{LIFE SCIENCES}

A New Era of Autism Research

A gift from Lisa Yang and Hock Tan MBA ’79 brings scientists closer to deciphering the mysteries of autism spectrum disorder

Microscopic view of cells

A New Era of Autism Research

{LIFE SCIENCES}
December 13, 2020

For Lisa Yang, raising two children, now adults, with autism spectrum disorder (ASD) has been a decades-long journey that has changed her life and priorities. As her children have grown, so too have her concerns for their future, particularly for her son who has more pronounced needs. She worries what will happen to them when she’s no longer able to advocate for their well-being and the caliber of her son’s care. Recognizing that millions of ASD families around the world are facing similar challenges, Yang has devoted much of her time to mental health advocacy and her philanthropy to autism research.

“The search to understand the nature of this disorder is dismally underfunded. I want to help move the needle,” she says. “I want people with autism to be recognized, and accepted, for their unique talents and differences, as individuals and in the workplace. I hope that through research we can discover real-world therapies that improve quality of life for those who most need help.”

With a gift of $20 million, Yang and Hock Tan MBA ’79 launched the Hock E. Tan and K. Lisa Yang Center for Autism Research at Harvard University, complementing their past giving to establish an autism research center of the same name at the McGovern Institute for Brain Research at MIT. The two institutions share a common scientific advisory board and will hold symposia to facilitate collaboration toward a shared goal: understanding the neurobiological basis of autism and related disorders, explaining the condition’s behavior and evolution, and translating those insights into novel approaches to treat its symptoms.

“I want people with autism to be recognized, and accepted, for their unique talents and differences, as individuals and in the workplace. I hope that through research we can discover real-world therapies that improve quality of life for those who most need help.”

— LISA YANG

“We are excited and hopeful that these sibling centers at Harvard and MIT—two powerhouses of biomedical research—will continue to collaborate in a synergistic way and bring about critical new insights to our understanding of autism,” says Yang, who made an additional gift to establish the Y. Eva Tan Postdoctoral Fellowship within the center at Harvard.

A University-wide effort led by Harvard Medical School (HMS) and housed within the Harvard Brain Science Initiative (HBI), the newly established Tan-Yang Center draws upon the diverse expertise of basic, translational, and clinical scientists across the entire Harvard ecosystem—uniting researchers and clinicians from HMS and its affiliated hospitals, the Faculty of Arts and Sciences, the Harvard T.H. Chan School of Public Health, and the Harvard John A. Paulson School of Engineering and Applied Sciences.

“There is an urgent need to understand the fundamental biology of autism,” says Michael Greenberg, HBI co-director, Nathan Marsh Pusey Professor of Neurobiology, chair of the Department of Neurobiology in the Blavatnik Institute at HMS, and the Tan-Yang Center’s inaugural faculty leader. “I strongly believe that the multidisciplinary expertise convened by this center will propel us into a new era of autism research, enhancing our understanding of the condition and yielding critical new insights into its causes. This generous gift will be transformative for the field.”

An Inflection Point For Neuroscience

According to 2020 studies by the Centers for Disease Control and Prevention, about 1 in 45 adults and 1 in 54 children in the United States have an ASD, a constellation of neurodevelopmental conditions that typically emerge in the first few years of life. These disorders—marked by a cluster of symptoms including communication difficulties, impaired social interactions, and restricted and repetitive behaviors—are believed to arise from the complex interplay between genes and environment, yet autism’s biological roots remain largely a mystery.

Two of the center’s initial areas of inquiry seek to address these critical gaps in knowledge. Working in groups of four laboratories each, one team of researchers is focusing on genetic variations linked to autism and their impact on brain development, while another team is examining the sensory experiences that shape social behaviors relevant to autism.

