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 lab has discovered and deeply characterized many human genetic differences that impact host-pathogen interactions and human disease susceptibility including variants near CXCL10 associated with CXCL10 levels and IBD risk (Wang et al. 2018), VAC14 regulating Salmonella invasion and typhoid fever risk through modulation of plasma membrane cholesterol (Alvarez et al. 2018), and MCOLN2 controlling Mg²⁺ levels to regulate Salmonella intracellular replication (Gibbs et al. 2023). The lab has expanded Hi-HOST from Salmonella and a single phenotype to eight pathogens and 79 phenotypes in the Hi-HOST Phenome Project and have made all this data available for browsing and download through our H2P2 web portal (Wang et al. 2018). Most recently, they developed a rapid next-generation Hi-HOST approach (scHi-HOST: single cell Hi-HOST) and successfully applied it to influenza A virus (IAV) and integrated the results with a human flu challenge study (Schott et al. 2022). Complementary to these studies of host genetic variation, the Ko lab also utilizes variation on the pathogen side to discover new effectors such as SarA (Jaslow et al. 2018; Gibbs et al. 2020) and regulators of virulence (Bourgeois et al. 2018; Bourgeois et al. 2021). These research endeavors have been made possible by continuous NIH funding since 2012 (K22, R01, R21, and U19 mechanisms). Dr. Ko's research innovation and achievements were recognized with the 2014 ICAAC Young Investigator Award, the 2018 ASM Merck Irving S. Sigal Memorial Award, and election to the American Society of Clinical Investigation in 2023.