Getting to Know ASF Grantees: Dr. Jill Locke

For our third post in our Getting to Know ASF Grantees blog series, we’re happy to help you get to know Dr. Jill Locke. Dr. Locke was the recipient of a 2011 postdoctoral grant from ASF, with which she studied Implementing Evidence-Based Social Skills Interventions in Public School Setting. She is also the recipient of ASF’s 2013 3-Year Early Career Award. 

What originally inspired you to begin research in your field?

I first became interested in autism when I learned that my youngest cousin was diagnosed. At the time, I didn’t know what that meant. I remember hearing stories about my cousin’s difficulty in school, but I really didn’t know much else about autism. I was intrigued and motivated to learn more. Around the same time, I was teaching preschool part-time, and three students with autism rotated through my classroom. I distinctly remember one of my students with autism, “Johnny”, was preoccupied with vacuum cleaners; he turned every toy he played with into a vacuum cleaner. The other children in my classroom quickly learned that playing with Johnny meant playing with vacuum cleaners, and sadly, Johnny was often isolated from his peers. I was concerned because I did not know how to help Johnny engage with his peers. Luckily, UCLA had a wealth of autism experts, and I had the opportunity to enroll in Ivar Lovaas’ course to learn more about how to work with children with autism.  I developed a solid understanding of behavioral principles in working with children with autism that provided a solid foundation for me, but I was surprised to discover that interventions (at that time) targeting social ability were neither common nor well tested. So, I became interested in the development and evaluation of interventions targeting social ability in children with autism. I was fortunate to work with Connie Kasari in graduate school who had a school-based project that examined the effects of two different social skills interventions on peer relationships for children with autism in included settings. It was then, I knew I found my niche.

Can you describe the work that you did in 2011 with the ASF grant?

Certainly. In this study, I modified a social skills intervention that was designed for expert clinicians to use so that it could be used by school personnel to improve the social involvement of children with autism in public schools. Traditionally, interventions that have been proven efficacious, meaning there is evidence that the intervention works in improving certain outcomes, in university or lab settings have not been successfully implemented or sustained in real-world settings such as schools. These interventions are sorely needed in community settings particularly urban public schools that have a growing number of children with autism and limited resources. I tested this modified intervention to see whether the intervention is as successful when school personnel deliver it. My hope was that by training school personnel, I would be able to increase children’s opportunities to practice social skills with their peers at school and increase their opportunities for generalization and maintenance in a cost-efficient way. I thought that once school personnel were trained that schools would have a built-in mechanism for continued support that will help many children with autism. In some ways, this was true. The school personnel in this study were able to learn the intervention and use it accurately, and we saw positive changes in children’s social engagement on the playground and social network affiliations. However, there were a number of unanticipated barriers to implementation that prevented the continued use of the program.

Can you describe what you’re doing now?

My current work builds off of my 2011 ASF grant. I am now trying to identify school-level challenges that interfere with the implementation of the intervention I modified during my postdoc (my 2011 ASF grant). I am in the process of identifying common barriers that prevent schools from using this type of intervention and devising strategies in partnership with schools to support the implementation and continued use of this intervention. Once this phase is complete, I will randomize schools to one of two conditions: 1) training school personnel in the modified intervention only; or 2) training school personnel in the modified intervention as well as working with administrators to use additional implementation strategies to support the program at the school-level. My goal is to determine if the addition of working with schools on implementation improves the sustainability of the program.

What would you like to see studied more in the field of autism research?

I think there are many avenues of autism research that need to be studied. Personally, I would really like to see more applied research that directly helps families address concerns they experience on a daily basis for adolescents and young adults. This is an area worthy of more research as many children transition out of services during that period (despite their need) and so much is unknown at this point.

Of our current grantees (other than yourself!), is there a study that you are most excited about?

I’m impressed by all of the studies that ASF is currently funding! I feel very fortunate to be among this select group of budding researchers. I think all of these studies will be important in our understanding of the brain as well as the genetic and environmental underpinnings of autism, but I am most excited about Dr. Badeaux’s research project because it has potential implications to reverse abnormalities in the brain at such a young age.

Lastly, what do you like to do when you’re not working in the field of autism research?

When I’m not working, I love to watch movies, hang out with my family and friends, cook, play with dogs, and travel to new places, so I can pretend to be a photographer!

Links to Dr. Locke’s work can be found here:

Improving Social Involvement of Children with ASD

Live Chat Transcript with Dr. Jill Locke

Getting to Know ASF Grantees: Christie Buchovecky

For the second installment this blog series, we’re excited to bring you an interview with Christie Buchovecky. Christie used her 2011 ASF grant to fund her study, Identifying Genetic Modifiers of Rett Syndrome in the Mouse. Read on to learn more about Christie, her passion for science, and where her work has led her.

What originally inspired you to begin research in your field?

