News The latest developments in autism research.
Profiles Portraits of scientists who are making a mark on autism research.
Toolbox Emerging tools and techniques that may advance autism research.
Spotted A roundup of autism papers and media mentions you may have missed.
Opinion Conversations on the science of autism research.
Viewpoint Expert opinions on trends and controversies in autism research.
Columnists Dispatches from experts on various facets of autism.
Crosstalk Debates and conversations about timely topics in autism.
Reviews Exploring the intersection of autism and the arts.
Q&A Conversations with experts about noteworthy topics in autism.
Deep Dive In-depth analysis of important topics in autism.
Special Reports Curated collections of articles on special topics in autism.
Webinars Presentations by leading experts on their latest research.
News / Profiles

Wendy Chung: Genetic sleuth is advocate for families

by  /  21 July 2011

Triple threat: Colleagues say that Wendy Chung combines strengths in teaching, research and patient care with a finely tuned ethical sensibility.

A few months ago, a young woman walked into Wendy Chung‘s office with a notebook and a flash drive. She said, “Here’s my medical history, here’s my genome, now you figure out what caused all this.”

This is exactly the kind of challenge that Chung relishes. A skilled genetic detective, she is adept at tracing an individual’s symptoms to a particular genetic anomaly, teasing out its molecular ramifications and identifying the associated syndrome.

According to those who know her well, that analytical bent is accompanied by a rare sensitivity.

“I’ve known a lot of brilliant doctors and though she’s at the top of the brilliance list, she also has a humanistic philosophy that animates everything she does,” says Hamilton Cain, the father of one of Chung’s patients. “She’s not only thinking on all cylinders, but also feeling on all cylinders. She really connects with patients and their stories and their lives.”

Chung, who began her research career studying diabetes and obesity, is director of the clinical genetics program at Columbia University Medical Center in New York as well as the university’s fellowship program in clinical and molecular genetics. Two years ago, she moved into the autism field, accepting an invitation to serve as the principal investigator of the Simons Variation in Individuals Project (VIP), launched by the Simons Foundation, SFARI.org’s parent organization. The project aims to identify and study individuals with an autism-associated deletion or duplication on chromosome 16p11.2.

Chung also teaches many core medical courses at Columbia. Her talent for teaching and mentorship has won her the prestigious Presidential Teaching Award and other prizes. She is what an earlier generation of researchers called “a triple threat” — skilled clinician, ambitious researcher and gifted teacher, says Rudolph Leibel, head of the division of molecular genetics in the department of pediatrics at Columbia University Medical Center.

“She’s certainly one of the brightest of her generation of physician-scientists,” says Leibel, who was Chung’s doctoral advisor at Rockefeller University in New York before both moved to Columbia. “In many ways, she is the poster child for physician-scientists.”

Heart problems:

Chung began her career as a basic scientist. “I was a classic academic scientist: Lab-based, cloning genes, looking for very rare pathologies,” she says. “It was very abstract but it was what my mentor had done and what I thought a successful scientist should do.”

A family tragedy led her to change her plans. Very late in pregnancy, Chung miscarried for reasons that remain a medical mystery. Chung, who has two surviving sons, says, “As that kind of experience often does, it totally changed my life.”

She says she began to wonder what she would leave behind if she were to die the next day. “I realized that I would be very disappointed if, at the end of my life, all people would say is that I had published a certain number of papers,” she says. “I wanted to make sure that what I do is making a difference in patients’ lives.”

Her goal became making discoveries that would have a direct application to human disease. Leibel says he believes that transformation would have occurred in any event, although the tragedy may have sped it up.

Chung’s substantial gifts were evident early in her career, when she was a postdoctoral researcher working in his lab at Rockefeller University, Leibel recalls.

While working on her thesis project, for example, Chung made a discovery that would have slipped by many experienced researchers, he says. She noticed that one of the animals in a diabetes study had an unusual gait, and set out to determine whether a mutation in the colony had led to the peculiar trait. She did this on her own, taking videos of the animals and working them up carefully.

Ultimately, she cloned a gene from the animal that affects conductance in the heart and can lead to lethal arrhythmias. “That kind of thing has been repeated many times over in her career,” Leibel says. “She has a good sense of what is worth pursuing.”

