Dennis Ko, MD, PhD – Biography

Associate Professor

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Dennis Ko received a B.S. from Cornell University in 1997. His research career began in the lab of Dr. Jeffrey W. Roberts at Cornell University. Using a genetic screen of the bacterial initiation factor σ70 followed by biochemical characterization, he identified a surface on the protein important for transcriptional regulation by the phage Q protein and revealed a novel role for a sigma factor beyond transcription initiation.

His training continued from 1997-2005 in the MSTP at Stanford University. He completed both MD and PhD degrees but clearly saw that his future was in research aimed at understanding the biology of disease. His thesis project was carried out in the laboratory of Dr. Matthew P. Scott. Using a combination of biochemistry, cell biology, genetics and animal models, he pioneered a new subject in the lab examining how genetic alterations lead to the neurodegenerative lipid disorder, Niemann-Pick type C (NPC). The main findings of his studies on NPC were that: 1) mutation of NPC1 slowed the dynamic trafficking of the organelles in which it is found, contributing to the lipid derangements seen in this disorder; 2) NPC2 binds cholesterol with sub-micromolar affinity, and this binding is essential for activity; and 3) the requirement of NPC1 in the brain is cell autonomous, and its loss can lead to neuronal cell death with properties consistent with autophagy.

He took a year off for personal reasons following the completion of his MD/PhD degrees in June 2005. During this time, he volunteered in two labs on an informal basis to remain scientifically engaged. It was during this time that he decided to switch fields. Two major developments helped shape this decision: 1) the massive amount of genetic information from studies of human diversity and 2) improvements in studying mammalian cell biology, especially RNA interference and fluorescence assays. He, therefore, decided to engage in studies that would take advantage of these new developments in the field of host-pathogen interactions.

As a post-doctoral Life Sciences Research Foundation fellow in the lab of Samuel Miller at the University of Washington, Dr. Ko developed a novel screening method termed Hi-HOST (high throughput human in vitro susceptibility testing) for identifying human genetic variation that affects cell-based readouts of bacterial infection. Using this approach, he measured cellular variation in the human cell death response to Salmonella and identified common genetic differences that influence this in vitro trait. Through this approach, he was able to both discover unexpected cell biology and identify genetic differences important for human health and disease.

Dr. Ko joined the faculty of Duke Molecular Genetics & Microbiology, Medicine, and the Center for Human Genome Variation in 2012. His laboratory will continue applying the Hi-HOST approach to host-pathogen traits for Salmonellae, Yersinia, and other cellular phenotypes of infection and inflammation. The long-term goal of the research is to fully understand the human genetic variation for traits important for bacterial pathogenesis and how they impact human disease.