Autism spectrum disorder (autism) is now diagnosed in approximately 1 in 36 children and is one of the fastest-growing diagnoses in the United States.

In honor of Autism Awareness Month, we highlight the research efforts performed at Mass General to better understand autism from a genetics lens and provide new discoveries and research advancements to help individuals on the spectrum achieve their goals.

In this Q&A, we spoke with Michael Talkowski, PhD, and Elise Robinson, ScD, to learn more about their ongoing research efforts and where they see autism research headed in the next couple of years.

Dr. Talkowski, director of the Center for Genomic Medicine at Mass General and Desmond and Ann Heathwood MGH Research Scholar 2015-2020, is working to understand the impact of changes to the genome structure and function in human disease. 

His research team studies the genetic causes of disorders of prenatal, neonatal, and early childhood development, particularly autism and related neurodevelopmental and psychiatric disorders.

Dr. Robinson’s research focuses on the genetic influences on  behavior and cognition. She uses genetic data to understand the biology of neurodevelopmental variation and to study differences within and between neuropsychiatric disorders.

What type of autism research takes place in the Center for Genomic Medicine and at Mass General as a whole?

Michael Talkowski:
Our work in the Center for Genomic Medicine (CGM) envisions precision medicine as a cycle that begins and ends with patients and their families. Our programs in the CGM are  largely focused on studies that attempt to map genetic variation broadly across global populations, to predict the types of genetic variants that are likely to change the function of a gene or regulatory sequence, then try to determine if individuals with autism harbor such genetic variation in their genomes.

When we find variants associated with autism, we seek to study the mechanisms by which these genome alterations cause changes in cellular biology or the developing brain that might lead to what we call phenotypes or clinical outcomes.

Our teams are therefore engaged in this genomic medicine cycle where we are sequencing the genomes of autistic individuals, interpreting genetic changes that might lead to diagnostics, and trying to understand the biological changes that we may someday target for useful treatments.

A couple of years ago, many of us in the CGM were engaged in neurodevelopmental research, but we opened a search for individuals engaged in genomic medicine, and that search led to the recruitment of Elise into the CGM, our Psychiatric and Neurodevelopmental Genetics Unit (PNGU) and the Department of Psychiatry to build a program at Mass General around the genetics of autism. She has done a remarkable job of leading entirely new discoveries in the field and bridging all of our groups studying the many diverse aspects of autism and human brain development across the CGM, Mass General, and the Broad Institute.

Elise Robinson:
Mike and I co-lead several international consortia that are studying common and rare genetic variants associated with autism and neurodevelopmental variability  Our labs work closely together and with many others who are pursuing functional genomics and mechanistic research.

Through these cross-disciplinary collaborations that are uniquely facilitated at Mass General and in a Thematic Center such as the CGM, we’re able to integrate across multiple types of genetic signals, figure out where they have similarities, where they have differences, and leverage those points of intersection to better understand biology.

What Makes Mass General a Unique Place to Conduct Autism Research?

Michael Talkowski:
I think that Mass General is one of the leading sites in the world for conducting autism research because of its unique capacity to directly facilitate interaction between the teams leading technology development and genomics research in the CGM with an incredible breadth of experts studying the developing brain and psychiatric disorders in the Departments of Neurology and Psychiatry, as well as the remarkable teams of clinicians that care for patients every day within our walls.

This is a special place that enables us to engage in the full genomic medicine cycle of autism that brings together the power of international consortia to study and model genetic variation with the unparalleled insights to be gained from the direct treatment of patients.

Elise Robinson:
It’s important to recognize the investments that Mass General has made in autism patient care and research together. In addition to the strength of research in the CGM and the Departments of Psychiatry, Neurology, and Pediatrics, the Mass General uniquely has two clinical centers focused specifically on autistic individuals and their families.

There’s the Lurie Center, which is within the Mass General Hospital for Children, and the Bressler Center in the Department of Psychiatry.

Both centers have impressive research endeavors, but they also provide exceptional and focused patient care. Mass General provides a unique environment in which clinicians, researchers, and patients can work together to better understand variability in human thinking and behavior, and help patients and families meet their goals.

What’s next in autism research?

Elise Robinson:
Over the last several years, no small part thanks to efforts organized by Mike, many genes have been associated with the probability that someone will receive an autism diagnosis.

There’s also a lot of work to be done in understanding the extent to which the genes that have been associated with autism to this point are teaching us about biology relevant to all people with autism. Some people with autism will require full time, life long care, and others will grow up to be (or already are!) extraordinarily professionally successful and entirely personally independent.

Our research needs to better integrate and understand these differences, particularly through the lens of variation in what autistic individuals and their families see as research priorities.

Michael Talkowski:
I think in the last five years or so, there has been a significant inflection, from the point where just a few years ago we had a few genes that we knew contributed to  autism, to a point now where we understand that hundreds of genes and genetic variants are associated with autism and changes in neurodevelopment.

We are now facing major challenges as we begin to understand how, when, and to what extent these genetic variants exert their effects on the developing brain. These challenges, however, will help drive us to thinking about ‘precision medicine’ in terms of the type of genetic variant an individual harbors, its biological impact in that individual, and the ideal timepoints and tissues in which we may be able to consider therapeutic intervention in autism.

We’re also on a path to take the same approach in many other developmental and neurological disorders, where we can target those genes and think about what they do.

So, I think it’s been an exciting last five years in autism research, and I think the forecast for the next five to 10 years is a much greater understanding of the biological underpinnings of autism, the neurobiological changes that occur in autism, and the genetic targets that may be amenable to therapeutic targeting.

I think Mass General and its diverse and integrated research and patient-care communities are uniquely positioned to lead the field in all of these endeavors.

About the Mass General Research Institute
Research at Massachusetts General Hospital is interwoven through more than 30 different departments, centers and institutes. Our research includes fundamental, lab-based science; clinical trials to test new drugs, devices and diagnostic tools; and community and population-based research to improve health outcomes across populations and eliminate disparities in care.
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