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: