Publications

Decidualization of human endometrial stromal cells (hESCs) is essential for the maintenance of pregnancy, which depends on the fine-tuned regulation of hESCs survival, and its perturbation contributes to pregnancy loss. However, the underlying mechanisms responsible for functional deficits in decidua from recurrent spontaneous abortion (RSA) patients have not been elucidated. Here, we observed that JAZF1 was significantly downregulated in stromal cells from RSA decidua. JAZF1 depletion in hESCs resulted in defective decidualization and cell death through apoptosis.

• Link: https://www.nature.com/articles/s42003-023-04931-x

Glycolysis is essential for the classical activation of macrophages (M1), but how glycolytic pathway metabolites engage in this process remains to be elucidated. Glycolysis leads to production of pyruvate, which can be transported into the mitochondria by the mitochondrial pyruvate carrier (MPC) followed by utilization in the tricarboxylic acid cycle. Based on studies that used the MPC inhibitor UK5099, the mitochondrial route has been considered to be of significance for M1 activation. Using genetic approaches, here we show that the MPC is dispensable for metabolic reprogramming and activation of M1 macrophages.

• Link: https://www.nature.com/articles/s42255-023-00800-3

Immune checkpoint inhibitors that overcome T cell suppressive mechanisms in tumors have revolutionized the treatment of cancer but are only efficacious in a small subset of patients. Targeting suppressive mechanisms acting on innate immune cells could significantly improve the incidence of clinical response by facilitating a multi-lineage response against the tumor involving both adaptive and innate immune systems. Here, we show that intra-tumoral interleukin (IL)-38 expression is a feature of a large frequency of head and neck, lung and cervical squamous cancers and correlates with reduced immune cell numbers. We generated IMM20324, an antibody that binds human and mouse IL-38 proteins and inhibits the binding of IL-38 to its putative receptors, interleukin 1 receptor accessory protein-like 1 (IL1RAPL) and IL-36R.

• Link: https://www.tandfonline.com/doi/full/10.1080/19420862.2023.2212673?src=

Understanding why individuals with Down syndrome are highly predisposed to autoimmunity has broad mechanistic and therapeutic implications. New work identifies novel potential mechanistic pathways driving increased autoimmunity-relevant CD11c+ B cells and provides the broadest view to date of the repertoire of autoantibodies generated in individuals with Down syndrome.

• Link: https://www.nature.com/articles/s41584-023-00970-0

HuProt Antibody Specificity: Despite recent advances in cancer treatments, pancreatic cancer has a dismal prognosis globally. Early detection of cancer cells and effective treatments for recalcitrant tumors are required, but the innovative therapeutic tools remain in development. Cancer-specific antigens expressed only on cancer cells may help resolve these problems, and antibodies to such antigens have potential in basic research and clinical applications. To generate specific antibodies that bind to proteins expressed on the surface of pancreatic cancer cells, we immunized mice with human pancreatic cancer MIA PaCa-2 cells, and isolated a hybridoma that produces a monoclonal antibody (mAb), named 12–13.8.

• Link: https://www.sciencedirect.com/science/article/pii/S0300908423000020?via%3Dihub

HuProt PPI: Mutations in the LMNA gene encoding Lamin A and C (Lamin A/C), major components of the nuclear lamina, cause laminopathies including dilated cardiomyopathy (DCM), but the underlying molecular mechanisms have not been fully elucidated. Here, by leveraging single-cell RNA sequencing (RNA-seq), assay for transposase-accessible chromatin using sequencing (ATAC-seq), protein array, and electron microscopy analysis, we show that insufficient structural maturation of cardiomyocytes owing to trapping of transcription factor TEA domain transcription factor 1 (TEAD1) by mutant Lamin A/C at the nuclear membrane underlies the pathogenesis of Q353R-LMNA–related DCM.

• Link: https://www.science.org/doi/10.1126/sciadv.ade7047

HuProt Autoantibodies: Circulating biomarkers for the identification of patients with “actionable” nodules may increase screening uptake and decrease false-positive rates associated with low-dose computed tomography (LDCT). Novel autoantibody biomarkers were identified utilizing a HuProt™ protein microarray. Luminex assays were developed for the targeted measurement of identified biomarkers within a large Biomarker Development Cohort (n = 841). Each individual biomarker’s performance was assessed. The Biomarker Development Cohort was split into three separate cohorts: Training, Validation 1, and Validation 2. Utilizing a Training cohort, a random forest model for identifying patients with “actionable” nodules from those with “non-actionable” nodules was built.

• Link: https://www.mdpi.com/2072-6694/15/8/2259

Lung cancer is the leading cause of cancer death in most countries. Although early diagnosis and treatment critically influence prognosis, lung cancers are generally only discovered in the late stages of the disease. Widely-used screening and diagnostic methods are not suitable for preventive screening, and high-throughput technologies based on serum biomarkers are needed.

• Link: https://www.eurekaselect.com/article/123880

Kawasaki disease (KD), a rare multisystem inflammatory condition that predominantly affects children under six years of age, is the leading cause of childhood-acquired heart disease in developed countries. The pathogenesis is unknown, but studies support that an infectious stimulus triggers an autoimmune reaction in a genetically susceptible child. Recent studies demonstrated an association with autoantibody response to Del-1 (also known as EDIL3) in children with KD. Del-1 is an extracellular matrix protein that is expressed both in macrophages and vascular endothelium.

• Link: https://www.sciencedirect.com/science/article/abs/pii/S0165247823000512?via%3Dihub

We measured brain injury markers, inflammatory mediators, and autoantibodies in 203 participants with COVID-19; 111 provided acute sera (1-11 days post admission) and 56 with COVID-19-associated neurological diagnoses provided subacute/convalescent sera (6-76 weeks post-admission). Compared to 60 controls, brain injury biomarkers (Tau, GFAP, NfL, UCH-L1) were increased in acute sera, significantly more so for NfL and UCH-L1, in patients with altered consciousness. Tau and NfL remained elevated in convalescent sera, particularly following cerebrovascular and neuroinflammatory disorders.

• Link: https://www.medrxiv.org/content/10.1101/2023.04.03.23287902v1