By: Ada Chong
March 2022
How do things work?
From your car engine to marine ecosystems, from the frog you dissected in BIO101 to the CFTR protein that underlies the disease cystic fibrosis (CF).
That’s what has interested Nael McCarty, PhD, since he was very young, and led to his passion for physiology. Dr. McCarty is now the Marcus Professor of Cystic Fibrosis in the Emory Department of Pediatrics.
“I’ve always liked biology and trying to understand how things work,” says McCarty. “Once you know the list of parts, you can ask how do they all work together? That speaks to me; I love asking questions about how these functions are accomplished.”
How do things NOT work when they’re broken?
From the kitchen microwave oven that broke last night right before dinner was ready, to the defective CFTR protein in our CF patients, and to the many organ systems that therefore show defects in our CF patients.
And how can we fix things like CFTR when they are broken?
Can we identify new compounds that fix this broken protein? Can we figure out how to overcome the consequences of the loss of CFTR in the lung, in the gut, in the pancreas?
Those are the questions that drive Dr. McCarty now.
Although CF is not in Dr. McCarty’s family, he was inspired to study the CFTR molecule during his postdoctoral research at Caltech in 1992 because of a ten-year-old girl with CF who stopped him and asked, “what are you doing to save my life?” Dr. McCarty said his work at the time, right after the CFTR gene was identified, was years away from treating her, but that question has haunted him ever since. He says CF patients dream of effective therapies and cures and he thinks about the little girl’s question all the time. In 1994, Dr. McCarty started his own lab at the Emory Department of Physiology where he became the Associate Director of Research for the CF Care Program. He tested therapies and diagnoses on patients. Since CF impacts so many organ systems, Dr. McCarty was able to use his skillset in helping answer many important questions. CF impacts the types of cells and processes he likes to think about.
Fast forward to 2010 when the Center for CF and Airways Disease Research (CF-AIR) was created, Dr. McCarty started doing more integrative work that includes other cellular proteins that function alongside of CFTR and that are altered by CFTR’s defects. His own research is impacted by the environment around him, too. The research he can do has expanded because of the connections of people he has brought in. You can imagine it might be hard for someone to understand a complex disease like CF if you only think about it from the perspective of one protein. To enable “Team Science,” CF-AIR has physicians and PhDs working closely together to collaborate and share ideas so they can think about things in different, complementary ways. Our CF team works from bedside-to-bench so the scientists can understand what tools the physicians need in order to best care for our patients.
Because Children’s and Emory jointly manage the second largest CF Clinical program in the country, CF-AIR researchers such as Dr. McCarty try to do work close to the patients. He says 90% of their ~700 patients are involved in research, which is an extraordinarily high degree of engagement. The patients grant permission for Dr. McCarty and his team to use their samples, such as blood and sputum, to do research. Most recently, the CF-AIR team has begun to develop The Georgia CF Data Warehouse to help connect clinical data registries and sample collections to lab data derived from studying those samples, enabling researchers to test new hypotheses about disease progression and how to halt it.
Current research Dr. McCarty is working on includes a focus on CF related diabetes. This disease starts in the pancreas but impacts the lung. The loss of this same protein in the pancreas leads to diabetes in most CF patients. Dr. McCarty says when you have CF related diabetes on top of CF, your lungs’ function declines at an even faster rate. Understanding the mechanism connecting diabetes to worsened lung function is a major goal of his lab’s work.
Dr. McCarty is also working with Mike Koval, PhD, to understand how insulin regulates the function of airway epithelial cells to regulate glucose in the airway. The team showed that not only do CF cells in the lungs allow more glucose to leak into the airway, those CF cells also cannot pull glucose back out. They found that normal lung cells and CF lung cells respond differently to insulin, but they are still trying to figure out why.
“We want to come up with therapies that are impactful, but we need to know where the system breaks,” says Dr. McCarty. “We need to know where the defect is in order to know how to design therapies. In the CF community, we’ve made enormous progress over the last three decades and improved the lives of our patients. Basic science studies have helped show us what’s defective. Now the CF community has learned that we can put these pieces of the puzzle together to come up with new therapies.”
Dr. McCarty is extremely grateful for the collaborative nature of Emory and Children’s that enables the CF research team to do work that is impactful for his patients.