With Yang and Tan’s support, Harvard researchers are poised to make important advances in tackling this “dauntingly complex” disorder, says George Q. Daley AB ’82, MD ’91, dean of HMS and Caroline Shields Walker Professor of Medicine. For example, a recent study led by neurobiologists and geneticists at the center has identified the molecular variations that give rise to heightened touch sensitivity in people with ASDs—findings that could help pave the way toward possible treatments for the condition.

“Neuroscience has reached a unique inflection point,” Daley says. “Medical history has taught us that truly transformative therapies flow only from a clear understanding of the fundamental biology that underlies a condition. This gift will allow our researchers to generate critical insights about autism and related disorders.”

“I strongly believe that the multidisciplinary expertise convened by this center will propel us into a new era of autism research, enhancing our understanding of the condition and yielding critical new insights into its causes.”

— MICHAEL GREENBERG, TAN-YANG CENTER FACULTY LEADE

A Team Approach

Autism Genetics And Brain Development

The Tan-Yang Center’s Autism Genetics and Brain Development team aims to uncover the role of ASD-linked genetic variations in brain development at the molecular, cellular, and circuit levels during critical windows in the first two years of life, which could help illuminate how experiences modulate brain development in individuals with an ASD. Here are brief summaries of the labs’ work as part of the Tan-Yang Center:

  • Led by Michael Greenberg, Nathan Marsh Pusey Professor of Neurobiology, the Greenberg lab studies how experience-driven neuronal activity regulates gene expression and promotes the maturation and refinement of brain circuits. The lab is investigating the role of chromatin regulators, often mutated in ASDs, in activity-dependent developmental processes.
  • The Chen lab—led by professor of neurology Chinfei Chen MD ’87, PhD ’91—studies activity- and experience-dependent plasticity during brain development. The lab is characterizing the role of ASD mutations in the developmental refinement of neuronal networks, using electrophysiological recordings of synapses of the mouse thalamocortical circuit as a model system.
  • Led by associate professor of neurology Michela Fagiolini, the Fagiolini lab studies how neuronal networks in the cortex acquire functional properties during experience-dependent brain development. 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.
  • The Walsh lab—led by Christopher Walsh, Bullard Professor of Pediatrics and Neurology—identifies mutations and mechanisms that regulate the normal development and function of the human cerebral cortex. The lab is functionally characterizing the role of somatic and non-coding mutations linked to autism using human stem cell–derived neurons.

Sensory Experiences And Social Behavior

The center’s Sensory Experiences and Social Behavior team 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, including dysfunction of the peripheral nervous system and the gastrointestinal system. Here are brief summaries of the labs’ work as part of the Tan-Yang Center:

  • The Ginty lab—led by David Ginty, Edward R. and Anne G. Lefler Professor of Neurobiology—studies the somatosensory system and the neurobiological basis of touch perception. 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.
  • Led by associate professor of neurobiology Sandeep “Bob” Datta MD ’97, PhD ’04, the Datta lab has established a machine learning algorithm based on motion sequencing that reveals the timescales and structure of mouse behaviors. 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.
  • The Dulac lab—led by Catherine Dulac, Higgins Professor of Molecular and Cellular Biology—studies the neuronal circuits underlying innate social behaviors in mice, from parenting and mating to aggression and defense. 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.
  • Led by assistant professor of genetics Lauren Orefice, the Orefice lab studies the somatosensory circuits that mediate our sense of touch and sensations from the gastrointestinal (GI) system. 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.

Autism Spectrum Disorder: By the Numbers

Blue circle that reads "1 in 54"

In 2016, approximately 1 in 54 children—including 1 in 34 boys—in the U.S. were diagnosed with an ASD.

Red circle that reads 2/3

Nearly two-thirds of children with autism ages 6–15 have been bullied.

Green circle that reads 5.4 Million

About 5.4 million adults—or 1 in 45 people age 18 or older—in the U.S. have an ASD.

Purple circle that reads 31%

Thirty-one percent of children with an ASD have an intellectual disability with significant challenges in daily function; 25 percent are in the borderline range.

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