Dr. Mary Estes serves as Distinguished Service Professor in the Departments of Molecular Virology and °®¶¹´«Ã½ and of Medicine (Infectious Diseases and Gastroenterology and Hepatology Divisions) at Baylor College of Medicine in Houston. ASM sat down with Dr. Estes to reflect on her career and experiences in the fight against COVID-19.
Dr. Mary K. Estes
Dr. Estes, could you give us a synopsis of your background and research?
I have enjoyed a rich, varied and stimulating career. I always loved biology and my family, and I thought I would go to medical school. I volunteered in several hospitals where I was always asking questions about what caused untreatable diseases and how such information might lead to new ways to prevent or treat such diseases.
As an undergraduate, I trained in biology and got involved in my first research project. I learned how important microbes are in many food processes and found many different microbes exist that cause a wide spectrum of diseases. I also learned one could get a Ph.D. degree to ask fundamental questions about how to prevent and treat many infectious diseases. I was delighted to have the opportunity to study microbiology and immunology at the University of North Carolina in Chapel Hill. I planned to study immunology, but my first exposure to virology changed my direction.
Virology became my passion, and I still cannot learn enough about these fascinating, invisible microbes that affect cells and hosts in so many ways. I minored in biochemistry and became a molecular virologist with an interest in understanding how viruses cause disease (pathogenesis) and how infected hosts respond to infection (immunity). I first studied 40, a virus that can cause cancer, and I loved learning new techniques. I moved with my husband, a marine geologist, and our young son to Texas, where I pursued postdoctoral training in virology and epidemiology at Baylor College of Medicine in Houston.
After joining the faculty at Baylor, I began to study viruses that cause life-threatening gastrointestinal disease in humans and animals (and . These viruses have become remarkable tools to understand gastrointestinal biology and mucosal immunology. I now direct a multidisciplinary research program to understand gastrointestinal (GI) disease including host-microbe interactions and develop methods to prevent and treat global disease. My research includes molecular studies that have resulted in significant basic science discoveries related to GI virus replication and viral pathogenesis as well as translation of these discoveries into candidate vaccines. During my research career, I have found that it is good to be flexible—it is possible to change plans—and I enjoy new endeavors.
What has presented the biggest challenge in your field or work?
Challenges varied based on my career stage. Most consistently though, are times when it has been difficult to obtain funding for our research.
Although it seemed odd to me, many people failed to appreciate the importance of gastroenteritis as a global disease and to recognize that research on new gastroenteritis viruses was important. In recent times, with vaccines available for rotaviruses, people question whether there is value in the continued study of these viruses.
While rotavirus vaccines work well in developed countries, they are not as effective in low-income countries where they are needed most. We need to understand why as well as find ways to improve responses to these vaccines in high disease burden settings. Other studies of human rotaviruses continue to discover new mechanisms of pathogenesis and virus-host interactions, including insights on host metabolic changes that occur following infection. It may seem counterintuitive to some, but these viruses continue to be great models to understand fundamental GI biology and disease.
Similarly, it took many years to recognize noroviruses as important human pathogens. These human-specific viruses have been challenging to study because they did not replicate for almost 50 years in any cultured cells in the laboratory. Fortunately, we now have stem cell-derived human intestinal organoid cultures to grow human noroviruses, and these cultures are transforming our ability to study previously non-cultivatable microbes and allowing new studies of therapies. This is one example of how advances in other fields (stem cell biology and developmental biology) have led to new technology that allowed us to overcome a longstanding barrier in a different scientific field. New technology drives innovation and new discoveries.
What do you consider the most rewarding part of your career?
Making unexpected discoveries about the viruses I study resulted in great surprises, important knowledge and led to 2 candidate vaccines. This has been very rewarding. Learning that rotaviruses make a viral enterotoxin changed our thinking about how these viruses cause disease. Being able to grow the host-restricted human noroviruses in non-transformed stem-cell derived human intestinal organoids is now allowing us to test inactivating agents, antivirals and to understand how immunity protects against these infections.
Because gastroenteritis is a global disease, I have visited many countries in Asia, South America, Australia, and Europe where I have been able to collaborate with wonderful investigators. I enjoy meeting new people, and our discoveries have been accomplished by a great team of investigators with diverse expertise including basic scientists, clinicians, staff and trainees. I have dedicated part of my career to teaching and mentoring trainees. Sharing my expertise with others is always fun, and it has been a pleasure to learn new perspectives and to watch my colleagues and trainees build and move into a variety of successful careers. I am grateful to my mentors, colleagues and trainees who have shared in the joy of answering questions to help us tackle the fascinating GI viral pathogens. I am grateful to ASM for honoring me with the Lifetime Achievement Award, and I am delighted that it recognizes my rewarding career as a virologist and our team’s effort and success.
How has the COVID-19 pandemic impacted your work? How do you cope with those changes?
Since March 20, our lab has been mostly closed, which has been challenging. We have coped with not being able to conduct experiments by analyzing previous data, reading and writing papers and grants while working from home. I have meetings on Zoom to remain connected with my group and colleagues. I think every virologist and scientist I know has asked themselves how their special expertise can be helpful to understand this pandemic virus and its devastating effects on our local, national and global communities. For example, I initially led a COVID biological responses subgroup in Baylor on cell biology, and it was fascinating to see scientists from diverse fields, from neuroscience to virology, come together to discuss ideas and develop innovative ways to understand this incredible disease and help the local and global scientific community.
This pandemic reminds us of the important role of the ASM community and Academy Fellows as scientific leaders to help address societal needs. What advice would you give to your trainees as they pursue a career in science?
Read broadly, and find an area of science that is your passion. The training microbiologists receive enables them to think critically and solve many challenges. It is also important to learn to work with others in teams to learn and benefit from different expertise and experiences. This diversity of experiences and thought processes enriches final solutions. One does not need to be a virologist to contribute to helping overcome this pandemic. Each of us likely has many talents that can be used to tackle this historic event.
Looking forward, what makes you most excited about the future of the field of microbiology?
°®¶¹´«Ã½ affects all living organisms and is important to almost all aspects of our lives. There are so many areas of both basic and applied microbiology to consider studying. Today, microbiologists have a vast armamentarium of tools available to solve many problems that impact the global population. I am confident these challenges can be solved if we remain flexible and innovative in how we apply our expertise. Again, teamwork is essential to analyze and solve the interdisciplinary problems facing us today and in the future. This is illustrated well in how scientists from many fields have come together across the globe to tackle the global pandemic we are now facing.
