Yongna Xing

Credentials: Oncology Department

Position title: Cell signaling related to caner, structural biology, biochemistry, proteomics

Email: xing@oncology.wisc.edu

Phone: (608) 262-8376

Address:
6451 Wi Institute Medical Research
1111 Highland Ave
Madison, WI 53705

Headshot

lab website:

https://mcardle.wisc.edu/who-we-are/mcardle-faculty/yongna-xing-phd

focus groups:

Cancer Biology; Systems Biology

research description:

The Xing lab is interested in elucidating the molecular, structural and biochemical basis of diverse cell signaling pathways and regulations related to cancer, neurological disorder and toxicity, such as phosphatase regulation and aryl hydrocarbon receptor (AHR) signaling. We utilize diverse multi-disciplinary biophysical, biochemical, bioinformatics, and cell biology approaches, including x-ray crystallography, cryo-electron microscopy, computational structural biology, enzymology, the state-of-the-art proteomics, bioinformatics and time-lapse fluorescent imaging, to gain deep mechanistic understanding and facilitate identification of novel therapeutic targets and strategies.

Protein phosphatase 2A (PP2A) is one of the most important and abundant Ser/Thr phosphatases in all eukaryotic cells with complex regulation and compositions. It plays a critical role in many essential aspects of cellular function, and deregulation of its function has been linked to many types of cancer, neurodegenerative disorders, and heart failure. PP2A participates in diverse cellular processes via formation of ~100 heterotrimeric holoenzymes. We made critical contributions to the understanding of the broad structural basis of PP2A core enzyme, holoenzymes and regulation complexes, and developed a plethora of research tools that allow us to reconstitute and dissect the biochemical processes involved in diverse aspects of PP2A regulation and substrate recognition. Our ongoing research involves a highly dynamic aspect of PP2A regulation that is crucial for tight control of PP2A holoenzyme biogenesis, disassembly, and activity. We also have critical efforts toward identifying interaction motifs for diverse PP2A holoenzymes and characterizing biochemical codes for PP2A holoenzyme-substrate interactions that can be described in computer language for bioinformatic search. Built on a highly multidisciplinary research with broad research strategies, including biochemistry, cell biology, system biology, cryo-EM, x-ray crystallography and cancer bioinformatics, we aim to rapidly predict and test phosphatase action in diverse signaling networks and disease mutations that alter phosphatase function in multiple types of cancer, neurological disorders and rare genetic diseases.

Aryl hydrocarbon receptor (AHR) is a PAS family transcription factor that mediates cellular responses to diverse environmental chemicals and endogenous metabolites. It plays an important role in toxicity response, and normal immune and cardiovascular functions, with important implication for cancer and autoimmune diseases. Our ongoing research is built on our recent breakthroughs on the crystal structure of AHR signaling complex and AHR ligand chemistry in which we identified trace derivatives from cellular metabolite, kynurenine, as potent AHR ligands, which we named TEACOPs (trace elongated aromatic condensation products of kynurenine). Our research aim to decipher how kynurenine/TEACOPs and environmental compounds differentially activate AHR signaling and differentially modulate the functions of diverse immune cells to provide insights for diverse inflammatory diseases and cancer. We also aim to elucidate the structural basis underlying the dichotomy of AHR signaling using single particle cryo-EM.

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