Faculty Q&A with Wendy Chung: Exploring Genetic Approaches to Medicine

Columbia News
November 23, 2015

Wendy Chung started medical school the same year that the daunting project of sequencing the human genome began. She realized that when she finished her training, the work would be done and someone would need to know what to do with all that information—so she focused her energy on acquiring the skills to find genes and treat genetic diseases.

“This is one time in medical history when we have a unique opportunity because we have actually sequenced the human genome. We know what most of those genes do. We have the computer power to analyze the data and the electronic medical records, gather clinical data and disseminate the knowledge of how to use the data relatively quickly,” said Chung.

Chung is part of Columbia’s Precision Medicine Initiative, which aims to improve patient care based upon genetic and other information specific to each individual patient. Launched in 2014 when President Lee C. Bollinger appointed pioneering molecular biologist Tom Maniatis as its director, the initiative is taking shape not only across the University’s clinical disciplines and the basic sciences, but also in the fields of data science, engineering, law, public policy and ethics.

“Wendy has been a real pioneer in clinical genetics at Columbia—in her work with childhood diseases and serving as a strong advocate for genetics more broadly through her work at the NIH—Wendy is often known to emphatically exclaim: ‘Its all about genetics!’ ” said Maniatis. “Genetic medicine is about making sure that patients come first and that our treatments are in line with their goals,” said Chung, who specializes in pediatric medicine. Chung realized that she also wanted to help address fundamental ethical questions of genetic medicine. These include how to ensure equal access to care and limit the possibility of genetic discrimination in employment or insurance based on a predisposition for certain diseases as well as considering the societal implications of altering genes. Or, as she put it, “Just because we can do something, doesn’t mean we should.”

“It’s not just the doctors deciding,” she said. “It’s really about the community thinking about this together and coming up with solutions.”

“As exciting as these opportunities in precision medicine are, it’s important to emphasize that we are just at the beginning of the process of progressing from the discovery of disease-causing mutations to an understanding of how these mutations actually cause disease,” said Maniatis. “The latter, which is a prerequisite for developing effective therapies and prevention strategies, will require major advances in the basic sciences that underlie human physiology. That’s why the goal of the Columbia Precision Medicine Initiative is to bring our collective intellectual and clinical expertise to bear on these very significant and fundamental challenges.”

Q. What is your research focus?

A. My research is relatively broad. I’m a human geneticist, and what I do in partnership with my patients is answer their question, “Why did I develop this condition?” When we can’t get answers with routine clinical care, we use our research tools to discover new genes for human diseases. Once we identify those genes, we have to describe the clinical features and understand how the gene causes the new condition that we’ve now described, and how we can support the patients and ultimately treat them.

Q. How do you define precision medicine in your practice?

A. Precision medicine in simple terms is the right treatment for the right patient at the right time in the right way. Not all cancer is the same, for instance, so we fine-tune our treatment to try to limit the toxicity and side effects of medications and make sure patients have the best chance of benefiting from what we prescribe. And it’s not just about treating a patient once they’re sick, but also about trying to prevent problems from happening in the first place.

Q. Before the era of gene discovery, was there room for this sort of personal approach in clinical settings?

A. Historically we’ve relied on family history, what you might be at risk for based on the diseases in your family. We can do better than that now by using genetic information and looking at what’s going on in your body in real time. Are you starting to develop the early stages of disease? Can we detect those early stages before you develop symptoms? If so, sometimes we can halt things right in their tracks. Or reverse things and put the patient back into a better state of health.

Q. What is the greatest challenge to using genetics for preventive care?

A. The next big frontier is going to be to take a healthy person and try to predict whether or not they’re going to have disease, and if so, what disease, when, and how severe. Also, we have to make genetic testing more equitable. We don’t have the genomic workforce right now so everyone can get a genetic health checkup. We need to build the infrastructure to do this not just in 1,000 patients a year at Columbia, but 100,000 patients a year. The cruel reality is, even when I can make a diagnosis, I can only translate that immediately into an effective treatment probably 10 percent of the time. We need to be able to take our understanding of disease mechanisms and turn it into improved therapies. Also, we have not done a very good job as researchers of bringing everyone into our studies, in particular Latinos, African Americans, Asians and many other people from different corners of the globe. We do not understand enough about what’s normal and what’s different about those individuals in terms of disease predisposition. And that’s just not fair.

Q. You've recently discovered a genetic connection between congenital heart disease and neurodevelopmental disabilities in children. Can you tell us what you found?

