Chemotaxis Signal Section
Xuehua Xu, Ph.D.
Senior Associate Scientist, Chemotaxis Signal Section
Contact: For contact information, search the NIH Enterprise Directory.
Specialty(s): Allergy and Immunology, Infectious Disease, Pathology, Medical Microbiology
Major Areas of Research
- G protein-coupled receptor-mediated chemotaxis in the model organism Dictyostelium discoideum and mammalian neutrophils
- Phagocytosis and macropinocytosis in the organism Dictyostelium discoideum and mammalian leukocytes
- Functions of GPCRs in bacterial and viral infectious diseases
Program Description
Chemotaxis is directional cell migration guided by extracellular chemoattractant gradients. This cellular behavior of eukaryotic cells plays a critical role in many physiological processes, such as embryogenesis, neuron patterning, angiogenesis, innate immune responses to infections, metastasis of cancer cells, and the early development of the model organism Dictyostelium. Neutrophil senses and moves to inflammatory sites through chemotaxis, provides first-line host defense during pathogen invasion, and plays critical roles in both innate and adaptive immunity. Both Dictyostelium and neutrophil use G protein-coupled receptors (GPCRs) to sense and move toward higher concentrations of extracellular chemoattractants. One of Dr. Xu’s primary areas of research focuses on chemoattractant GPCR-mediated chemotaxis using both the model organism D. discoideum and mammalian neutrophils. Both Dictyostelium and neutrophils sense chemoattractant gradients over a huge concentration range through a cellular phenomenon known as adaptation. Combining computational simulation and experimental verification, Dr. Xu’s research proposed and identified locally recruited Ras inhibitors, C2GAP1 and CAPRI in Dictyostelium and human neutrophils, respectively, as essential players in GPCR-mediated Ras adaptation, gradient sensing, and cell sensitivity. Her discoveries suggest an evolutionarily conserved mechanism by which eukaryotic cells gate sensitive concentration ranges of chemoattractant for chemotaxis.
GPCRs, the largest groups of receptors in eukaryotic organisms, play pivotal roles in many processes closely related to human health and disease, including viral and bacterial infections, cancer, pain, cardiac problems, and asthma. Thus, GPCRs are prime targets in the development of treatments for many diseases in modern medicine. Dr. Xu has long-term research interests in GPCR functions in certain fundamental processes, such as human immunodeficiency virus (HIV) infections and phagocytosis of pathogens, with the ultimate goal of revealing novel therapeutic strategies for inflammation-related diseases.
Biography
Education
Ph.D., Tsukuba University, Japan
B.S., M.S., Harbin Normal University, China
Dr. Xuehua Xu obtained her bachelor’s and master’s degrees in biology from Harbin Normal University, China, and her Ph.D. in biotechnology from Tsukuba University, Japan. Starting in 2002, Dr. Xu had her postdoctoral training mentored by Dr. Tian Jin at the Laboratory of Immunogenetics (LIG), NIAID/NIH. Dr. Xu focused on developing and applying state-of-the-art imaging technologies to monitor the signaling network of GPCR-mediated chemotaxis in the model organism Dictyostelium discoideum. Interplay between computational simulation and experimental verification allowed her to propose a novel model, specifically a local inhibitory model, in GPCR-mediated chemotaxis to identify new components and novel signaling pathways essential for chemotaxis. In 2006, she was recruited as an assistant professor at the Georgetown University School of Medicine. She further expanded her research from the model organism to mammalian neutrophils and breast cancer. In 2010, she was recruited to NIH as a staff scientist in Dr. Jin’s group. She was promoted to Associate Scientist in 2019 and Senior Scientist in 2021.
Selected Publications
Xu X, Wen X, Moosa A, Bhimani S, Jin T. Ras inhibitor CAPRI enables neutrophil-like cells to chemotax through a higher-concentration range of gradients. Proc Natl Acad Sci U S A. 2021 Oct 26;118(43):e2002162118.
Xu X, Wen X, Veltman DM, Keizer-Gunnink I, Pots H, Kortholt A, Jin T. GPCR-controlled membrane recruitment of negative regulator C2GAP1 locally inhibits Ras signaling for adaptation and long-range chemotaxis. Proc Natl Acad Sci U S A. 2017 Nov 21;114(47):E10092-E10101.
Xu X, Gera N, Li H, Yun M, Zhang L, Wang Y, Wang QJ, Jin T. GPCR-mediated PLCβγ/PKCβ/PKD signaling pathway regulates the cofilin phosphatase slingshot 2 in neutrophil chemotaxis. Mol Biol Cell. 2015 Mar 1;26(5):874-86.
Xu X, Meckel T, Brzostowski JA, Yan J, Meier-Schellersheim M, Jin T. Coupling mechanism of a GPCR and a heterotrimeric G protein during chemoattractant gradient sensing in Dictyostelium. Sci Signal. 2010 Sep 28;3(141):ra71.
Xu X, Meier-Schellersheim M, Yan J, Jin T. Locally controlled inhibitory mechanisms are involved in eukaryotic GPCR-mediated chemosensing. J Cell Biol. 2007 Jul 2;178(1):141-53.
Xu X, Meier-Schellersheim M, Jiao X, Nelson LE, Jin T. Quantitative imaging of single live cells reveals spatiotemporal dynamics of multistep signaling events of chemoattractant gradient sensing in Dictyostelium. Mol Biol Cell. 2005 Feb;16(2):676-88.
Research Group
Dr. Xu’s group studies G protein-coupled receptors (GPCRs)’ signaling in chemotaxis of eukaryotic cell, metastasis of cancer cells, and viral infections, such as HIV infections and COVID-19.