study, because I know that’s what you all are most keen to hear about. However, once I got into it I realized that I’d be doing our readers a disservice by cutting to the juicy center without context.

The current standard of pediatric care mandating that all newborns undergo hearing screenings has been applied successfully throughout the industrialized world. Early identification of hearing impairments gives valuable lead-time to parents and health care providers during which they can plan medical and educational interventions to improve the child's development, acquisition of language skills, and general quality of life.

In this post, I'll introduce the molecules known to be affected in Usher patients, and begin to describe what is known about their function.

Usher syndrome is a genetically recessive condition characterized by hearing impairment--usually from birth--due to defects in the sensory neurons of the inner ear, and vision loss due to retinal degeneration, which begins to occur in childhood or adolescence and progresses through several decades.

Here's my somewhat belated follow up to Mark's last post regarding the unanswered questions about Vitamin A as a potential treatment for Usher syndrome.

The last day of the ARVO meeting was short and sweet, and the very last presentation I saw before heading to the Ft. Lauderdale airport was the one I'm choosing to recap here. The talk was by Hari Jayaram of the University College London's Institute of Ophthalmology, who described a collaborative research project in which cultured human retinal cells were implanted into a rat model of retinal degeneration. At first glance it might sound like the premise of a Mad Scientist thriller, but it was actually quite a well-designed and relevant study. Here's an overview of the experimental rationale, set-up, and outcome...

Today at the ARVO meeting I saw a nice poster presentation that may add a bit more data to that story. The authors, from the same research group at U Mass that produced the original patient study published in the British Journal of Ophthalmology, now report the results of dosing mice with a severe form of RP with Valproic Acid.

Today's cool Usher science story comes from Kate McCaffrey and colleagues at Rosalind Franklin University, who are making some interesting discoveries about a new potential therapy for Usher type 1C.

Today was a 12-hour juggernaut of talks, poster presentations (mine included) and really good scientific and social conversations. While many of these situations would make great blog fodder, one series of talks really had the wow factor. This session was entitled "Optogenetics, Visual Function and Restoration".

I'm here in sunny Ft. Lauderdale attending the Association for Vision Research and Ophthalmology meeting-that's right the teeming nerd hordes are at it again.

In the summer of 2010, a small observational study of the effects of Valproic Acid was published online in the British Journal of Ophthalmology1. This study reported on seven patients with autosomal dominant retinitis pigmentosa (ADRP) who were given daily doses of a drug called (in its generic form) Valproic Acid, or VPA.

A study published in the journal Investigative Ophthalmology and Visual Science this month reports on a study that could lay the groundwork for a clinical trial at some point in the future.

I haven't been completely out of touch with the world of science, however, as I've been working long hours preparing a manuscript for submission. It's a labor of love, to be sure, combing through pages and pages of carefully laid out results, multi-panel figures, looking for opportunities to make tiny improvements and (hopefully) spotting glaring omissions before the reviewers find them.

Time passes in the research lab marked by scientific conferences, submission deadlines, and project completion. There's not much awareness of the academic calendar for those of us who don't teach regularly, but from time to time we host a new graduate student for a 12-week stint that corresponds to our academic quarter system, which tends to wake us up to the fact that we actually work at a University

To briefly summarize, there is strong experimental evidence to suggest that at least some of the time these Usher proteins physically link together to form molecular complexes that carry out some cellular functions. There are a lot of different Usher proteins involved, so understanding just the activities of those proteins has been quite challenging.

We're slowly progressing through the wealth of interesting talks at the Conference last May, and even though I didn't actually attend the Valencia meeting, I have enough familiarity with the dense molecular topics therein to give an adequate summary and their relevance to the Usher community.

Over the last 20 years or so, several studies have been conducted examining the effects of various dietary supplements on patients with progressive Retinitis Pigmentosa (RP) from a variety of causes. As a minor but important side note, these studies excluded patients with clinically diagnosed Usher type I, but did include some patients with diagnoses of Usher type 2.

So, if we agree that change needs to happen, and that we have the power to influence this happening, let's start talking about HOW it should happen.

This is a planned public debate between Mark Dunning and Jennifer Phillips, the two primary contributors to this blog. The ideas expressed in the posts during this debate will be purposely provocative and unfinished to invite a response from the other party. We hope you find the discussion valuable.

Mark began this debate by airing some grievances against the scientific and medical communities. The central charges as I read them (from my anti-hope enclave) are as follows:

Scientific and technological advances have, over the past couple of decades, brought us to the brink of some viable stem cell therapies for a number of human ailments. The human trials for most of these treatments are, as of this writing, still extremely preliminary, but the rate of progress makes this form of therapy a distinct possibility within the lifetime of nearly everyone reading this blog today.

The video below has to be one of the best things I've ever found on YouTube. I'll spare you the long boring lecture this time, but I will preface the video by saying that it features some of my scientific role models, most notably Carl Sagan.

While most of the science I've discussed on this blog so far has been fairly clinically oriented I think there's some value in spending some time getting back to the basics of the system.

The results could have an impact on developing Usher treatments in the future. The research describing the disease progression in the mouse model adds a great deal to the understanding of what might be going on at the cellular and molecular level in the retinas of human USH2A patients.

The majority of my time on this blog has been spent presenting the inner workings of the scientific process: How the research world turns, why it works, how progress is measured, etc. I've been relentless in my self-appointed mission to convey to you that, in a nutshell, science is hard to do, and easy to get wrong.

In Part I, I described the gene replacement therapy used in a pilot experiment to treat progressive retinal degeneration in LCA patients. Without rehashing the details, the major finding from this study to keep in mind is this: delivering a healthy copy of the gene via viral vector into the retinas of LCA2 patients resulted in improved vision in most of the subjects.

The research I want to share with you involves gene therapy for another retinal disease that shares some similarities with Usher syndrome.

While I'm putting the finishing touches on that opus, I just want to briefly respond to Mark's last post, specifically regarding the relative expertise and motivation of Usher researchers vs. parents, siblings, teachers, social workers, mentors, or other members of the support network surrounding an individual with Usher syndrome.

The degree to which any single finding might impact the field is largely informed by the context provided by the other data points surrounding it, which can lend support, relevance and strength to the conclusion.

In the next few posts, I'm planning to present an overview of biomedical research, and I'll begin by discussing the general flow of information from the laboratory bench to the patient.

Greetings to all, and a big thank you to Mark for inviting me to contribute to his Usher Syndrome Blog. My name is Jennifer Phillips, and I am a research biologist specializing in molecular cell biology of Usher syndrome.

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