At Columbia, Chung is involved in a broad range of research projects, investigating the genetic basis of diabetes, cardiac disorders, neuromuscular disease and neuropsychiatric disorders. She also sits on the advisory board of the master’s program in bioethics and has co-authored multiple papers with faculty in that program, exploring the ethical and social implications of genetic medicine.

“She is the go-to person for genetic issues at Columbia,” says pediatric cardiologist Teresa Lee, who was a fellow in Chung’s lab and still works there, researching genetic factors in cardiac disease. “She pretty much manages any patient in the hospital with a genetic disorder.”

As a mentor, Chung pushes her students as hard as she pushes herself, Lee says. A few years ago, her graduate students and postdocs hosted a dinner to celebrate Chung winning the Presidential Teaching Award. Each presented Chung with a book for her two sons that reflects lessons he or she had learned from Chung. Lee’s choice was The Little Engine That Could — “because she believed in me sometimes more than I believed in myself,” Lee says.

Family matters:

Chung builds equally strong relationships with her patients and their families. In fact, Cain, the father of one of her patients, is writing a nonfiction book about genetic medicine with Chung as the protagonist.

“She was a great advocate for us,” says Cain, whose son Owen, now 8 years old, was born with spinal muscular atrophy, a neuromuscular disease that is the most common genetic cause of death in infants.

The family endured months of agony and uncertainty until Chung diagnosed the disease just as Owen celebrated his first birthday. Chung’s support and advice meant a great deal to the family as they navigated the complex details of his treatment, Cain says. “It really empowered us to make the right decisions for our son.”

Genetic medicine can pose difficult questions for both clinicians and parents. For example, deletions and duplications in the 16p11.2 region almost always produce some symptoms of autism, but only about 30 percent of individuals with a deletion warrant a diagnosis.

The Simons VIP study aims to understand the full spectrum of the 16p11.2 phenotype, or collection of traits. Until it does, however, it is tricky to advise parents on whether to opt for prenatal tests for the region and other less well-characterized genetic anomalies.

“One way of thinking about this is people can make their own decision,” Chung says. “On the other hand, I can tell you the flip side, the patients who got the intensive arrays and say afterwards, ‘Boy, I really regret making this decision.'”

Still, whenever there is a question about sharing information with families, Chung invariably comes down on the side of patient autonomy, says Christa Lese Martin, director of the genetics laboratory at Emory University in Atlanta, and a co-investigator on the Simons VIP. “She’s always got the family’s needs in mind.”

Leibel adds that Chung also serves as a sounding board for physicians wrestling with such difficult issues at Columbia.

“She’s not talking about theoretical constructs,” he says. “She’s lived them herself, in terms of losing a child for reasons that still remain unknown. I think that’s one of the reasons she’s so sensitive on these points and so effective.”


  • Anonymous

    I have a question for Dr. Chung and the Simons VIP project. Most cases with a 16P11.2 mutation are caused by a germline reproductive error (egg or sperm) and are not inherited events:

    http://ghr.nlm.nih.gov/condition/16p112-deletion-syndrome

    Will the VIP project be studying the complex multifactorial causes of these de novo mutations and if not, why not.

  • Anonymous

    Thanks for your question. The Simons VIP study is recruiting anyone with a 16p11.2 deletion or duplication regardless of whether it is inherited or de novo. Please see here (http://simonsvipconnect.org/) for more information on the scope and goals of the project.

  • Anonymous

    The ~ 500 kilobase microdeletion in 16p11.2 implicated in ASD by Kumar and colleagues (2007) is flanked by segments of duplicated DNA that are >99% identical. Segmental deletions facilitate DNA recombination leading to chromosomal rearrangements. Another region also implicated in ASD is 15q11-q13, where deletion can cause Prader-Willi syndrome or Angelman syndrome, while duplication causes 15q-duplication syndrome (hypotonia, epilepsy, autism, dystonia, developmental delay). Again, this is due to repetitive sequences at a number of places in the 15q11-q13 region (reviewed by Chamberlain SJ & Lalande M, 2010). As these repeat regions are found at many locations in the human genome, de novo mutations can cause many types of genomic disorders, and this is not an ASD-specific phenomenon.

