Building a Clinical and Translational Neuroscience Program in Autism at Yale
April 11, 2022ID7690
To CiteDCA Citation Guide
- 00:00We have another great presentation ahead.
- 00:03Our next presentation is going
- 00:04to be from Jamie Mcpartland,
- 00:06who's a professor in the Child
- 00:08Study Center and who has stepped
- 00:09up to be one of our leaders of
- 00:12team science development in in NYC.
- 00:14I something that I think is going
- 00:16to be having a huge impact and and
- 00:17that we'll hear a lot more about
- 00:19it in the in the coming months.
- 00:21So Jamie, please come up.
- 00:32OK, so thanks so much for the
- 00:34opportunity to speak today.
- 00:36It's fun for me to to talk to you all today
- 00:38and have the chance to prepare this talk,
- 00:39which you'll see a little bit different.
- 00:41I'm going to really talk about me
- 00:43and why CI and how NYC is really
- 00:45been instrumental in me building
- 00:48a clinical and translational
- 00:50neuroscience program here in in autism.
- 00:52So this is I'll talk about a
- 00:53little bit really, really quickly.
- 00:55What just? Enough about autism.
- 00:57So you see why clinical
- 00:58international work is relevant,
- 00:59and then I'm going to talk about
- 01:01the stages of my research program.
- 01:03Really both in terms of scientific progress
- 01:05and how are these different stages?
- 01:07I've relied in different ways on
- 01:08why CI and benefited from my CI,
- 01:10and there's a few reflections on on why
- 01:14I think why CI worked so well for me.
- 01:18So autism, for those of you who
- 01:20don't know too much about autism,
- 01:21is a developmental condition.
- 01:23And really diagnostically,
- 01:24it's defined by impact.
- 01:25You know they're grouped in two areas.
- 01:27You could think of conceptually as three
- 01:29social communication function is impacted.
- 01:31Interests and behavioral
- 01:33flexibility are impacted,
- 01:34and sensory perception and
- 01:36response are impacted.
- 01:37And there's a few things that are
- 01:39really central to thinking about
- 01:40autism and where we stand in terms
- 01:42of translational neuroscience.
- 01:44Autism isn't a thing,
- 01:45so when we say autism,
- 01:47we're really describing probably
- 01:48lots and lots of different.
- 01:50Ideologies involving different
- 01:51mechanisms that all look kind of alike
- 01:55because that's that's how we define it.
- 01:58It's exclusively defined in terms
- 02:00of the behavioral presentation.
- 02:02Now this is challenging because even
- 02:04really good clinicians are not going
- 02:07to see everything with their eyes,
- 02:09and we have nothing biological,
- 02:10no brain scan, no blood test.
- 02:12There are genes, you know,
- 02:14single gene kind of syndromes
- 02:15that are associated with autism.
- 02:17Nothing diagnostic that we can use.
- 02:19Nothing that we can use to pick a treatment.
- 02:21Nothing that we can use to measure
- 02:23whether treatment is engaged to
- 02:24target nothing that we can use to
- 02:26determine whether the treatment has
- 02:27worked other than a clinician and
- 02:29appearance judgment of the behavior.
- 02:32That, I think is a limitation,
- 02:35and that's really the work that
- 02:36I do in my lab,
- 02:37so I we I didn't say I'm a
- 02:39clinical psychologist by training.
- 02:40I'm a, you know,
- 02:41my clinical focus is really on the
- 02:43diagnosis and assessment of autism.
- 02:45Scientifically,
- 02:45I'm a cognitive neuroscientist,
- 02:47so I study the brain in the in the
- 02:50context in which it's it's functioning
- 02:51right and living breathing human beings.
- 02:53Usually getting an EEG and the
- 02:55goal of our work is to create
- 02:57biomarkers so more objective,
- 02:59hopefully more sensitive ways that we
- 03:01can understand autism and overcome.
- 03:03Some of the limitations that I've described,
- 03:05so I want to talk now a little bit
- 03:07about how things got started for me.
- 03:09You can't see my title slides,
- 03:10but I think that's as launching at Yale.
- 03:12And so I came here in 2004 for
- 03:15my clinical internship as a as
- 03:17a child clinical psychologist.
- 03:20And at that time in 2004 I had published
- 03:22a paper that I was really excited about
- 03:24work that I had done in Graduate School.
- 03:26Looking at an EEG electroencephalogram
- 03:29based biomarker for autism,
- 03:31one called the N 170 that tells
- 03:32us about how the brain.
