Publications

P21 activated kinase 6 (PAK6) is a serine-threonine kinase with physiological expression enriched in the brain and overexpressed in a number of human tumors. While the role of PAK6 in cancer cells has been extensively investigated, the physiological function of the kinase in the context of brain cells is poorly understood. Our previous work uncovered a link between PAK6 and the Parkinson’s disease (PD)-associated kinase LRRK2, with PAK6 controlling LRRK2 activity and subcellular localization via phosphorylation of 14-3-3 proteins.

• Link: https://www.biorxiv.org/content/10.1101/2024.04.11.589075v1

Double cortin-like kinase 1 (DCLK1) exhibits high expression levels across various cancers, notably in human colorectal cancer (CRC). Diacerein, a clinically approved interleukin (IL)-1β inhibitor for osteoarthritis treatment, was evaluated for its impact on CRC proliferation and migration, alongside its underlying mechanisms, through both in vitro and in vivo analyses. The study employed MTT assay, colony formation, wound healing, transwell assays, flow cytometry, and Hoechst 33342 staining to assess cell proliferation, migration, and apoptosis.

• Link: https://www.sciencedirect.com/science/article/abs/pii/S1875536424606217?via%3Dihub

Weakly virulent environmental mycobacteria (EM) can cause severe disease in HLA-DRB1*15:02 or 16:02 adults harboring neutralizing anti-IFN-γ autoantibodies (nAIGAs). The overall prevalence of nAIGAs in the general population is unknown, as are the penetrance of nAIGAs in HLA-DRB1*15:02 or 16:02 individuals and the proportion of patients with unexplained, adult-onset EM infections carrying nAIGAs.

• Link: https://www.jci.org/articles/view/178263

Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers in urgent need of effective drugs. Echinatin, a natural compound extracted from Glycyrrhiza plants, exhibited promising anti-tumor effects. However, the efficacy and direct target of Echinatin in cSCC remain unclear.

• Link: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4745961

Immune-checkpoint inhibitors (ICIs) are increasingly used in the treatment of cancer, but they cause immune-related adverse events (irAEs) in around 40% of patients treated. Identifying biomarkers predictive of irAEs has become a priority for the optimal management of patients on ICIs. Herein, we review the state of the art regarding the most relevant biomarkers for predicting irAEs, distinguishing between biomarkers already clinically available and those under investigation. Although none of these biomarkers has been validated in prospective studies, there is growing evidence supporting their use for irAE prediction and clinical characterization, which depend on cancer type, ICI agent and organ affected by the toxicity. A better understanding of the pathogenic mechanisms underlying irAEs and the combination of different emerging biomarkers would allow us to improve the risk-benefit balance for patients who are candidates for ICI therapy.

• Link: https://www.mdpi.com/2072-6694/15/5/1629

We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre–α T cell receptor (pre-TCRα) expression. Low circulating naive αβ T cell counts at birth persisted over time, with normal memory αβ and high γδ T cell counts. Their TCRα repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue αβ T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive αβ T cell counts but high γδ T cell counts. Although residual pre-TCRα expression drove the differentiation of more αβ T cells, autoimmune conditions were more frequent in these patients compared with the general population.

• Link: https://www.science.org/doi/10.1126/science.adh4059#core-collateral-purchase-access

Postacute sequelae of COVID-19 (PASC), also referred to as “Long COVID”, sometimes follows COVID-19, a disease caused by SARS-CoV-2. Although SARS-CoV-2 is well known to promote a prothrombotic state, less is known about the thrombosis risk in PASC. Our objective was to evaluate platelet function and thrombotic potential in patients following recovery from SARS-CoV-2, but with clear symptoms of patients with PASC.

• Link: https://journals.sagepub.com/doi/10.1177/1358863X231224383

Hepatocellular carcinoma (HCC) has the highest mortality rate among malignant tumors worldwide. This study aimed to analyze the biological characteristics of serum proteins in hepatitis B (HBV)-related liver diseases, identify diagnostic biomarkers for HBV-infected HCC, and provide a scientific basis for its prevention and treatment.

• Link: https://www.sciencedirect.com/science/article/abs/pii/S0009898123005296?via%3Dihub

Hepatocellular carcinoma (HCC) has the highest mortality rate among malignant tumors worldwide. This study aimed to analyze the biological characteristics of serum proteins in hepatitis B (HBV)-related liver diseases, identify diagnostic biomarkers for HBV-infected HCC, and provide a scientific basis for its prevention and treatment.

• Link: https://www.sciencedirect.com/science/article/abs/pii/S0009898123005296?via%3Dihub

Nonalcoholic steatohepatitis (NASH) is a metabolism-associated fatty liver disease with accumulated mitochondrial stress, and targeting mitochondrial function is a potential therapy. The mitochondrial genome-encoded bioactive peptide MOTS-c plays broad physiological roles, but its effectiveness and direct targets in NASH treatment are still unclear. Here, we show that long-term preventive and short-term therapeutic effects of MOTS-c treatments alleviate NASH-diet-induced liver steatosis, cellular apoptosis, inflammation, and fibrosis. Mitochondrial oxidative capacity and metabolites profiling analysis show that MOTS-c significantly reverses NASH-induced mitochondrial metabolic deficiency.

• Link: https://www.cell.com/cell-reports/fulltext/S2211-1247(23)01599-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124723015991%3Fshowall%3Dtrue