Episode 3: Voices From the Bench and the Bedside

Episode 3: Voices From the Bench and the Bedside

Jack Faris (00:04):

Hello and welcome to our podcast, PNRI Science: Rare Disease, Real Progress. I’m Jack Faris, CEO of Pacific Northwest Research Institute, and also proud father of my co-host, Anna.

Anna Faris (00:19):

That’s me, Anna Faris, actor, producer, and yes, Jack’s daughter, which means I have had a front row seat to his science enthusiasm for quite a while.

Jack Faris (00:30):

Some might call it enthusiasm. Others might say, I’ve been known to go on a few passionate tangents about how genetics can improve lives for countless people.

Anna Faris (00:40):

Well, either way, you’ve definitely made science a big part of our lives, and I love that we get to share these conversations together, Dad.

Jack Faris (00:47):

This series was recorded at PNRI’s 2025 Rare Disease Day Symposium, an amazing day where advocates, scientists, clinicians, students, and industry leaders all came together with one goal: to accelerate diagnosis, improve treatment, and advance discovery for thousands of rare diseases, and we’re sharing some of the most powerful conversations from that day.

Anna Faris (01:19)
This episode of PNRI Science: Rare Disease, Real Progress is all about the scientists and clinicians—from graduate students entering the field to experienced researchers who’ve been at it for decades. You’ll hear what drives them, what keeps them curious, and how they’re thinking differently about the future of rare disease research. Spoiler: It involves creativity, a lot of persistence, and more collaboration than you might expect.

James Bennett (01:50):

My name is James Bennett, but I go by Jimmy and I am an associate professor of pediatrics and division of genetics at University of Washington, and I also run a lab at the Seattle Children’s Research Institute within the Center for Developmental Biology and Regenerative Medicine. I’m also one of the associate directors at the Seattle Children’s Hospital Molecular Lab. I help run two different laboratories. One that’s a research laboratory focused on somatic mosaicism and vascular anomalies, and then I also help oversee clinical diagnostic lab. That’s also looking mostly at vascular anomalies. There’s a lot of rare diseases that people are looking at, and some of them arise because there’s a difference or a change in the sperm or egg that gave rise to the individual. But since humans are multicellular organisms and there’s huge amounts of cell division that happens between fertilization and birth, I’m very interested in the types of genetic variants that are rising during that period.

James Bennett (02:52):

One of the things that’s exciting about somatic mutation is that a lot of the genes that are affected, there’s already preexisting drugs for them. So we have been involved, not me directly, but Seattle Children’s and others in clinical trials looking at new therapies, repurposing preexisting drugs for developmental malformation. That’s very, very exciting. I think the other big angle for me that I’m passionate about is trying to just increase awareness that there is this huge under ascertained dark region of the, it’s not a region of the genome, but a dark type of human genetic variation that will never be found if you’ve only sequenced someone’s blood or saliva. You have to look more deeply and look at other tissues. Children with vascular malformations, it can be a routine thing to get a biopsy and get a bit of that tissue sample, but obviously some types of genetic disorders that affect, for example, the brain, it’s a little harder to come by or the heart.

James Bennett (03:47):

I am involved along with other researchers at the University of Washington and actually researchers around the country in this program called SMAHT. I think it comes out of Boston like “wicked smart,” but it’s an acronym that stands for Somatic Mutations across Human Tissues. So the goal of this large consortium project is to deeply sequence multiple different tissues from 150 people who are donating their organs at their death. One of the things that I think is important about that study is that in addition to obtaining tissue samples from their colon, from their heart, from their lung, from their brain, we’re also obtaining samples from their saliva and their blood. So we may be able to sort of make connections between the clinically accessible tissues in an individual while they’re alive and extend that to perhaps the clinically less accessible tissues in living people. The science is amazing.

