TMC PULSE

t m c » p u l s e | j u ly 2 0 1 5 11 Q | Can you tell us a bit about your formative years? A | I was born in Beirut, Lebanon, and was fortunate to have a family who valued scholarship. My parents always encouraged me to study and my biblio- phile dad would spend hours reading in his huge library. His library was filled with books from floor to ceiling, a room I enjoyed spending time in as well. I attended school in Beirut. I fell in love with English literature in high school and decided to declare it my major once I enrolled in a university. My mom disagreed. She felt that literature was not the right path for me, which led to quite a few arguments. She would say, 'I can't believe that you are so good in biology but you are going to study English literature just because you like reading and writing. You can do that as a hobby and focus on medicine professionally. For a woman it will be much better to have a career in medicine than to be a writer.' I even- tually began to understand her point, and after much discussion, ultimately entered the pre-med program at the American University of Beirut. Q | What led you to Houston? A | I completed my pre-med degree at the American University of Beirut and then began medical school there. I was very happy living in Beirut. The city was at its peak, a dream place to be. When the civil war began, however, the quality of life in Beirut quickly deteriorated. Towards the end of my first year of medical school, Beirut was becom- ing quite dangerous and my parents suggested that I spend the summer with my sister who was living in Austin, Texas, at the time. I arrived in Texas thinking that my stay would only last through the summer. Unfortunately, the war continued to escalate during those months and I decided to transfer to a medical school in the United States. I ultimately enrolled in Meharry Medical College in Nashville, Tennessee. While in Nashville, I traveled to Houston for electives at Baylor College of Medicine. During one of my trips, I met Dr. Ralph Feigin, chairman of pedi- atrics at Baylor and physician-in-chief at Texas Children's Hospital. He encouraged me to consider the pro- gram here and asked, 'What can I do to get you to come to Baylor?' He didn't have to do much as I quickly knew Baylor was the right choice for my residency. When I arrived at Baylor, I studied pediatrics and neurology and just loved it, truly enjoying my residency years. For someone who's been transplanted as an immigrant, not knowing anyone in Houston, the program became my family and Dr. Feigin became like a second father to me. I decided to stay for additional training. I was trained as a physician, but patient encounters during my pediatric neurology residency inspired me to get research training and led me into science. It was 1985. At the time, the best you could do for a patient with a neurological disease was to meet with the family members, tell them the likely diagnosis, let them know it was probably a genetic disorder that could happen again, and let them know there was unfortunately nothing to be done. It was devastating, to say the least. That's what compelled me to go into the lab. I wanted to learn what I could about biology and genetics, and how to find disease genes so that we could diag- nose more accurately and help families by eventually understanding how to treat these devastating disorders. Q | Are there any moments from your career that stand out as being your proudest achievements? A | Making a discovery in an area that I'd been working on for years always stands out—knowing how important it is for us to understand how to solve a neurological problem or better treat a disease. Those moments stand out the most. HUDA Y. ZOGHBI, M.D., PROFESSOR IN THE DEPARTMENT OF MOLECULAR AND HUMAN GENETICS AT BAYLOR COLLEGE OF MEDICINE AND DIRECTOR OF THE JAN AND DAN DUNCAN NEUROLOGICAL RESEARCH INSTITUTE AT TEXAS CHILDREN'S HOSPITAL, HAS HAD AN EXCEPTIONAL CAREER. FROM HER EARLY DAYS AS A MEDICAL RESIDENT IN PEDIATRIC NEUROLOGY TO HER RESEARCH ROLE IN THE DISCOVERY OF THE GENE FOR RETT SYNDROME, ZOGHBI HAS ALWAYS HAD A DESIRE TO GIVE FAMILIES THE ANSWERS THEY NEED WHEN FACED WITH A DEVASTATING DIAGNOSIS. It was a very exciting time when we found the Rett syndrome gene, because it was a result of a 16-year search. When you wait for something for 16 years and it finally comes, it's an unbelievable feeling. TMC SPOTLIGHT I will never forget the day my collaborator, Harry Orr, and I simulta- neously sent each other faxes. We were both exchanging the discovery of the spinocerebellar ataxia 1 mutation in our respective labs. We had been collaborat- ing and both discovered the mutation on the very same day. I will never forget that. It's our special anniversary— April 8, 1993, and we always congratu- late each other on that day. On another occasion, I was return- ing from a family trip to Lebanon with my children and as I was putting the key in the door, I heard the phone ring- ing. I picked it up and my postdoctoral fellow, Ruthie Amir, said, 'We found a change in a gene in Rett syndrome patients. Can I show you the data?' And I said, 'Absolutely. Yes!' I had just trav- eled for 24 hours, yet I still wanted her to come to the house immediately with all her data. That moment, the excite- ment of seeing the changes for the very first time, plays over and over again in my head. A few days later we wrote the paper, and two days after that, the paper was accepted. It was a very exciting time when we found the Rett syndrome gene, because it was a result of a 16-year search. When you wait for something for 16 years and it finally comes, it's an unbelievable feeling. Those two discoveries are the moments that truly stand out. There are many others, of course. When students I've mentored and grown to love grad- uate, or when my first fellow received a faculty position, I'm holding back a tear. These are all very special and the moments that I am the most proud of. And then, of course, to be recognized for what I love to do is so meaningful and such a privilege. Q | Speaking of your discoveries, can you tell us a little bit about what those mean? And what has been the impact of those discoveries? A | There have been several different discoveries and each has had a different impact. Our first discovery was a gene that causes neurodegeneration. It's an inherited disease called spinocere- bellar ataxia type 1 (SCA1) that affects balance. Patients experience gradual neurodegeneration and ultimately die from the disease. It's a rare disease, but is a typical adult neurodegen- erative disease, which means that it shares features with diseases such as Alzheimer's and Parkinson's. A patient can be healthy for decades and then the symptoms appear. Because we found the gene for this terrible disor- der, we can now provide families with the opportunity for early diagnosis. If the family is affected, they can then choose what lifestyle changes they may want to make. Some may choose not to have children, or to adopt children, so that they eliminate the occurrence of the disease in their family. So many patients and their families are grateful for this knowledge. Once we finally identify a gene, we are able to create an animal model that closely mimics the human disease. This allows us to better understand how, when a particular gene mutates, it wreaks havoc in the neurons. We found out how the mutated gene affects brain cells and what we might be able to do about it.

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