- 03:34Processes faces,
- 03:35which is really relevant to autism
- 03:37because face processing is so
- 03:39central to social interaction,
- 03:40that's something that's affected in autism,
- 03:42and so came here really excited about this,
- 03:44but my position was as a clinical intern
- 03:47and then as a clinical postdoc and then
- 03:50as a clinical associate research scientist.
- 03:54And so I was spending a lot of time
- 03:56doing work that I very much enjoyed with
- 03:58children and with adults with autism,
- 04:00but I really wasn't in a position
- 04:02to be making much progress.
- 04:04In terms of research,
- 04:05didn't have a lab,
- 04:06I mean I did have a lab
- 04:07in terms of the people.
- 04:08I didn't have a lab lab in terms
- 04:09of the equipment that could use
- 04:11to collect the data that I that I
- 04:12study and I didn't have any kind of
- 04:14startup to acquire these kinds of
- 04:16things and so that was the 1st place
- 04:19where YC I was really instrumental,
- 04:22kind of starting a lab in 2006 YC
- 04:25I offered the first cohort of CSA
- 04:29scholars and I applied and a study
- 04:32really to to follow up on those.
- 04:34Initial findings about this is N 170
- 04:37to study its functional specificity
- 04:39and I was awarded a CTS a scholarship
- 04:42from ICI and that really changed a
- 04:44lot of things and and provided me
- 04:47an opportunity to be involved with
- 04:50research for real so it one it.
- 04:52It gave me protected time so days when
- 04:55I didn't actually have to be in clinic,
- 04:57earning my keep where I could be doing
- 04:59other things like analyzing data,
- 05:01writing papers, writing Gantz, grants it.
- 05:04They gave me funding, you know,
- 05:07it gave me some research funding that
- 05:09I could use in ways that I chose to
- 05:11get things started and that was really
- 05:14helpful for me because it's expensive
- 05:16and it's expensive to start an EEG
- 05:19research program and it you know
- 05:21the YC fund certainly weren't able.
- 05:23You weren't sufficient for me
- 05:24to go out and buy an EEG lab,
- 05:26but what they did do is let me
- 05:28partner with with people who
- 05:29were doing this kind of work.
- 05:30Linda Mays,
- 05:31who's now a mentor and longtime collaborator
- 05:33and the chair of my department.
- 05:35Was engaged in the egg research
- 05:37and this let me buy in to to get
- 05:39part of the time of people who
- 05:41knew how to collect EEG data.
- 05:43So it wasn't just me.
- 05:44Let me buy some EEG Nets so that
- 05:46I could contribute to the lab and
- 05:49have the the kind of tools that
- 05:51I needed to collect data it in
- 05:53the virtue of doing these things.
- 05:55It also set me up to have mentorship so the
- 05:57the white CI grant formally had mentorship.
- 05:59So you know, many people through the
- 06:01medical school that connected me to.
- 06:03But then also, you know,
- 06:04in the course of this relationship.
- 06:06Getting mentors kind of on the job.
- 06:08People who knew what they were doing.
- 06:09And then lastly,
- 06:10one of the things a less formal benefit
- 06:13from my perspective was becoming a
- 06:15member of a scientific community
- 06:17in terms of why CI, because I,
- 06:19I think I really enjoy being a
- 06:22part of the clinical community,
- 06:24but that's different and this is an
- 06:26opportunity to be a part of like minded
- 06:28scientists studying lots of different things,
- 06:30but I'm trying to do this trying
- 06:32to start a research program while
- 06:34also being a clinician.
- 06:36The.
- 06:36That that that grant let me
- 06:39collect data that I could then
- 06:41leverage to to write other grips,
- 06:44and that was really effective.
- 06:45So within a short period of time I
- 06:47was able to get funding to continue
- 06:49this work from NARSAD from foundations
- 06:51like NARSAD and Simons Foundation
- 06:52from NIMH like an RO three and and
- 06:55a K 23 and that really set me up to
- 06:59to launch an earnest and so in 2009.
- 07:01Then I would move from associate
- 07:03research scientist to professor
- 07:04was really able to to assist a
- 07:06professor and was really able to.
- 07:08To Ghetto Lab going and in
- 07:10the years it's followed,
- 07:11I've really actually I've done other
- 07:12things but but one of the things I've
- 07:14continued to do is interrogate the in 170,
- 07:16which is the slide title you're not seeing,
- 07:18and we've learned a lot about it.
- 07:20We've learned that it's
- 07:21developmentally relevant,
- 07:22something that's very challenging,
- 07:23and autism is a person has
- 07:25autism when they're three,
- 07:26and they have autism when they're 60.