James Bennett (04:43):

The clinical stuff is amazing, but the main thing I’m excited about is the fact that all these people are coming together. We have all these people from University of Washington, Seattle Children’s, Pacific Northwest Research Institute. We have a huge bench of genetics and rare disease expertise in Seattle, but I’ve rarely seen so many of these different groups or at different institutions just coming together in one place at one time. So I really am glad to see everyone sort of rowing together, and that’s always important, but right now, more than ever, one of the diagnostic tests that I’m heavily involved in is called the VANSeq test. The thing that’s exciting is that when we find a genetic change, it’s immediately clinically actionable. I mean, some of the kids who have vascular malformations are going on drugs and they’re showing benefit, so it’s giving them another weapon to help fight against their disease. It’s the right thing to do to help people out.

James Bennett (05:45):

But I’m also realistic. I understand that we as a society, we have limited resources. We have to make choices, and it’s a fair question to say, well, why would we spend a whole bunch of money on something that’s rare? I think it’s good to ask that question. It’s okay to ask that question. I would say that actually, well, first off, of course, collectively, it’s not rare, but maybe even more importantly, I think that all of the things that are discovered by studying the rare apply to the common, and I would even argue that science and medicine has almost never made significant progress without studying the rare. I would say that just as much, maybe even more progress has been made, not when we look at the people with the common forms of hypertension, but rather when we look at the very rare forms because the very rare that really shines a light on mechanisms that helps us understand the common, I think the technology had been more limiting in the, we were always required to use model organisms, and I think model organisms are crucial.

James Bennett (06:45):

They are questions that can only be asked using cells, zebrafish fruit flies, mice, et cetera. But what I’m really excited about is now a lot of the technologies, you don’t need to deal with the model organism. You just go straight to the human tissue. We’ve started to see as we go along, the differences between some of these model organisms and humans, and now because of the technological advances, we’re less required or less forced to ask these questions in animal model systems, and we can just ask them directly on human tissues. I am an optimist and the vast majority of people who are in this business of science and biomedicine and health, they’re trying to do their best and they really are trying to improve things. So if you’re interested in supporting science, get out there and support science.

Kate Helle (07:35):

My name is Kate Helle. I’m an undergraduate researcher in the Carvallo laboratory, and I am here today to obviously attend and learn from researchers in the field and then also present later this afternoon. It’s a case report on a patient with a rare complex rearrangement on their second chromosome and kind of working through how we uncovered it, how we put the structure of the rearrangement together, what we believe it could be impacting in the patient, and that genotype to phenotype connection and also other genomic technology that’s kind of really helped us put that together.

Rituparna Sinha Roy (08:09):

I’m Rituparna Sinha Roy and I work as a staff scientist at Claudia’s lab, and I’m from PNRI. I did my PhD in molecular biology, but changed from having a background of skin cancer. I have shifted to a rare disease, and right now I’m working with one of the rare diseases, which is Robinow syndrome at Claudia’s lab. So my particular work is to find the functional aspect of all these genes and the friendship variants that are causing this particular disorder in children. So I had very keen interest to work directly with patients, and during my interview with Claudia, I told her about my interest and she was like, then you must come to my lab and see what you will be working with.

Kate Helle (09:10):

I think the thing that kind of called to me a lot was genetics. I think my brain finds it as a really good way to wrap around the world and understand where health issues and changes and stuff like that may come from and where changes in your body may arise from. And I think that the genome is a huge part of that, and I think it’s a huge part of understanding a person’s lifestyle and health on a deeper level. And so I think that’s really drew me to Claudia’s lab.

Rituparna Sinha Roy (09:33):

As I’m attending this rare disease day and listening to all the panel speakers, I’m feeling more and more that we need to fill the gap between the patient and the research and the industries that are sponsoring or having the solution or therapeutics for these rare disorders or conditions. The patient family should be able to work with the researchers and finding their answers. So I feel like the gap should be closed.

Kate Helle (10:04):

Science and specifically genetic sciences can be very hard to understand without any scientific background, but I think having events like this and making science more accessible to the public and funding research that can be so powerful and impacting people’s health and helping them become more familiar with science and how they can close that gap themselves while we work on our end to close that gap with them working with patients themselves is super important. In closing that gap and working with the public,

Rituparna Sinha Roy (10:38):

I really like the panels that we are having here and specifically liking all the talks and the emotions of the family and how they are dealing with having a rare disorder child in their family or children in their family, and I’m really liking this event to have a bridge between this families and the research that all of us doing here and throughout other universities or institutions.

