Autism Genetics & Brain Development
Project led by Michael E. Greenberg
This team, bringing together the labs of Professors Michael Greenberg, Chinfei Chen, Michela Fagiolini and Christopher Walsh, aims to uncover the role of autism-linked genetic variations in brain development. Learn more about this project
One of the most consistent features of autism is its time of onset early in life, when environmental experiences have a potent impact on the refinement of neural circuits. Paying attention to that observation, these researchers will investigate the role of ASD-linked genetic variations in experience-dependent brain development—at the molecular, cellular and circuit levels.
The team will focus on ASD mutations that are poorly understood and/or newly identified. Their shared interests involve genes encoding protein complexes in the cell nucleus that control the activity of many other genes, such as chromatin regulators—as well as non-coding mutations in regions of DNA that do not encode any proteins themselves, but also powerfully regulate the activity of many genes, by controlling the accessibility of DNA to transcriptional machinery.
Mutations of interest will be explored in depth by characterizing their impact on gene activity across neurons of different types, their impact on the development of well-understood synapses in the visual system, and their impact on excitatory-inhibitory balance in the cerebral cortex overall. Human neurons and brain tissue will be studied in addition to mouse models.
Click here for a list of select publications from member labs.
Chinfei Chen, MD, PhD
Professor of Neurology, Boston Children’s Hospital and Harvard Medical School
The Chen lab studies activity- and experience-dependent plasticity during brain development. As part of the Tan-Yang Center, the lab is characterizing the role of ASD mutations in developmental refinement of neuronal networks, using electrophysiological recordings of synapses of the mouse thalamocortical circuit as a model system.
Michela Fagiolini, PhD
Associate Professor of Neurology, Boston Children’s Hospital and Harvard Medical School
The Fagiolini lab studies how neuronal networks in the cortex acquire functional properties during experience-dependent brain development. As part of the Tan-Yang Center, the lab is investigating the role of ASD mutations in this process, conducting a systematic quantification of excitatory/inhibitory network activity over key developmental time periods.
Michael E. Greenberg, PhD
Nathan Marsh Pusey Professor of Neurobiology, Harvard Medical School
The Greenberg lab studies how experience-driven neuronal activity regulates gene expression and promotes the maturation and refinement of brain circuits. As part of the Tan-Yang Center, the lab is investigating the role of chromatin regulators, often mutated in ASDs, in activity-dependent developmental processes.
Christopher A. Walsh, MD, PhD
Bullard Professor of Pediatrics and Neurology, Boston Children’s Hospital and Harvard Medical School
The Walsh lab identifies mutations and mechanisms that regulate the normal development and function of the human cerebral cortex. As part of the Tan-Yang Center, the lab is functionally characterizing the role of somatic and non-coding mutations linked to autism using human stem cell-derived neurons.
Sensory Experiences & Social Behavior
Project led by David Ginty
This team, bringing together the labs of Professors David Ginty, Bob Datta, Catherine Dulac and Lauren Orefice, seeks to understand how sensory experiences occurring early in life might shape neural circuits controlling social behavior—and what this means in the context of autism. Learn more about this project
The majority of autism research to date has focused on the brain and exploring underlying causes for three main diagnostic symptoms: difficulties with communication, challenges in social interactions, and restricted and repetitive behaviors. Although noted in Leo Kanner’s original description of autism in 1943, only recently is altered sensory reactivity considered an additional core symptom. Yet about 95% of people with ASD experience altered reactivity to sensory stimuli, and recent findings from team members have revealed that the peripheral nervous system may be playing a crucial role in ASD. Indeed, genetic mutations expressed only in peripheral sensory neurons can account for touch over-reactivity in ASD mouse models. And touch over-reactivity due to the dysfunction of peripheral sensory neurons during development contributes to altered brain development, as well as anxiety and social interaction difficulties.
Now, through multidisciplinary studies, this team aims to define the neurobiological mechanisms of affective touch as well as understand the basis of gastrointestinal dysfunction in ASD. Ultimately, these studies will identify how problems originating in the periphery lead to changes in social brain and behavior.
Click here for a list of select publications from member labs.
Sandeep Robert Datta, MD, PhD
Associate Professor of Neurobiology, Harvard Medical School
The Datta lab has established a machine learning algorithm based on motion sequencing that reveals the timescales and structure of mouse behaviors. As part of the Tan-Yang Center, the lab is using a new, specialized form of this method, called So Mo-Seq (Social Motion Sequencing) to study social interactions in ASD mouse models.
Catherine Dulac, PhD
Higgins Professor of Molecular and Cellular Biology, Harvard University
The Dulac lab studies the neuronal circuits underlying innate social behaviors in mice, from parenting and mating to aggression and defense. As part of the Tan-Yang Center, the lab is exploring how sensory signals trigger specific social behaviors—particularly, how tactile stimuli detected by the peripheral nervous system might regulate the activity of brain circuits controlling social interactions.
David Ginty, PhD
Edward R. and Anne G. Lefler Professor of Neurobiology, Harvard Medical School
The Ginty lab studies the somatosensory system and the neurobiological basis of touch perception. As part of the Tan-Yang Center, the lab is defining the neural substrates of affective touch, testing the consequences of lacking affective touch circuitry, and determining the contributions of these circuits to the cognitive and social behaviors observed in ASD mouse models.
Lauren Orefice, PhD
Assistant Professor of Genetics, Massachusetts General Hospital and Harvard Medical School
The Orefice lab studies the somatosensory circuits that mediate our sense of touch and sensations from the gastrointestinal (GI) system. As part of the Tan-Yang Center, the lab is investigating peripheral neuron function and spinal cord processing of sensory information from the skin and GI tract, how that processing is altered in ASD mouse models, and how this ultimately impacts brain development and behavior.
Click here for a list of select publications from member labs.