- 07:28And when you're studying the brain,
- 07:30things look really different,
- 07:31and so we're actually.
- 07:32We've actually learned that this
- 07:34marker is as interesting in, you know,
- 07:36three or four year olds as it is.
- 07:38And 40 year olds.
- 07:39We've learned about how this brain
- 07:41marker relates to the clinical phenotype
- 07:44that we can see relationships between.
- 07:47How fast a person's brain responds to faces,
- 07:50measured with EG.
- 07:51And things like how good they
- 07:52are actually recognizing faces or
- 07:54the severity of autism symptoms
- 07:56or things like that.
- 07:57We've understood,
- 07:58you know,
- 07:58when you take a A6 year old and
- 08:01you put them in an EEG lab,
- 08:02they're going to do lots and
- 08:04lots and lots of things.
- 08:05A small portion of which are
- 08:06exactly what you want them to do.
- 08:08And so we've learned how robust
- 08:10our assays are to all the different
- 08:13kinds of things that could happen
- 08:15when you try to record data from
- 08:18a a human being doing the things
- 08:20that they choose to do,
- 08:21and they're pretty reliable.
- 08:22And then most recently,
- 08:24excitingly and preliminarily
- 08:25we've got in the sense that this
- 08:28marker also tracks changes so as
- 08:30children undergo treatment and
- 08:32their social behavior changes
- 08:33to become more engaged.
- 08:35For example, we actually see this
- 08:37response that's less efficient.
- 08:38They're slower in people with autism,
- 08:40get faster, get more.
- 08:42Like typically developing kids,
- 08:43and then lastly, we've we've.
- 08:46We've branched out.
- 08:46I mean, I don't think that the
- 08:48and 170 is something that is
- 08:49uniquely relevant to autism,
- 08:50and so we've used, you know,
- 08:51often collaborations through CI
- 08:53to study and other conditions
- 08:55like schizophrenia or anxiety.
- 08:56And then we've we've done work to try
- 08:58to figure out if the things that we've done,
- 09:00and then other that other people are done,
- 09:01are are true in general,
- 09:03like conducting men analysis, and they are.
- 09:05And so this is a lot of the work that
- 09:07we've done in the course of doing this.
- 09:08It's been there's been new ways
- 09:10for me to benefit from and,
- 09:12and increasingly,
- 09:13I hope to benefit why CI and for example,
- 09:17in you know, I am preparing this talk.
- 09:19I was looking through and I
- 09:20wasn't even aware of the time,
- 09:22but the collaborators involved in this line
- 09:24of research or other lines of research.
- 09:26In the lab.
- 09:27There's actually 11 different
- 09:29subsequent CTA TSA scholars that
- 09:31have been involved in our work,
- 09:34which is really great,
- 09:35and I think exemplifies the
- 09:37idea of community.
- 09:39So having got a lab going this,
- 09:43this slide is really about kind
- 09:44of expanding scope beyond Yale,
- 09:46and so in 2014,
- 09:47NIH put out a request for applications for
- 09:50development of a biomarkers consortium,
- 09:54and this was a.
- 09:55This is a big deal in our field because
- 09:58it was a a magnitude of investment
- 10:00in in research that NIH had not made
- 10:03an autism in a single award like this before,
- 10:06and it was really,
- 10:08really scientifically well suited.
- 10:10To what I do,
- 10:10it was about EEG and it was about using
- 10:13eye tracking to monitor visual attention.
- 10:15So scientifically perfectly suited,
- 10:18conceptually, logistically,
- 10:19way, way, way over my head.
- 10:22I was an assistant professor
- 10:24at the time and YC I.
- 10:26The first thing I did was reach
- 10:28out to Tisha and to Bob Sherwin,
- 10:30who was the head of C at the time and say,
- 10:32like, hey,
- 10:32this is like I got to apply for this.
- 10:35How can you? Where do I start?
- 10:38And I got a lot of help.
- 10:40With crafting a successful application,
- 10:41you know both advice about who to
- 10:44talk to advice about you know?
- 10:46What should administrative core look like.
- 10:48They don't teach you that in
- 10:50clinical psychology Graduate School
- 10:51and then also examples, right?
- 10:52There's there are other people
- 10:54that yell who have written grants
- 10:55like this and and getting you know,
- 10:57tips about who I could talk to,
- 10:58who might be willing to share an
- 11:00example of a cephalopod successful
- 11:01application, successful core,
- 11:02and it it worked. The application was funded.
- 11:06We started the Autism Biomarkers
- 11:08Consortium for clinical trials,
- 11:09and then the next challenge.
