Aleksandra Nita-Lazar, Ph.D.

Research in the Functional Cellular Networks Section focuses on understanding the changes that occur in the cell in response to exogenous factors such as pathogen- and symbiotic microbe-derived molecules, cytokines, and chemokines, which alter the differentiation state of cells in the immune system or whose production characterizes specific disease states. We are especially interested in large-scale absolute quantitative measurements of immune cell signaling cascade components, and we use a variety of experimental approaches (including but not limited to proteomics) to develop a systematic understanding of the inflammatory response of the innate immune cells to the acute and persistent signals they receive from the environment. Interestingly, many chronic inflammatory diseases occur due to an inappropriate immune response to subsets of commensal microbes and are driven by complex environmental, dietary, and genetic cues, which we are investigating using systems biology tools and aim to create predictive models of molecular interactions. The predictions of these models will, in turn, be employed to elucidate biological responses to stimuli at multiple scales of biological organization, including the cell, tissue, and, eventually, the whole organism.

The following are examples of our projects:

• Protein modifications involved in cell signaling: We map biologically important novel proteoforms, covalent PTMs, protein-protein interactions (PPIs), protein complexes with other molecules, and changes in subcellular localization which impact protein function and, in turn, the function of the innate immune cells. The protein and PTM levels are quantified in macrophages under varied but well-defined conditions. Examples of our interests include Toll-like receptor (TLR) signaling in macrophages, innate immune tolerance, exhaustion and memory, and long-term host-pathogen and host-microbiome interactions.
• Absolute quantification of molecular representation and interaction: Mathematical modeling of biological events is most reliable when the absolute quantities of molecules are known and used to set parameters in the simulations. Therefore, we are interested in absolute quantification of protein expression and protein-protein interactions. We have established the methodology for the lipid-induced signaling pathways involving the S1P1 and S1P2 receptors in monocyte/macrophage cell lineage-derived osteoclast precursors that control cell mobilization at bone surfaces, and, more recently, expanded it to the TLR signaling. We are currently working on the modeling of the signaling networks in the macrophages exposed to different microbe-derived ligands.

Special Interest Groups

• Systems Biology
• Immunology
• Proteomics
• Mass Spectrometry
• Glycobiology