From Bench to Bedside: Physician Researcher Amber Luong, MD, PhD Blends Basic Science with Clinical CareAs a child growing up in a strong, extended family of physicians, Amber U. Luong, MD, PhD, developed an avid interest in medicine and in caring for patients with disease. But it wasn’t until the early 1990s, when she was an undergraduate biology major at Trinity University, a liberal arts school in San Antonio, Texas, that her interest in research really blossomed.
“In college I started doing basic science research by providing paternity testing services for a colony of chimpanzees,” Dr. Luong says. “Just 40 years earlier, Watson and Crick had presented the structure of the DNA double helix, the molecule that carries genetic information from one generation to the next, and there I was in the lab – a college student – actually seeing DNA and extracting it from cells. That was a big wow for me. The concept was fascinating. Polymerase chain reaction or PCR that could amplify copies of a piece of DNA across several orders of magnitude had been developed less than a decade earlier. I was very young, and I was working in the lab actually utilizing PCR to generate copies of DNA sequences and studying them.”
It was a heady experience for a 19 year old, and Dr. Luong was hooked. She applied for and was accepted to the Summer Undergraduate Research Program at The University of Texas Southwestern Medical Center in Dallas, where she had the opportunity to work under two Nobel laureates, Michael S. Brown, MD and Joseph L. Goldstein, MD, who run the Brown/Goldstein Lab in the department of Molecular Genetics at the medical center. The two internal medicine specialists have worked together for the last 30 years on the genetics and regulation of cholesterol metabolism. Their discovery of the LDL receptor as the major molecule regulating cholesterol metabolism and its genetic disruption in familial hypercholesterolemia has been recognized by numerous awards, including the Nobel Prize in Physiology or Medicine in 1985 and the U.S. National Medal of Science in 1988.
“They served as great role models,” Dr. Luong says. “I thought, ‘Here are two physicians who have evolved from caring for individual patients to conducting research where the new knowledge they acquire will help hundreds of patients.’ For the first time I understood that you can design a medical career that combines clinical medicine and basic science research to create a unique perspective as a clinician and a scientist. As a physician-scientist you can learn about the disease process as it manifests in patients, each of whom are very different, and use that knowledge and experience to frame research questions and interpret results in the lab. And the opposite is also true. I often gain information as a scientist that makes me think about its applicability to the treatment or the understanding of human diseases. By bringing together these two worlds, translational medicine is born.”
With the support of Drs. Brown and Goldstein, Dr. Luong was accepted to the National Institutes of Health-sponsored Medical Scientist Training Program at UT Southwestern Medical Center, where she earned her MD/PhD. During the eight-year program, the two Nobel laureates served as mentors for her PhD work. Following an internship in general surgery and a residency in otolaryngology-head and neck surgery at the same institution, she completed a fellowship in rhinology and endoscopic skull base surgery at the Cleveland Clinic Foundation, where she worked with Martin J. Citardi, MD, who is now professor and chair of the Department of Otorhinolaryngology—Head and Neck Surgery at the UTHealth Medical School and chief of otorhinolaryngology-head and neck surgery at Memorial Hermann-Texas Medical Center. In 2008, Dr. Citardi recruited Dr. Luong to UTHealth, where she is an assistant professor with a joint appointment in immunology at The University of Texas M. D. Anderson Cancer Center.
Since her arrival at UTHealth and Memorial Hermann-TMC, she has focused her attention and energy on caring for patients and building a translational otorhinolaryngology research program from the ground up. Her primary clinical and research interest centers on understanding the pathophysiology of chronic rhinosinusitis (CRS) as a model for studying immune dysregulation of the paranasal sinuses.
“In our practice we have three fellowship-trained rhinologists, myself included, who treat patients with chronic rhinosinusitis,” Dr. Luong says. “My particular interest in doing research on CRS stems from the fact that we don’t fully understand the disease process of a condition that is diagnosed in more than 3 million Americans each year and accounts for about $6 billion annually in treatment costs. We have knowledge of some of the potential triggers for CRS – viruses, bacteria and fungal exposure – but we aren’t certain which of the triggers affects individual patients. Our research goal is to develop directed curative treatment options for CRS through a better understanding of the triggers and molecular mechanisms that are important in the disease process. Learning more about CRS will give us a better idea of how to design treatments for the cause of the disorder rather than just the symptoms, which is the focus of current treatment.”
Toward that goal, Dr. Luong and her research team are characterizing the bacterial and fungal organisms found within diseased sinuses and the immune response triggered by these organisms, as well as identifying key immune cells and molecules such as thymic stromal lymphopoeitin (TSLP) and IL-33, which are known to trigger the type of inflammatory response seen in CRS.
“Clinically, CRS patients may have similar symptoms – thick or discolored postnasal drainage and facial pain around the cheeks, in the forehead or between the eyes. But when we examine and treat them, it’s clear that there are clinical subsets with different immune responses,” she says. “We see patients with chronic rhinosinusitis who have nasal polyps and those who don’t, and patients who have asthma or allergies and those who don’t.”
A patient Dr. Luong recently took to surgery had a severe form of CRS known as allergic fungal rhinosinusitis (AFRS). Like many of the patients she and her colleagues treat, he had extensive nasal polyposis that made it almost impossible for him to breathe. He also had chronic drainage that required him to interrupt his work to blow his nose every five or six minutes, and the thick mucus would drain into his throat, causing swallowing problems.
“He had very thick mucin packing his sinuses, which, when examined under the microscope, revealed the presence of fungus,” she says. “So in his particular case, we believe that fungus has played a role in the disease process. Unfortunately, we don’t yet have the tools to classify the categories properly, and as a result, we don’t have well-defined treatment options at this point.”
For her AFRS patient, Dr. Luong initially prescribed a course of oral prednisone and antibiotics, which had little effect on his sinus disease, a response far from atypical. “In his situation, surgery was an imperative first line of treatment, followed by close postoperative care, which is critically important,” she says. “After surgery, he had immediate improvements in his quality of life. He no longer has to blow his nose as often and is sleeping better because he can breathe. He can now manage his own treatment at home with irrigations, and if he has a flare-up, we obtain cultures and prescribe appropriate medications that go directly into his irrigation, treating the acute exacerbation. Other patients with less severe sinus disease have responded well to medical therapy. So there’s an art to identifying patients who will respond to medical management and those who may require surgery or even extensive surgery.”
Dr. Luong and her colleagues at the Texas Sinus Institute, who include Dr. Citardi and Samer Fakhri, M., FACS, FRCS(C), an associate professor and residency program director in the department of Otorhinolaryngology-Head and Neck Surgery, know that while surgery in appropriate patients may be a good initial step in treatment, patients are at risk of relapse as long as the cause of the disease is not well understood. Through her research, she’s seeking to discover the best course for continued CRS patient management once surgery allows access to the diseased sinus mucosa.
“Is there a more direct and effective agent than the anti-inflammatory medications we’re currently using?” she asks. “In a subset of patients, we find the presence of fungus. So the research question becomes, ‘Does the inflammation incited by CRS allow fungus and bacteria to live in the sinus or do the bacteria and fungus cause the disease?’ It’s a chicken-and-egg problem and as rhinologists, we won’t be able to solve it until we can characterize the immune response within the diseased sinus mucosa.”
As part of her research, she and her rhinology colleagues are collecting tissue and blood samples during surgery from patients who have consented, as well as fluids from their sinuses and from their lungs, since many of them also have asthma. They’re also collecting tissue from healthy controls for comparison.
Using the samples, Dr. Luong and her research team are characterizing the inflammatory response in patients and the type of growth – bacterial or fungal – present within the diseased sinuses. They’ve generated an enormous patient database for which she serves as the point person, taking what her colleagues see from a clinical perspective to the lab, synthesizing it and bringing it back to the exam room and bedside.
“I’m fortunate to be a surgeon working with other rhinologists, which means that our research is not constrained by the limitations of access to human tissue. Ultimately, we would like to take some of the understanding we gain from human diseased tissue to the mouse model, where we can begin to tackle the chick-and-the-egg dilemma.”
In addition to basic science studies on the pathophysiology of CRS, another focus of Dr. Luong’s is the search for effective treatment for chronic rhinosinusitis, including the investigation and assessment of topical treatment options with various steroid formulations and the novel use of manuka honey. Her team is also studying the use of optical rhinometry to better define nasal physiology and assess nasal patency in allergic and non-allergic rhinitis.
In addition to leading the basic science research program for the Texas Sinus Institute, Dr. Luong has launched a nasal physiology laboratory, a new clinical service for patients with persistent symptoms of nasal congestion and obstruction. Through the lab, she is able to provide objective data for complaints of nasal congestion and can assess lung function in patients with asthma, which is found in a high percentage of CRS patients. The two conditions are linked: exacerbation of CRS can worsen asthma symptoms and improved management of CRS can improve asthma symptoms.
“We’re using new technology in the lab to better assess our patients, which will lead to the establishment of new treatment standards,” she says. “Breakthroughs in the lab mean that ultimately, we’ll be able to help many more patients. It’s very rewarding to successfully treat one patient, but it’s also great to be able to help many patients through research. Research gives you a better understanding of the disease and allows you to leave a legacy. You have the opportunity to touch the lives of hundreds of thousands of patients around the world. Our entire research program is a grand project. We’re looking for a cure for chronic sinus disease. Our long-term goal is to put ourselves out of business.”