- 11:10It really was like wow.
- 11:12We got the grant.
- 11:13Now we've got to do this
- 11:14and then why CI was even more helpful.
- 11:16I mean really,
- 11:17I show this org this org chart.
- 11:19Not because I expect you to be
- 11:20able to see the fine print or
- 11:21understand it or anything like that,
- 11:22just to to give an impression
- 11:24of what a complex and intricate
- 11:27infrastructure supports this consortium.
- 11:29And so there are things that I did not,
- 11:31you know, not know how to do.
- 11:33I didn't know what they were starting
- 11:35this consortium and things like you know
- 11:37how to run a data coordinating core,
- 11:39how to cite, monitor what is good.
- 11:41Clinical practice and how to train
- 11:43sites in good clinical practice.
- 11:45We why CI help with recruitment.
- 11:47We've heard about kind of outreach
- 11:49for the diverse populations.
- 11:51They help with that and many other
- 11:53things developing our web presence,
- 11:54managing the biospecimens that we
- 11:56collected providing regulatory regulatory
- 11:58support for month multicenter study,
- 12:00and then really,
- 12:01I've worked extremely closely.
- 12:03I continue to work extremely closely with
- 12:06YCS project management division really to
- 12:09to to oversee the conduct of this study.
- 12:12And it's been extremely successful
- 12:14in this model I've found.
- 12:17Extremely applicable to this kind
- 12:20of research and that as as one Pi.
- 12:24Who has you know my expertise
- 12:27is autism and neuroscience.
- 12:30How am I going to pick the person and
- 12:32train them to do some of these things?
- 12:33I couldn't,
- 12:34and so being able to access a group
- 12:36that has this expertise built in was
- 12:38that the only way that this kind of
- 12:40thing could be successful for me at least?
- 12:42And so and it was successful in this slide,
- 12:45is entitled Changing Practice.
- 12:46And so we we succeeded in this
- 12:48first project period of running.
- 12:50You know,
- 12:51really what I I think is objectively
- 12:54the most rigorous and ambitious
- 12:56neuroscience study conducted in autism.
- 12:59We saw 450 children.
- 13:00Across four years,
- 13:01that's hard to do when you're
- 13:03talking about children with autism.
- 13:04That was over 1000.
- 13:06Visits across these five sites.
- 13:09The the data that we produced was
- 13:11consistent with our hypothesis.
- 13:13This N 170 marker was one of the that
- 13:16I've described was one of the markers
- 13:18that we studied in the ABC TV and
- 13:20as a result of the data that we got
- 13:22in this large and rigorous study,
- 13:23we were able to submit a letter of
- 13:25intent to the FDA to their biomarker
- 13:28qualification program that was accepted.
- 13:30And so this this marker that you
- 13:32know the first coming out of the
- 13:34CTS a grant from my CI is now the
- 13:37first marker for autism first.
- 13:39Marker for any psychiatric condition
- 13:40to make it to this stage in the day's
- 13:43biomorphic qualification program.
- 13:45And that's an important milestone.
- 13:46But those of you,
- 13:48many of you may recognize that
- 13:50is not a qualified biomarker.
- 13:52Most of the work remains to be
- 13:54done and why CSI continues to be
- 13:56instrumental in this work in our
- 13:58ongoing interactions with the FDA.
- 14:01This is one of my favorite pictures
- 14:02to show in
- 14:02my research, because this is the
- 14:04Tiffany Farchione who's the director
- 14:06of the psychiatry division at the FDA.
- 14:08And if you can, this is her.
- 14:09Talking at a conference in Denmark
- 14:11and you can see our acceptance
- 14:13letter on her slide, right?
- 14:14And so this is when when you're the
- 14:17first biomarker to be evaluated for
- 14:19the FDA for a psychiatric condition.
- 14:21There's no precedent,
- 14:22and so we're really to me in this very,
- 14:24very exciting space of working with
- 14:26the FDA to figure out what this like.
- 14:29How do you validate a biomarker for
- 14:32condition that exists purely behaviorally,
- 14:34right? I mean,
- 14:35that's a if any of you know the answer,
- 14:36please interrupt me and tell me
- 14:38and you'll save us a lot of time.
- 14:39But that's we're doing really
- 14:40exciting work now.
- 14:41In that area.
- 14:42The this grant the United team was
- 14:44reviewed and renewed in July 2020.
- 14:46And again we're using the same model,
- 14:49rely extremely heavily on my CI,
- 14:51and we continue to experience
- 14:53the same success, you know,
- 14:54reflecting again on the bidirectionality
- 14:56of this relationship.