  • Anonymous

    Thank you Dr. Bishop.

    A recently published study of de novo copy number variations has found that location specific copy number variations (1q21.1, 15q11.2, 15q13.3, 16p11.2, 16p13.11, and 22q11.2.) are associated with a broad spectrum of neurodevelopmental and neuropsychiatric conditions including developmental delay, schizophrenia, intellectual disability, autism spectrum, and multiple congenital anomalies.

    http://www.ncbi.nlm.nih.gov/pubmed/21792059

    What is almost never mentioned by SFARI investigators, behavioral geneticists and molecular geneticists whose narrow focus is exclusively on autism is that these do novo CNV’s are pleiotropic and are not diagnosis specific.

    Never mentioned is that in in many single-gene disorders associated with high rates of co-ocurring autism, the genetic and epigenetic cases are almost always de novo, in contrast to being inherited events. The single gene disorders with high rates of co-occuring autism and that are almost always de novo include Rhett Syndrome, Downs Syndrome, Prader-Willis Syndrome, Angelman Syndrome, Klinefelter syndrome and Phelan-McDermid syndrome to name a few.

    The question that is never asked is what are the causes of these de novo mutations in the single gene disorders and in CNV’s. Almost certainly mutagenesis is complex and multifactorial and may involve many interacting influences including , other genetic influences, advanced parental age and certainly environmental influences that all have to be part of explanation.

    The complete disinterest of the SFARi investigators, the behavioral geneticists and the molecular geneticists in researching or even discussing the etiology of mutagenesis is scandalous.

  • Anonymous

    I am interested in autism biobank registries which also have conducted blood analysis (heavy metal, calcium, vitamins) as well as genomic marker analysis. Would you know of some collaborative biobanks that have such data and would share it with other research groups?

    Regards,

    Donna

  • Anonymous

    I have to respectfully disagree with the comments made above by RAJensen. It’s well known by SFARI investigators, and by autism researchers in general, that the recurrent copy number variants cited above are not specific to autism. Indeed, it has been autism researchers themselves (including SFARI investigators) who have shown over the past few years that almost any autism-associated genetic variant you can name also predisposes to other neuropsychiatric disorders. This same group of researchers has also carefully catalogued the relative frequency of de novo vs. inherited mutation, and it was in fact two SFARI investigators (Jonathan Sebat and Michael Wigler) who alerted the field to the importance of de novo mutations in autism. Indeed, the entire effort behind the Simons Simplex Collection is premised on the notion that de novo mutations represent substantial risk factors in a significant fraction of autism cases. Another SFARI investigator, Evan Eichler, has published extensively on the differential impact on risk that de novo and inherited CNVs confer. What causes de novo mutations? For de novo point mutations, the cause is the same cause that underlies all mutations: the cellular machinery for DNA replication is imperfect. Without this imperfection, evolution would not happen. As for recurrent CNVs, several investigators have shown that they are caused by the architecture of the genome itself, with repeat sequences promoting deletions and duplications of DNA either during mitosis or meiosis (see, for example, the work of Eichler and James Lupski). Environmental influences may indeed also be involved, and SFARI investigator Steve Warren has studied the role of cellular stress in generating CNVs in mitotic cells. All told, there has been a huge effort on the part of geneticists to understand the etiology of mutations, going back to the very beginnings of the field.

  • Anonymous

    Dr. Sullivan–to our knowledge, no one is doing the sort of analysis you propose. If you would like to check ongoing projects using SSC biospecimens, you can request access to SFARI Base. Thank you for reading SFARI!

  • Elizabeth Francisco

    My son was recently diagnosed with 1q21.1 duplication what can you tell me about it do they see any improvement with speech. My son is 4 he has mod severe asd,spd,global dev delay

close

Log in to your Spectrum Wiki account

Email Address:

Password:


close

Request your Spectrum Wiki account

Spectrum Wiki is a community of researchers affiliated with an academic or research institutions. To be considered for participation, please fill out this form and a member of our team will respond to your request.

Name:

Email Address:

Title and Lab:

Area of Expertise:

Comments: