Articles

Signal Transduction and Targeted Therapy: PAK1 is a broad-spectrum anti-SARS-CoV-2 target

Signal Transduction and Targeted Therapy: PAK1 is a broad-spectrum anti-SARS-CoV-2 target

Yuxia Zhang
22 October 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has had a significant impact on healthcare systems and economies worldwide. The emergence of new viral strains represents a major challenge in the development of effective antiviral agents. The spike protein of SARS-CoV-2 interacts with ACE2 on the cell surface, facilitating viral attachment and entry. Spike protein also promotes ACE2 degradation, but the molecular mechanisms are not fully determined. In this study, Dr. Ming Liu et al from our laboratory showed that the spike-ACE2 complex is endocytosed and degraded via autophagy, in a manner that depends on clathrin-mediated endocytosis and PAK1-mediated cytoskeleton rearrangement. Importantly, through collaboration with ...read more

Nature Cardiovascular Research: MCM8-mediated mitophagy protects vascular health in response to nitric oxide signaling

Nature Cardiovascular Research: MCM8-mediated mitophagy protects vascular health in response to nitric oxide signaling

Yuxia Zhang
03 September 2023

Kawasaki disease (KD) is a systemic vasculitis mainly affects children under 5 years of age. If untreated, sudden death may occur due to coronary artery aneurysms. KD incidences vary among different populations, being highest among East Asian and lowest among Caucasian ethnic groups. But the underlying genetic mechanism is not fully understood. Dr. Meng Lin et.al from our laboratory discovered that children with KD who developed coronary artery aneurysms had decreased expression of the minichromosome maintenance protein MCM8 and increased activation of type I interferon signaling compared with healthy control subjects. By creating a Mcm8 knockout mice, Meng went on to discover that it was mtDNA that were accumulated in the cytosol ...read more

Pathological Jaundice

Pathological Jaundice

Yuxia Zhang
09 October 2021

Jaundice is caused by too much bilirubin, a breakdown product of red blood cells. After being processed in the liver, bilirubin is passed out of body in poo. Newborn babies have a high number of red blood cells that are broken down and replaced frequently. Their livers are less effective in removing it from the blood. Jaundice therefore occurs in most of newborn babies. Jaundice often corrects itself by the time a baby is around 2 weeks old when the body produces less bilirubin and the liver is more effective at removing it from the body. When jaundice is persistent (pathological jaundice), it may indicate underlying health conditions that need to be treated. Some causes of pathological jaundice include: ...read more

Biliary Atresia

Biliary Atresia

Yuxia Zhang
12 September 2021

Biliary Atresia (BA) affects one in every 5,000-18,000 newborns. Perinatal infection is a significant trigger, which can cause obstruction of the extrahepatic bile duct and rapid liver failure. Surgical removal of the duct remnants followed by hepatoportoenterostomy (Kasai’s procedure) is required after diagnosis. If left untreated, Biliary Atresia progression to end-stage cirrhosis usually occurs within one year. Following the Kasai’s operation, approximately 50% of the Biliary Atresia patients will require liver transplantation within the first 2 years of life, while the remainder children surviving with the native livers will suffer long-term complications including repeated cholangitis, portal hypertension, esophageal variceal bleeding, and hepatic osteodystrophy. At Pediatric Immunity and Healthcare, we have been developing biomarkers and therapies that may improve the ...read more

Hirschsprung's Disease

Hirschsprung

Yuxia Zhang
12 August 2021

Hirschsprung's disease (HSCR) is a developmental disorder caused by the failure of enteric neural crest-derived cells (ENCC) to colonize the entire gut, leading to absence of neurons from variable lengths of the colon. Hirschsprung disease usually start in very young children, but may also occur later. The symptoms involve constipation, vomiting, abdominal pain or swelling, diarrhea, poor feeding, malnutrition, jaundice and slow growth. There are two main types of Hirschsprung disease, known as short-segment disease and long-segment disease, defined by the region of the intestine lacking nerve cells (aganglionic segments). Although mutations in several genes may cause HSCR, majority of cases occur in a sporadic manner. The treatment involves surgical removing the aganglionic intestinal ...read more

Food Allergy, Colitis and Inflammatory Bowel Disease

Food Allergy, Colitis and Inflammatory Bowel Disease

Yuxia Zhang
29 July 2021

Food allergy, colitis and IBD are developmentally related gastrointestinal inflammatory diseases affecting one in every 10 children. It is generally accepted that genetic and environmental factors are both involved. Our scientific partners studied cohorts of children with food allergy, colitis and IBD by incorporating single-cell RNA sequencing, whole genome-wide association study (GWAS) and immunological profiling. They discovered that hyper-inflammation is a common feature of food allergy, colitis and IBD, while deficit in cAMP response pathways, NLRP3-R779C mutation, and genetic instability are some of the underlying mechanisms. At Pediatric Immunity and Healthcare we have been developing biomarkers and treatments that help to achieve precision therapy. ...read more