- 14:58I hope I hope my PC,
- 15:00I would see it this way,
- 15:01but I think now I'm in a position
- 15:03to contribute back more,
- 15:05both in terms of you know,
- 15:06the things that I benefited from now.
- 15:09I'll get an email.
- 15:10Tisha and I'll meet with someone
- 15:12who's trying to write a grant like
- 15:13this or or could use an example of
- 15:16administrative core and help in that way,
- 15:17and then also,
- 15:18as John mentioned,
- 15:19I'm now Co directing the team
- 15:21science program with within NYC I,
- 15:23which is exciting to me because it's more,
- 15:25you know,
- 15:26an opportunity to really,
- 15:27hopefully institutionalized and create
- 15:29an infrastructure to help others
- 15:32apply these kinds of team science
- 15:34principles that we've used in the ACT.
- 15:37So just a few reflections on
- 15:38why I think why CI has worked.
- 15:40As well, it's such a good fit.
- 15:41Ways that I've thought about it
- 15:42that that I I would encourage other
- 15:44investigations to think about that one.
- 15:46I mean, this is, you know,
- 15:48this was their choice, not mine.
- 15:50But you know, being involved,
- 15:51these kinds of programs like
- 15:53the scholars really you know you
- 15:55acculturate into the scientific
- 15:57community at Yale in a way that
- 15:59has been really helpful to me.
- 16:01I think that it. It gave me a foundation.
- 16:03The community to start with.
- 16:05I was really proactive, so there's why CI.
- 16:09It's a really, really tall.
- 16:11In order to provide a clinical
- 16:13infrastructure,
- 16:13you know there are think about the
- 16:15four different talks you've heard
- 16:16today and the content of that science.
- 16:18How could one group support all
- 16:20those different kinds of research?
- 16:22That's a really, really challenging task,
- 16:24and to do it,
- 16:25there's going to be so many
- 16:26options like it's going to,
- 16:27you know there's going to be many,
- 16:29many, many options,
- 16:30and so one of the things that I
- 16:32did was really aggressively go
- 16:33to all the YMCA
- 16:34events to try to learn about all the things,
- 16:36and that was really helpful for me
- 16:38because it is the complex landscape.
- 16:41I was never. As I mentioned,
- 16:44the first thing I did when I
- 16:45got the grant was called YC I.
- 16:46You know that has been not being afraid
- 16:49to own my ignorance and in the course
- 16:51of trying to understand the complex
- 16:54landscape has been really helpful and
- 16:56I think this is a great example of it.
- 16:58There are are many,
- 16:59many people who will help you
- 17:01understand what why CI has to offer,
- 17:02but you can't.
- 17:03You can't really expect that you can
- 17:05just look at a website and understand
- 17:07everything about something so complex.
- 17:08Don't be afraid to ask and network.
- 17:11Go to these,
- 17:11go to the scholar happy hours,
- 17:13talk to people you know you're
- 17:15about to hear a a talk from.
- 17:17Marcella Marcella was in the cohort.
- 17:19Marcella gave me really helpful
- 17:21advice when I was writing this
- 17:22consortium and so getting to know
- 17:24these people was really useful.
- 17:25And then the last thing I would
- 17:27say is is conceptualizing.
- 17:29You know,
- 17:29for me it was helpful to think
- 17:30of why CI as a community again
- 17:32for something this complex is
- 17:33not like going to the mall right?
- 17:35There's not a GCP store and I go in,
- 17:38I pick up my GCP and then I walk
- 17:39next door and I do these things.
- 17:41It's a community, the the knowledge is there,
- 17:44but I think it's unrealistic
- 17:45to think that you're.
- 17:46It's like going to the white pages
- 17:47and you call the right number.
- 17:48I think it's going to be.
- 17:49You think about it as a community
- 17:51of people and you get to know that
- 17:53community and the benefits and the
- 17:55expertise that you need are there.
- 17:57And and I think that's it.
- 17:58What you can't see the top of this
- 18:00slide is that it says gratitude and
- 18:02so you know for a guy who lived here
- 18:052004 in 2004 and was doing nothing but
- 18:08IQ tests and diagnostics to have the.
- 18:11Nice to talk to you about the work that
- 18:13I'm doing to run a national consortium to,
- 18:15to develop biomarkers and in
- 18:17coordination with the FDA is is,
- 18:19you know, is it is not to be cliche,
- 18:21but it's a dream come true and so
- 18:23much gratitude to NYC for the work and
- 18:25and all the people in the lab and the
- 18:27consortium actually do these labors.
- 18:28Thank you.