My cousin was diagnosed with autism when I was in high school. That was really the first time my family or I had heard of the disorder. Always a scientist at heart, I wanted to know more – I wanted to understand how his mind worked and what the future might look like for him and for our family. It didn’t take me long to realize that the Internet was full of misinformation about ASDs (and still is, though I applaud ASF for helping to combat that!). I knew pretty early on that I wanted to improve public understanding of ASDs and help understand what causes them.

In college at the University of Miami, a number of experiences shaped my current path and my outlook on autism and science in general. The single most influential person I met at UM was my first psychology professor, whose class should have been called “How to Think Critically”. One lesson I’d like to share with everyone: The correct answer is frequently “It depends”, meaning that we live in a world of complexity, gray areas, and incomplete and imperfect information – this is something every scientist should keep in mind. Also, for about a year in college, I spent my evenings and weekends working with a non-verbal boy with autism using ABA (applied behavioral analysis) techniques. It was some of the most rewarding and emotionally draining work I’ve ever done and gave me a great deal of respect for therapists and teachers. Lastly, I had many incredible biology professors and research mentors who inspired my love of genetics and encouraged me to pursue a Ph.D.

Baylor College of Medicine, where I am currently working toward my PhD in Molecular and Human Genetics, has a very large community of researchers working on Rett Syndrome, Autism, and other ASDs. Surprisingly, it turned out to be easy for me to decide on a project and mentor; when Dr. Monica Justice described her new research project to the incoming class, I was immediately intrigued.

Can you briefly describe the work that you did with the ASF grant?

The foundation of my work started before I ever joined the lab. That intriguing research project that Dr. Justice told us about in my first weeks of graduate school: She had received funding from the Rett Syndrome Research Trust to perform a mutagenesis screen in a mouse model of Rett Syndrome (Mecp2-null mice). The goal was to find out what biological pathways can be manipulated to improve Rett Syndrome symptoms. After creating random second-site mutations in Mecp2-null mice, she was able to identify mice in which Rett Syndrome symptoms were suppressed. Only then would we identify the mutations that caused symptom suppression and the biological pathways involved. Basically, she was throwing any expectations out the window and letting the health of the mice tell her what avenues to pursue.

All of this meant that I started my thesis project with a family of mice with greatly suppressed symptoms, but no idea what biological pathway I would end up working on. I’m extremely grateful to ASF for understanding the power of this technique and taking a leap of faith with us to identify the mutated gene and understand the involvement of the related pathway. With the help of our collaborators, we identified a mutation in the cholesterol biosynthesis pathway that improved longevity and motor symptoms. Since cholesterol metabolism had never before been implicated in Rett Syndrome, we then spent a lot of time examining that pathway in the Mecp2-null mice. Ultimately, we saw changes both in the brain and the rest of the body.

The nice thing about this finding is that we already have safe and effective ways to alter cholesterol metabolism. In the time since my ASF predoctoral fellowship, we’ve gone on to treat Mecp2-null mice with statins (FDA approved drugs like Lipitor that inhibit cholesterol synthesis), hoping to mimic the effect of our genetic mutation and improve symptoms. This turned out to work quite well and we recently published the whole story in Nature Genetics. There is still a lot to learn about cholesterol metabolism in Rett Syndrome patients. We hope our work will encourage more research into the topic and eventually lead to a treatment that will help improve quality of life for these patients and their families.

Can you describe what you’re doing now?

I’m starting to see the light at the end of the PhD tunnel, so I’m trying to tie things up and begin writing my thesis. I’ve started looking at how altering cholesterol metabolism affects Rett Syndrome symptoms at a neuronal level; this is a logical progression for the project and I’ve always been intrigued by neuroscience. We’re also pursing treatment with additional compounds that alter metabolism in the Mecp2-null mice and are trying to learn more about lipid and glucose metabolism, pathways which are closely related to cholesterol.

What would you like to see studied more in the field of autism research? Do you think there are any areas that are going to be the key to answers in the field for the future?

My graduate experience has instilled in me a sharp awareness that the brain does not exist as a separate entity from the rest of the body. Therefore, I’d like to see more good science being done looking into possible systemic changes observed in ASDs. These could turn out to be metabolic differences, immune system abnormalities, GI symptoms, or something else entirely. To make matters more complicated, it will probably be different in different people – there’s a reason we talk about “autisms”, after all. For example, we know that altered cholesterol biosynthesis plays a huge role in Smith-Lemli-Optiz Syndrome, and that Prader-Willi Syndrome has an endocrine component. Furthermore, we know that treating these aspects of the disease in affected individuals can improve behavior, and it certainly improves quality of life. I anticipate there will be similar (if less pronounced) findings in what we consider non-syndromic autisms.