Cell: Liver immune profiling reveals pathogenesis and therapeutics for biliary atresia

Cell: Liver immune profiling reveals pathogenesis and therapeutics for biliary atresia

Yuxia Zhang
06 July 2021

An important function of the fetal liver is hematopoiesis (generation of red cells and immune cells), which peaks around 7-17 post conception weeks (PCWs). After 20 PCWs, bone marrow takes over the majority of the hematopoiesis function. In bone marrow, progenitor B cells undergo processes that eliminate B cell receptors that have high affinity to body's self-molecules. Defects in establishing B cell tolerance can cause autoimmune diseases that target and destroy body's self-tissues. Perinatal infection has been associated with the development of biliary atresia (BA), an autoimmune liver disease that can cause rapid liver failure in infants. The pathogenic mechanisms occurring locally in the liver of infants with BA was incompletely understood. ...read more

Cell: Pediatric Onset Colitis and Inflammatory Bowel Disease

Cell: Pediatric Onset Colitis and Inflammatory Bowel Disease

Yuxia Zhang
28 June 2021

Pediatric onset colitis and inflammatory bowel disease (IBD) represent significant challenges to many infants, children and their guardians. Disease etiopathogenesis remains incompletely understood, and up to 50% children do not respond effectively to conventional therapy (JAMA Pediatr. 2015 Nov;169(11):1053-60. doi: 10.1001/jamapediatrics.2015.1982.).In collaboration with Prof. Fan Bai from Peking University, we performed scRNA sequencing and immune profiling on the colonic mucosae and discovered deficiency of CD39-expressing intraepithelial T cells (CD39+ IETs) in children with colitis or IBD. We hypothesized that this deficiency may lead to accumulation of ATP and ADP, which will subsequently escalate colonic inflammation through activation of macrophages and platelets, respectively. Indeed, platelet dysfunction has long been recognized and perused in ...read more

Risk Genetic Variants in Children With Immune-Related Illness

Risk Genetic Variants in Children With Immune-Related Illness

Yuxia Zhang
28 June 2021

The relatively naïve and immature immune system from infants and children face numerous challenges in everyday life. The suspicion or diagnosis of primary immunodeficiency (PID), autoinflammatory disease (AID), Chrohn's disease (CD), Ulcerative colitis (UC), systemic lupus erythematosus (SLE) can be devastating to the families. Many of these pediatric-onset illness have significant underlying genetic contributions. Identification of compound heterozygous variants of recessive genes, X-linked variants in boys, and de novo variants may provide definitive diagnosis and inform precision treatment. Through the generous sponsorship of Guangzhou Women and Children's Medical Center, we perform whole exome sequencing (WES) and bioinformatic analysis for affected children, their siblings and parents. We have helped with diagnosis of child ...read more

Biliary Atresia: A Forgotten Killer Affecting 1 in 5000 Infants

Biliary Atresia: A Forgotten Killer Affecting 1 in 5000 Infants

Yuxia Zhang
28 June 2021

Jaundice is common in newborns. However, for up to one in every 5000 newborns, Jaundice may never go away and children develop Biliary Atresia (BA) (Hartley et al., 2009). The cause of Biliary Atresia is not entirely clear, both developmental defects or perinatal infections can cause obstructions of the extrahepatic bile ducts and result in rapid liver failure in early infancy (Lakshminarayanan and Davenport, 2016). Surgical removal of the duct remnants followed by hepatoportoenterostomy (Kasai's procedure) is required after diagnosis, (Hopkins et al., 2017). If left untreated, Biliary Atresia progression to end-stage cirrhosis usually occurs within one year. Following the Kasai's operation, approximately 50% of the Biliary Atresia patients will require liver ...read more

Liver Cirrhosis, Hepatocellular Carcinoma and Cholangiocarcinoma

Liver Cirrhosis, Hepatocellular Carcinoma and Cholangiocarcinoma

Ming Liu
08 June 2021

Cirrhosis is a late-stage liver disease in which healthy liver tissue is replaced with scar tissue and the liver is permanently damaged. Many types of liver diseases and conditions injure healthy liver cells, causing cell death and inflammation. It is widely accepted that long-term inflammation will eventually induce liver cancer, of which HCC is the most common type. HCC ranks the fifth most prevalent cancers in the world and is the third leading cause of cancer deaths, with approximately 400,000 newly diagnosed patients every year in China. Lack of suitable biomarkers for early detection and limited treatment strategies are the major causes of high mortality. The emergence of immune checkpoint inhibitors such as monoclonal ...read more