Gene Discovery and Clinical Impact, Rare Disease Studies for Broader Medical Knowledge

Ann Nguyen:
Hi there. I'm Ann Nguyen, Senior Associate Conference Producer with Cambridge Healthtech Institute, here for a podcast for the Clinical Genomics conference at Bio-IT World Conference & Expo 2018, happening this May 15-17 in Boston, Massachusetts. Today we're speaking with Dr. Catherine Brownstein, Scientific Director of Gene Discovery with the Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School. Catherine, welcome, and thank you for being here.

Catherine Brownstein:
Thank you so much for having me.

Ann Nguyen:
Let's touch upon your gene discovery work. What determines the disease genes and conditions you study, with an eye on clinical impact?

Catherine Brownstein:
That's a great question. I work at the Manton Center for Orphan Disease Research at Boston Children's Hospital, which investigates any condition that's defined as an orphan disease, which means that it affects less than 200,000 people. I have a special interest in rare conditions that have impact on more common conditions. For example, when I was doing my PhD work, I did it on hypophosphatemic rickets, which has impacts on bone density research. Right now, I work on very early onset psychosis, which is defined as symptom onset before age 13, but that work has impact for normal onset schizophrenia and for mental health conditions overall. But I try not to focus. If something comes in that's extremely interesting, of course we're going to go all for it and investigate it to the best of our ability.

Ann Nguyen:
How does research on rare and orphan disease enhance our understanding of medicine overall?

Catherine Brownstein:
Rare and orphan diseases can sometimes be severe monogenic forms of more common diseases. For example, if a child is hearing voices at age 4, that's extremely severe and extremely unusual. We are more likely to find a structural variation in the genome or some other genetic variation that is likely to be related to the condition. In contrast, most schizophrenics present around ages 18 to 22, or early adulthood, and we may or may not be able to pinpoint the cause because it's a known multigenic disorder. And when I was looking at rickets, we identified regulators of bone density that could be interesting for pharmaceutical companies to look into. Perhaps one of them could be a target for drug development for osteoporosis or some other bone conditions that affect a large amount of people worldwide.

Ann Nguyen:
While you zoom in on rare diseases for the sake of broader knowledge, you also look broadly or globally to answer local questions, liaising between academia and industry, and partnering with clinicians with the shared goal of enhancing patient care. What do both the research and clinical sides need to contribute to the process, and what challenges still need to be ironed out?

Catherine Brownstein:
When we make these kinds of broad partnerships, it requires transparency and openness on both sides. We need to know why the research and clinical sides are there and what they're bringing to the table, and the same with industry. Are they good collaborators? At the Manton Center, we're lucky that we've been collaborating with different groups all over the world for several years now. We know how to collaborate and how to share precompetitive data, and understand that sometimes you need to show your hand in order to make discoveries. We're experienced that way. The patients, researchers, and clinicians involved in the Manton Center know that we are always going to share data, and when you sign on with us, you're agreeing to share.

When we partner with industry, I'd say the biggest barrier is understanding that we are partners, and equal partners in the collaboration. We're not contract researchers. We have to make sure our goals are aligned and, for example, that the industry partner is okay with us publishing and putting the information discoveries out there, since we want to get the information to the widest possible audience in order to help the maximum number of people.

We don't usually have problems with that though. People who are willing to partner with us usually understand that we are doing this for the greater good, and they are doing it for the same reasons. We have some fantastic partners from all over the world in industry, academia, and nonprofit, and I can honestly say I don't have a preference for who we like to work with. They are all good and have their own unique strengths.

I think the only weakness is that these new kinds of partnerships are new. Over the years we've been doing more and more with different sectors, and we just need to keep working together and get the word out there that we're open to these kind of collaborations. We're not doing as many as we need to be doing. Not yet, anyway.

Ann Nguyen:
Well, Catherine, thank you again for your thoughts.

Catherine Brownstein:
Thank you so much.

Ann Nguyen:
That was Dr. Catherine Brownstein of Boston Children's Hospital and Harvard Medical School. She'll be speaking during the Clinical Genomics track at Bio-IT World, taking place this May 15-17 in Boston.

To learn more from her, visit for registration info and enter the keycode “Podcast”.

This is Ann Nguyen. Thank you for listening.

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