Valerie P. O'Brien
Ph.D. – Washington University in St. Louis, 2017
Postdoc – Fred Hutchinson Cancer Center, 2018 – 2023
Currently Accepting Students
Bacterial-driven tissue remodeling
Chronic bacterial infections are common at a variety of body sites, such as the stomach, bladder and lung. Although a healthy immune system should clear infections and prevent recurrent episodes, some bacteria can subvert host immunity and establish long-lasting infections. Chronic bacterial infections can trigger maladaptive tissue remodeling, directly resulting in other diseases such as epithelial cancers. My research program investigates this paradigm using clinically relevant mouse models coupled with studies of human samples to mechanistically dissect maladaptive tissue remodeling caused by chronic bacterial infections.
My primary model system is gastric cancer, most cases of which can be attributed to stomach infection with the bacterium Helicobacter pylori (Hp). Hp elicits inflammation that drives gastric tissue changes, leading to cancer. Because Hp infects half the world, gastric cancer is one of the most common cancers globally, but how chronic Hp infection and inflammation cause gastric cancer is not well understood. My research program leverages bacterial and immune profiling, scRNA-seq, therapeutic interventions and complementary studies in mouse models and human samples to yield critical insight into how and why Hp is able to establish chronic infection that maladaptively remodels the gastric tissues to cause disease. Our long-term goal is to develop new host-targeted therapies for gastric cancer.
NIH/NCI K99/R00 Pathway to Independence Award (PI: O’Brien), K99CA263036
O’Brien VP*, Jackson LK*, Frick JP, Rodriguez Martinez AE, Jones DS, Johnston CD, Salama NR. Helicobacter pylori chronic infection selects for effective colonizers of metaplastic glands. mBio 2023 e0311622. *Equal contributors.
O’Brien VP, Koehne A, Dubrulle J, Rodriguez AR, Leverich CK, Kong P, Campbell JS, Pierce RH, Goldenring JR, Choi E, Salama NR. Sustained Helicobacter pylori infection accelerates gastric dysplasia in a mouse model. Life Science Alliance 2020 4(2):e202000967.
O’Brien VP, Dorsey D, Hannan TJ, Hultgren SJ. Host restriction of Escherichia coli recurrent urinary tract infection occurs in a bacterial strain-specific manner. PLOS Pathogens 2018 14(12): e1007457.
O’Brien VP, Hannan TJ, Yu L, Livny J, Roberson EDO, Schwartz DJ, Souza S, Mendelsohn C, Colonna M, Lewis AL, Hultgren SJ. A mucosal imprint left by prior Escherichia coli bladder infection sensitizes to recurrent disease. Nature Microbiology 2016 2:16196.
Complete list of Dr. O’Brien’s publications at NCBI: link