Publications

HuProt Autoantibodies: The majority of patients treated with immune checkpoint inhibitors (ICIs) develop immune-related adverse events (irAE). It is currently not possible to predict the development of irAEs using biomarkers. Here we evaluated the IgG autoantibodies (AAbs) profile in pre-treatment sera of cutaneous metastatic melanoma patients treated with ICIs to identify AAbs that are associated with irAEs.

• Link: https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.9536?role=tab

ICBs revolutionized the treatment of advanced NSCLC patients but only a fraction of them obtain a response and clinical benefit from ICBs is often difficult to predict. Viral infections, whether acute, chronic or latent, have an impact on the immune system but their effect on ICBs efficacy is unknown. The aim of our study is to unveil the potential implications of antibody response to previous viral infections in predicting the response to ICBs in NSCLC patients.

• Link: https://www.annalsofoncology.org/article/S0923-7534(22)03047-2/fulltext#%20

To identify the specific diagnostic biomarkers related to pituitary adenomas (PAs), we performed serological antibody profiles for three types of PAs, namely Acromegaly, Cushing\'s and Nonfunctional Pituitary Adenomas (NFPAs), using the human proteome (HuProt) microarray. This is the first study describing the serum autoantibody profile of PAs.

• Link: https://onlinelibrary.wiley.com/doi/10.1002/prca.202100111

HuProt PPI: Spastin significantly influences microtubule regulation in neurons and is implicated in the pathogenesis of hereditary spastic paraplegia (HSP). However, post-translational regulation of the spastin protein remains nebulous. The association between E3 ubiquitin ligase and spastin provides a potential therapeutic strategy.

• Link: https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-022-00851-1

HuProt Autoantibodies: A molecular mimicry between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human proteins supports the possibility that autoimmunity takes place during coronavirus disease 2019 (COVID-19) contributing to tissue damage. For example, anti-phospholipid antibodies (aPL) have been reported in COVID-19 as a result of such mimicry and thought to contribute to the immunothrombosis characteristic of the disease. Consistently, active immunization with the virus spike protein may elicit the production of cross-reactive autoantibodies, including aPL.

• Link: https://www.frontiersin.org/articles/10.3389/fimmu.2022.930074/full

HuProt Autoantibodies: Autoantibody (AAb) has a prominent role in prostate cancer (PCa), with few studies profiling the AAb landscape in Chinese patients. Therefore, the AAb landscape in Chinese patients was characterized using protein arrays. First, in the discovery phase, Huprot arrays outlined autoimmune profiles against ~ 21,888 proteins from 57 samples. In the verification phase, the PCa-focused arrays detected 25 AAbs selected from the discovery phase within 178 samples. Then, PCa was detected using a backpropagation artificial neural network (BPANN) model. In the validation phase, an enzyme-linked immunosorbent assay (ELISA) was used to validate four AAb biomarkers from 196 samples.

• Link: https://link.springer.com/article/10.1007/s00262-022-03242-0

HuProt Antibody Specificity: Affinity matured self-reactive antibodies are found in autoimmune diseases like systemic lupus erythematous. Here we used fate-mapping reporter mice and single cell transcriptomics coupled to antibody repertoire analysis to characterize the post-germinal center (GC) B cell compartment in a new mouse model of autoimmunity. Antibody secreting cells (ASCs) and memory B cells (MemBs) from spontaneous GCs grouped into multiple subclusters. ASCs matured into two terminal clusters, with distinct secretion, antibody repertoire and metabolic profiles. MemBs contained FCRL5+ and CD23+ subsets, with different in vivo localization in the spleen.

• Link: https://www.biorxiv.org/content/10.1101/2022.06.21.496939v1

Poly(ADP-ribose) (PAR) plays a crucial role in intracellular signaling and scaffolding through covalent modification or non-covalent binding to target proteins. The non- covalent binding PARylome has not been extensively characterized. Here we performed a PAR-binding screen using a human protein microarray that covers most of the human proteome to characterize the non-covalent binding PARylome. A total of 356 PAR- binding proteins were identified.

• Link: https://www.biorxiv.org/content/10.1101/2022.06.06.494829v1

HuProt Small Molecule: Sepsis-induced inflammatory response leads to intestinal damage and secondary bacterial translocation, causing systemic infections and eventually death. Emodin is a natural anthraquinone derivative in many plants with promising bioactivities. However, the effects and mechanisms of emodin on sepsis-induced intestinal dysfunctions have not been well clarified yet. We found that emodin treatment suppressed the inflammatory response in the intestines of septic mice. Intestinal barrier function was also improved by emodin through enhancing ZO-1 and occludin expression, which prevented the secondary translocation of Escherichia coli.

• Link: https://www.hindawi.com/journals/mi/2022/5026103/

HuProt Enzyme: WWP2 is a HECT E3 ligase that targets protein Lys residues for ubiquitination and is comprised of an N-terminal C2 domain, four central WW domains, and a C-terminal catalytic HECT domain. The peptide segment between the middle WW domains, the 2,3-linker, is known to autoinhibit the catalytic domain, and this autoinhibition can be relieved by phosphorylation at Tyr369. Several protein substrates of WWP2 have been identified, including the tumor suppressor lipid phosphatase PTEN, but the full substrate landscape and biological functions of WWP2 remain to be elucidated.

• Link: https://www.jbc.org/article/S0021-9258(22)00294-0/fulltext#%20