Part of what makes the autism research community so powerful is the diverse background of the researchers in it and the collaborative efforts they undertake. By and large, however, we are heavy on psychologists, neuroscientists and geneticists and light on physiologists and biochemists. We need to bring more of these people into the field; when we notice a trend in the data and make some incidental finding far afield of our own expertise (because we all have those pages in lab notebooks of interesting things we didn’t have the knowledge base to follow up on), we need to reach out to our colleagues in other disciplines and get them excited about autism research.

Of our 2013 grantees, is there a study that you are most excited about?

Do I have to pick just one?

The work by Dr. Aimee Badeaux and Dr. Yang Shi at Boston Children’s Hospital on the autism brain epigenome is really interesting. I can’t wait to learn more about what they’re planning and what they find out about epigenetic changes in the autistic brain. Epigenetics is a relatively new field and techniques for studying it are constantly evolving. I think this study and others like it will create one of those situations where the more you know, the more there is to learn. As a scientist, I love it when that happens – it’s like finding a whole new set of puzzles to solve!

I’m also really looking forward to seeing how the IGF-1 trial in patients with Phelan McDermid Syndrome (lead by Dr. Alexander Kolevzon at Mount Sinai) turns out. There is a parallel IGF-1 story going on in the Rett Syndrome field that I’ve been following for a while, especially given the role of insulin in metabolism (IGF-1 stands for insulin-like growth factor 1) and its relationship to our research. It’s an interesting and complicated story. Obviously, my fingers are crossed for its safety efficacy, but no matter the outcome, this study has the potential to teach us more about Phelan McDermid Syndrome in the process.

Lastly, is there anything you’d like to share about yourself that our readers may not know or expect?

I love to cook, but am completely incapable of making just a simple meal. Instead, everything is complicated traditional recipes – mostly Italian, as an homage to my heritage, but I also picked up a love of Cuban and Cajun foods in college. On Saturdays I like to hit the farmer’s market, then come home and cook for hours – usually dirtying every pot and pan in my kitchen in the process. Since I also tend to cook for an army, even though it’s just my fiancée and I, I’ve been known to bring containers full of jambalaya, minestrone, or bolognese to my other grad student friends on a whim… Of course we all know a graduate student never says no to free food. I’ve been incredibly lucky in my time here – both to have developed such wonderful friendships and to have had the opportunity to work on such a fascinating project.

Links to Christie Buchovecky’s work can be found below:

A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome

View an interview with Buchovecky on the ASF YouTube channel here

Getting to Know ASF Grantees: Dr. Matthew Maenner

In order for great science to be done, there need to be great scientists. Dr. Matthew Maenner is one of those scientists and a former ASF grantee, as well as the first spotlight in our new series Getting to Know ASF Grantees. In 2010, ASF funded his study, Phenotypic Heterogeneity and Early Identification of ASD in the United States. More information about that study can be found here. Read on to see our Q&A with Dr. Maenner and the work he does in the autism science field.

What originally inspired you to begin research in your field?

I first learned about autism when I was an undergraduate in college; I worked with children with ASD that had very challenging behaviors.  I really enjoyed spending time with the kids, but I also realized that parents frequently had to make difficult decisions regarding treatments or interventions and they usually had very little information to guide their decisions.  And I remember feeling frustrated when a family would be talked into buying into an unproven—but very expensive—therapy or treatment.  At the time, I didn’t know what epidemiology was, but I thought we should be studying large groups of people to know whether something was effective or not.

Can you describe the work that you did in 2010 with the ASF grant?

Clinical studies have shown certain behavioral “warning signs” to be useful for early ASD diagnosis, and public health campaigns focus on these behaviors to promote earlier ASD identification.  However, there was very little evidence whether these behaviors actually lead to earlier diagnosis in everyday clinical practice. Our study examined whether the behavioral symptoms indicated by research studies were associated with earlier ASD identification in community settings.

We found that children tended to be identified earlier if they were observed to have repetitive motor behaviors, inflexibility in routines, or impairments in nonverbal communication.  In contrast, children that were observed to have problems getting along with peers, holding a conversation, or had idiosyncratic speech were more likely to be identified later, compared to children without these symptoms.   The results also suggest that increasing the intensity of ASD screening practices will likely lead to increased ASD identification at both earlier and later ages if some symptoms are difficult to detect before a child reaches a certain developmental level.

Some scientists focus on clinical studies, while you are an epidemiologist. In what ways are both types of studies important?

Epidemiological studies and clinical studies can offer complementary insights into a particular question. An epidemiological study may observe an association between an exposure and ASD in the population; then, a focused clinical study could examine the hypothesized mechanism in much greater detail. The exchange of ideas can also go in the other direction—epidemiological studies can examine whether a finding from a clinical study “holds up” outside of a laboratory setting. Epidemiological studies can estimate what proportion of all ASD may be attributable to a mechanism identified in a clinical study, or it may indicate that a biological pathway is more complex than initially recognized. Evidence from both clinical and epidemiological studies help us better understand potential ASD causes and treatments, and both kinds of studies can help inform public health policy decisions.