A. About 10 percent of babies with congenital heart disease—which affects the development, structure, and function of the heart—are later diagnosed with neurodevelopmental disorders, such as learning disabilities and attention-deficit hyperactivity disorder. One possible explanation is that children with congenital heart disease may be deprived of sufficient blood and oxygen flow during critical moments in brain development. Innovations in cardiac surgery and cardiac care mean that most children with complex heart problems now survive the newborn period. Using the sophisticated tools of genomic sequencing, we have the ability to look deeply within the genome and determine if these conditions are genetically linked. Identification of an underlying genetic cause would allow us to predict the risk of neurodevelopmental disorders in individuals with congenital heart disease, allowing us to intervene while the brain is still growing and developing. I think we will begin to see genomic sequencing move out of the realm of research and into the clinic as a diagnostic tool with the power to predict the risk of many kinds of conditions. This is truly precision medicine at its best.

Q. You work in the Department of Pediatrics. Is there a different approach to dealing with children than in dealing with adults?

A. About half my patients are children and about half are adults. I don’t really care about how old my patients are, but it is true that there’s a greater burden of very serious genetic conditions in children because unfortunately many of them don’t survive to adulthood. So we have historically seen more genetic medicine in pediatrics. Though the concepts are the same whether you are 15 or 50, there are some things that we’re very conscious of with children. They are still developing, their bodies and minds are changing, so we think about that in terms of how diseases evolve and how our treatments affect the children as they develop.

Q. One focus of your research is autism. What have you found?

A. Autism is really an umbrella diagnosis; there’s not one single type of autism nor is there one single cause. It’s a constellation of behaviors that can travel together. I see children with attention deficit disorder or anxiety who may have some overlapping features of children with autism. One gene may cause autism in one individual, but in another person express itself in other intellectual disabilities and in a third person, be compatible with normal behavior depending on the rest of the genome, the gender, and other early developmental exposures.

Q. Your team recently discovered a gene involved in pulmonary hypertension. Is there now a treatment for the disease?

A. Pulmonary hypertension, thankfully, is relatively rare. It’s a condition in which the pulmonary arteries clamp down and blood pressure in the lungs goes up. In studying the disease, my group discovered that one particular potassium channel is very important for regulating blood pressure in the lungs. There are pills you can take to change how channels open and close that we use to prevent seizures and arrhythmias. The hope is that we might be able to use some of that same pharmacology to treat pulmonary hypertension. None of us would have thought of repurposing those medications had it not been for genetics.

Q. Precision medicine looks at mutations of the human genome. What is the treatment approach for mutations such as cancer that develop during a person’s lifetime?

A. At birth you’re dealt a certain set of genes from your parents. But your genes can change over your lifetime. The disease that’s most commonly associated with this is cancer, which is the accumulation of many mutations in cells to the point that those cells start going wild. They grow rapidly and invade places they shouldn’t. The precision medicine approach for oncology is to figure out cancer’s Achilles heel. Where is it weak? Cancer cells are actually more vulnerable than normal cells. So we can use targeted therapy based upon the mutations in the cancer and including ways to activate the immune system to destroy the cancer without producing collateral damage in the rest of the body.

Q. Can you tell us about the work you’ve done on diabetes?

A. For the last 10 years we’ve been working with endocrinologists at the Naomi Berrie Diabetes Center to identify patients who don’t exactly fit the profile of type 1 or type 2 diabetes to try to understand their genes better. We’ve been able to identify many patients who were being over-treated and put them on oral medications or in some cases, just prescribe changes in diet and exercise. They no longer need to take insulin injections or check their sugar all the time. You cannot imagine what great a relief that is for a family, especially for a family with a young child. On the other hand, in some cases we’ve realized that a person’s type of diabetes is much more serious and involves other medical problems beyond diabetes and requires very aggressive treatment that we might not otherwise have thought to use. All of these cases underscore the idea that all diabetes is not the same. Finding the genes can help us tell you what your road map is so your treatment is not just trial and error.

Q. What is distinctive about Columbia’s interdisciplinary approach to this kind of clinical research?

A. The greatest asset we have here at Columbia is the University community—the faculty, support staff, graduate students, post-docs. It’s an amazing wealth of human intellect and talent. Also, we’re not just a medical school; we also have engineers, mathematicians, physicists and statisticians who know how to take huge amounts of data and see patterns. And we have scholars in the humanities—sociologists, philosophers and historians, for instance—who think about the human dimension of what we do and ensure that at the heart of all our endeavors, we’re doing something that benefits everyone. Finally, we are living at a time when we can and do use social media to speed up access to information and help patients with rare disorders connect to others with the same disease, not just in the United States but anywhere in the world, making this a global effort.