From your car engine to marine ecosystems, from the frog you dissected in BIO101 to the CFTR protein that underlies the disease cystic fibrosis (CF).
That’s what has interested Nael McCarty, PhD, since he was very young, and led to his passion for physiology. Dr. McCarty is now the Marcus Professor of Cystic Fibrosis in the Emory Department of Pediatrics.
“I’ve always liked biology and trying to understand how things work,” says McCarty. “Once you know the list of parts, you can ask how do they all work together? That speaks to me; I love asking questions about how these functions are accomplished.”
How do things NOT work when they’re broken?
From the kitchen microwave oven that broke last night right before dinner was ready, to the defective CFTR protein in our CF patients, and to the many organ systems that therefore show defects in our CF patients.
And how can we fix things like CFTR when they are broken?
Can we identify new compounds that fix this broken protein? Can we figure out how to overcome the consequences of the loss of CFTR in the lung, in the gut, in the pancreas?
Those are the questions that drive Dr. McCarty now.
Although CF is not in Dr. McCarty’s family, he was inspired to study the CFTR molecule during his postdoctoral research at Caltech in 1992 because of a ten-year-old girl with CF who stopped him and asked, “what are you doing to save my life?” Dr. McCarty said his work at the time, right after the CFTR gene was identified, was years away from treating her, but that question has haunted him ever since. He says CF patients dream of effective therapies and cures and he thinks about the little girl’s question all the time. In 1994, Dr. McCarty started his own lab at the Emory Department of Physiology where he became the Associate Director of Research for the CF Care Program. He tested therapies and diagnoses on patients. Since CF impacts so many organ systems, Dr. McCarty was able to use his skillset in helping answer many important questions. CF impacts the types of cells and processes he likes to think about.
Fast forward to 2010 when the Center for CF and Airways Disease Research (CF-AIR) was created, Dr. McCarty started doing more integrative work that includes other cellular proteins that function alongside of CFTR and that are altered by CFTR’s defects. His own research is impacted by the environment around him, too. The research he can do has expanded because of the connections of people he has brought in. You can imagine it might be hard for someone to understand a complex disease like CF if you only think about it from the perspective of one protein. To enable “Team Science,” CF-AIR has physicians and PhDs working closely together to collaborate and share ideas so they can think about things in different, complementary ways. Our CF team works from bedside-to-bench so the scientists can understand what tools the physicians need in order to best care for our patients.
Because Children’s and Emory jointly manage the second largest CF Clinical program in the country, CF-AIR researchers such as Dr. McCarty try to do work close to the patients. He says 90% of their ~700 patients are involved in research, which is an extraordinarily high degree of engagement. The patients grant permission for Dr. McCarty and his team to use their samples, such as blood and sputum, to do research. Most recently, the CF-AIR team has begun to develop The Georgia CF Data Warehouse to help connect clinical data registries and sample collections to lab data derived from studying those samples, enabling researchers to test new hypotheses about disease progression and how to halt it.
Current research Dr. McCarty is working on includes a focus on CF related diabetes. This disease starts in the pancreas but impacts the lung. The loss of this same protein in the pancreas leads to diabetes in most CF patients. Dr. McCarty says when you have CF related diabetes on top of CF, your lungs’ function declines at an even faster rate. Understanding the mechanism connecting diabetes to worsened lung function is a major goal of his lab’s work.
Dr. McCarty is also working with Mike Koval, PhD, to understand how insulin regulates the function of airway epithelial cells to regulate glucose in the airway. The team showed that not only do CF cells in the lungs allow more glucose to leak into the airway, those CF cells also cannot pull glucose back out. They found that normal lung cells and CF lung cells respond differently to insulin, but they are still trying to figure out why.
“We want to come up with therapies that are impactful, but we need to know where the system breaks,” says Dr. McCarty. “We need to know where the defect is in order to know how to design therapies. In the CF community, we’ve made enormous progress over the last three decades and improved the lives of our patients. Basic science studies have helped show us what’s defective. Now the CF community has learned that we can put these pieces of the puzzle together to come up with new therapies.”
Dr. McCarty is extremely grateful for the collaborative nature of Emory and Children’s that enables the CF research team to do work that is impactful for his patients.