Can you describe what you’re doing now at the CDC?

This summer, I became an Epidemic Intelligence Service (EIS) Officer, so I will be at the CDC for at least the next two years.  It’s an incredible opportunity to learn about how the broader public health system works, how decisions are made, and how to better communicate scientific or public health messages to the public.

What would you like to see studied more in the field of autism research?

I would love to see the development of more high-quality and freely-available screening/diagnostic tools for ASD.  One of the barriers to research and early ASD diagnoses—especially in low-resource settings—is the availability of free instruments and screening tools. This year I created www.disabilitymeasures.org, which we hope becomes a collaborative platform for disseminating diagnostic, screening, and research tools. Based on the reactions we’ve heard from others (like this recent article: http://www.scientificamerican.com/article.cfm?id=a-call-for-open-access-to-autism-diagnostic-tools), we think researchers want their work to be more accessible, and we want to make it easier to accomplish this.

Of our 2013 grantees, is there a study that you are most excited about?

All of the funded studies have the potential to make important contributions.  If I had to choose, I would say I am especially interested in Russell Port’s project with Dr. Roberts. When I was a postdoc at the Waisman Center last year, Dr. Roberts gave a compelling talk on electrophysiological signatures of language impairment in ASD, and I am eager to see where this work leads them.

Lastly, what do you like to do when you’re not working?

As a scientist in the early stages of my career, the line between my hobbies and professional work is quite blurred.  However, my wife grows orchids and I’ve learned a lot from helping her grow and breed them over the past few years.  The amount of diversity is incredible—it is easy to see why Charles Darwin was so interested in them!

Links to Dr. Maenner’s work can be found below:

Phenotypic Heterogeneity of ASD and Its Association with Early Identification

Dr. Maenner Speaking about “Phenotypic Heterogeneity of ASD and Its Association with Early Identification”

Association Between Behavioral Features and Gastrointestinal Problems Among Children with Autism Spectrum Disorder

Potential Effect of DSM-5 Diagnostic Criteria on ASD Prevalence Estimates

ASF Encourages American Academy of Pediatrics to Increase Resources for Wandering Prevention

By Alison Singer
President, Autism Science Foundation

 

This morning Stuart Spielman of Autism Speaks and I met with key leaders at the American Academy of Pediatrics and representatives from over 20 children’s health advocacy groups to talk about strategies for preventing wandering. A study sponsored by the Autism Science Foundation and a consortium of autism advocacy groups, and published in the journal Pediatrics, showed that 49% of children with autism attempted to wander at least once after age 4, which is four times the rate of unaffected siblings. 53 percent of those who eloped were missing long enough to cause concern. From age 8-11, 27 percent of children with ASD wandered, compared to only 1 percent of unaffected siblings.

In 2012, 25 children with autism died as a result of wandering. By way of comparison, 35 children in the U.S. died of flu and 19 died of whooping cough in 2012.  The AAP supports massive campaigns to prevent those deadly diseases, as it should. Our goal today was to encourage the AAP to increase the resources devoted to implementing and supporting wandering prevention measures as well.

Our efforts around wandering involve both prevention and recovery. Of course we want to prevent as many wandering incidents as possible from happening, so today we talked with AAP members about including information about wandering in what the AAP calls “anticipatory guidance,” which refers to the conversations doctors routinely have with parents at well-child visits to let them know what’s ahead for their children. Only 14 percent of parents of children with autism reported that they were warned about the potential for wandering by their pediatrician (Pediatrics).  We have to do better.  Parents who are aware of the potential for wandering can take precautions to ensure the environment is as safe as possible.  We also talked about providing more training and awareness materials to pediatricians so that they can share the information with their families.

On the recovery side, the group talked about working together to develop a “wandering alert” mechanism,  similar to an AMBER alert, for children with developmental disabilities, addressing the unique needs of this population, including the propensity to head toward water and the fact that our kids might not respond when called by  first responders or other searchers.  When children with autism wander, families can’t access the AMBER alert system because technically the children are not abducted.

Wandering is an issue of life and death. The data, and the newspapers, show that children with autism continue to die from wandering related incidents.  We are committed to doing all we can to reduce wandering and to protect as many children with ASD from wandering-related tragedies as possible.

 

Source:
Occurrence and Family Impact of Elopement in Children With Autism Spectrum Disorder
Connie Anderson,  J. Kiely Law, Amy Daniels, Catherine Rice, David S. Mandell, Louis Hagopian, and Paul A. Law
Pediatrics peds.2012-0762; published ahead of print October 8, 2012,doi:10.1542/peds.2012-0762