Kate Helle (11:11):

I was looking through the poster titles and kind of everyone who’s presenting, and we have PhD students and people who have completed their PhD and undergraduates and doctors and everything. So I think it’s just a really good variety of people here today, which is really exciting.

Rituparna Sinha Roy (11:27):

So for me, the inspiration of working in rare disorder is really looking at all these patients’ history and their stories and to really connect and finding answers. Yeah, that’s my inspiration.

Kate Helle (11:45):

I am excited about hopefully continuing to work on rare disease research working in rare disease in the name rare, you think, oh, this is something that doesn’t impact a lot of people, but I think rare disease research is so special because when you really get into the nitty gritty of it and you kind of look at these deep underlying genetic mechanisms, there’s such a key component to so many other things, and so I think even though we call it rare diseases, it’s so important to how that connects with the rest of science and so many other diseases that we hear of so much more often, and reminding ourselves to listen to experts and also learn and again, collaborate on all of that to bring it all together to a digestible level so that we can all find the importance and work together.

Larissa Robinson-Cooper (13:17):

Hi, my name is Larissa Robinson-Cooper. I’m a third year graduate student at the University of Washington presenting my research here today at Rare Disease Day, I study the intersection between epilepsy and early onset Alzheimer’s disease. It’s a little surprising to people sometimes, but yeah, people with Alzheimer’s disease compared to people who are the same age without the disease are at a greater risk of developing seizures and epilepsy, and that’s even higher pronounced for people with early onset Alzheimer’s disease. A lot of our research is done using animal models of Alzheimer’s disease, and so I do a lot of work looking at levels of certain proteins in the brain that I think might be contributing to seizures in these animals and kind of characterize what might be happening there to promote seizures. The first session today was particularly interesting to me, just hearing more from a lot of mothers of patients with rare diseases.

Larissa Robinson-Cooper (14:19):

It’s always great to hear from their perspective and hear about how they end up starting some of these great foundations to raise money for research and awareness advocacy. Unfortunately, there’s not as much funding that’s given for rare disease research as some other big things like cancer research and Alzheimer’s as a whole, even because there’s such a large impact on the patients and the families and people become very passionate and eager to talk with each other and work out these issues. I got the opportunity to go to a lot of conferences where patients and their families are also in attendance, and I feel like just being in that community is what really got me super interested and passionate about rare disease research. It’s always great to see how, of course, obviously interested in the basic science and the translational research as well. They are, especially right now with the current funding situation, it would just be really helpful for people to understand how much goes into research on not even just rare disease, but science as a whole. It takes a lot of manpower, a lot of resources. We need funding for everything there, not just researchers themselves or materials for the lab, but also the people who take care of our buildings and facilities. That’s all incorporated into research and every role counts.

Karina Schmidt (16:02):

My name’s Karina Schmidt. I’m a PhD student in the M3D program at the University of Washington, and I work in a lab that studies rare genetic skin diseases.

Jessica Ayers (16:15):

Hi, I’m Jessica Ayers. I’m also a PhD student in the same lab, which is the Simpson Lab in ISCRM (Institute for Stem Cell and Regenerative Medicine) down in South Lake Union. I focus on Hailey-Hailey Disease, a disorder in which individuals have open wounds and blistering, particularly in areas of high friction. There’s no FDA-approved treatments or curative therapies for this disease, and that really motivates our research to try to help patients that suffer from these rare skin disorders.

Karina Schmidt (16:43):

I study Epidermolysis Bullosa Simplex, which is also a blistering disease. Unfortunately, it impacts a lot of children, so leads to a not great quality of life long term, and there’s also no treatments for this disease, so it’s really important to understand what’s actually happening and trying to find some therapeutic targets to help those patients. One thing our mentor always tells us about in our research is the importance of studying something, even if there’s not robust funding for it, because these patients are still being greatly affected, and it’s important to make sure that we can do what we can to try to improve their quality of life. So learning more about what other people are doing and even learning about some of the techniques out there and other resources that other people have to offer that we could maybe implement in our own research.

