Doctoral alumnus, recipient of prestigious NIH research fellowship discusses crucial mentoring he received, advises graduate students to ‘seize the unique opportunity’
Robert M. Brosh Jr., who received his doctorate in biology from the University of North Carolina at Chapel Hill, began his own laboratory at the National Institute on Aging (NIA) in 2000. In summer 2018, he was named a recipient of a prestigious collaborative research fellowship through the NIA and National Institute of Environmental Health Sciences (NIEHS). This work focuses on proteins (helicases) that are connected to a multitude of human disorders and, Brosh says, represents “a new and exciting direction for my lab that grew out of my training in graduate school at Carolina.”
Brosh says that Steve Matson, dean of The Graduate School and biology professor, was instrumental in his success as a doctoral student. In addition, Nobel Laureates Aziz Sancar, of UNC-Chapel Hill, and Paul Modrich, of Duke University, served on his Ph.D. thesis committee.
Brosh shares his own perspective – and advice to Carolina graduate students – with Carolina Graduate School Magazine.
Are there any specific examples of support – professional development, mentoring, other – that helped you advance your academic and professional goals?
I greatly value my coursework as well as my bench science laboratory experiences during my graduate school days at UNC-Chapel Hill. During my graduate training at Carolina, I studied bacterial DNA helicases under the supervision of Professor Steve Matson in the biology department. Bacteria, with their rapid doubling times, proved to be an ideal biological system to readily test my hypotheses in an efficient manner. Looking back, I recognize that my training in Dr. Matson’s lab afforded me the opportunity to develop expertise in both genetics and biochemistry. With sound advice and guidance from my Ph.D. thesis adviser, I was well positioned to explore the world of DNA repair by concentrating my efforts on DNA helicases, a unique class of enzymes that sense and repair damaged sites in the genome.
As I was entering my final years of graduate school at Carolina preparing for my Ph.D. thesis defense, the field of DNA helicases began to blossom in the mid-1990s when researchers discovered that mutations in DNA helicase genes are linked to DNA repair diseases that displayed features of premature aging and elevated cancer. This was an incredibly exciting time for our lab as we realized that our research in basic science had real implications for human health. My training at Carolina provided the perfect springboard to do postdoctoral training and begin a career at the National Institutes of Health, where I lead my own lab in biomedical research on DNA repair diseases as a principal investigator. It is now becoming apparent that helicases play important roles in other facets of biology including cellular metabolism and inflammation. Quite recently, Dr. Fred Miller (NIEHS) and I were awarded a joint grant to study mutations in helicase genes underlying autoimmune disorders. This represents a new and exciting direction for my lab that grew out of my training in graduate school at Carolina.
What should people know about your work?
I am a principal investigator at the National Institute on Aging (NIA), one of the 27 institutes and centers of the National Institutes of Health whose mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability. My lab at NIA studies DNA repair and aging. We are particularly interested in understanding the molecular and cellular basis for hereditary diseases characterized by accelerated aging and genomic instability. Genetic mutations in a class of molecular motor proteins known as DNA helicases are linked to a growing number of human disorders, indicating that these enzymes have vital specialized roles during replication, DNA repair, recombination and transcription. My research team believes that defining the biochemical and cellular functions of DNA helicases will help us understand molecular defects associated with chromosomal variability, aging and cancer.
In reflecting back on your years as a graduate student at Carolina, what experiences did you value the most here at UNC-Chapel Hill?
In addition to the lab work, there were special opportunities during graduate school at Carolina to think outside the box and network with other scientists in my field. One example is the annual retreat for DNA repair scientists and graduate students from UNC, Duke and NIEHS. Instead of printed posters, graduate students present their research topics by drawing on easel artist notepads to explain their hypotheses and experimental approaches. The “poster session” was held outside on the lawn and kept informal so that students and faculty would actively discuss the merits and potential hurdles of the research projects. I also attended outstanding scientific conferences and seminars by experts in the field of DNA repair. It was at one such seminar that I first heard Carolina’s own Nobel Laureate Dr. Aziz Sancar describe his molecular matchmaker model of nucleotide excision repair, a very exciting topic that paved the way for a whole field of study in protein interaction mechanisms and their seminal importance in molecular biology. I was privileged that both Dr. Sancar and Dr. Paul Modrich (a Duke University professor who was also awarded the Nobel Prize in chemistry for discoveries in fundamental mechanisms of DNA repair) both served on my Ph.D. thesis committee. Such early encounters with and mentorship from expert scientists and my own experiences in Dr. Matson’s lab provided a solid foundation and opportunity for an adventurous expedition into molecular-genetic research.
Do you have advice or thoughts to share with current UNC-Chapel Hill graduate students?
Seek opportunity during your training by voraciously reading about your research topic and related areas as much as you can. Dr. Matson taught me the importance of critically reading the scientific literature, which also helped me to learn the craft of scientific writing. At the same time, I learned at Carolina to make the most of my graduate training by working hard in the lab, dedicating myself to turning over as many stones of investigation as I possibly could. I had some great mentors who not only guided me along the way but also encouraged me to think creatively and independently. So, I would advise today’s Carolina graduate students to take advantage of the vast wealth of knowledge afforded by the university’s professors and seize the unique opportunity by working passionately on a research topic that you find fascinating.