Jessica Ayers (17:45):

Absolutely. Yeah, I think just to meet other people who kind of have some of the same, not struggles, but some of the same limitations is really helpful. Other people that have similar restrictions or limited patient samples, what kind of tools are they using? What information can they get from their patient population? What are things that they’re thinking about that we’re not? And that is particular to rare diseases, and the depth of information that individuals or other researchers have gotten has been pretty inspiring and certainly given me a lot to think about.

Karina Schmidt (18:27):

I’ve been really excited to see people focusing on looking at is what we can do in the lab actually going to make this better for the patients, and can we explain that to the patients and their families? Because again, that’s what it all comes down to in the end, right? Making sure that people understand how therapies can help them and hoping that they can actually help them.

Jessica Ayers (18:57):

I feel that some of the collaboration, even the ability for us to communicate virtually and share data and collaborate seems to be a lot easier than it used to be. I could see maybe in the future there could be a cohort or a collaborative group that kind of works on similar types of modeling, but for different specific diseases.

Karina Schmidt (19:19):

I really agree with Jess on this one. I think the collaborative ability, will really increase our ability to study these diseases because especially with rare diseases, we really don’t have the capacity to get many patients samples to study. Since taking biopsies on small children is not the easiest thing to do, but being able to share resources and kind of pool what different labs are capable of doing together really broadens the possibilities and our knowledge base. If somebody’s already done it or been able to show it, there’s no reason to start from square one when you can move three steps ahead.

Jessica Ayers (20:07):

I feel like this meeting too, the patient population or parents, people who are directly involved with the disease are here at the meeting, plus clinicians and researchers. Sometimes it can feel a bit siloed between people who are treating the population, people who are researching it, and then those who actually suffer from some of these diseases. And to have everyone together in one space, even the questions that are asked of the researchers has really made me think about a few things of like, okay, how do we direct our research to help the patient population, which is really all of our goals today. The people that I’ve talked to have been incredibly nice and very collaborative and really generous with their time and even suggestions about things that we could try. So it’s been a great meeting.

Anna Faris (20:56):

Thanks so much for joining my dad and me for this episode of PNRI Science: Rare Disease, Real Progress. These conversations really stuck with us, and we hope they sparked something for you, too. If you’d like to learn more about PNRI or stay connected to the work, just head to pnri.org/connect. You can sign up for updates, join an event, or even come tour the lab.

Jack Faris (21:24):

Whether you’re in the lab, in the clinic, or at home, navigating life with a loved one who has a rare disease. This work touches all of us and it moves forward because of people like you.

Anna Faris (21:37):

Because in rare disease, a diagnosis isn’t the end of the story. It’s the start of something courageous, collaborative, and hopeful.

Jack Faris (21:46):

Thanks so much for listening. We’re so glad you’re with us.

Jack Faris (21:53):

A very warm and deeply appreciative thanks to all of our sponsors and supporters who made Rare Disease Day possible. It was a smashing success, and if we make a breakthrough, it will benefit generations and generations to come. So with that, let me say particular thanks to Platinum sponsor, Trysk Print Solutions and Acadia Pharmaceuticals. Thank you also to our gold sponsors, Ultragenyx, K&L Gates, and Perkins Coie. We’re deeply grateful to our silver sponsors, Novo Nordisk, Sanofi, Ipsen Farming, Bruker Spatial Biology, SpringWorks Therapeutics, El Gaucho, and Knobbe Martens. And thank you to our bronze sponsors, Biogen, Nabsys, Dorsey and Whitney, Medlife Discoveries, and the Tall Chef. And thank you to our media sponsors, Science in Seattle and Audiotocracy. Because of this generous support, we were able to host a fantastic rare disease day scientific symposium for over 200 people. And now that information is extended to a larger audience via these podcasts, behind every sponsorship there is a person or a team of people who support the idea and go to bat for it and make it happen. So thank you to all of you.