A5052399625- Connective tissue disorders research
- Lysosomal Storage Disorders Research
- Coronary Artery Anomalies
- Aortic aneurysm repair treatments
- Calcium signaling and nucleotide metabolism
- Dermatological and Skeletal Disorders
- Congenital heart defects research
- Cardiovascular Issues in Pregnancy
- Cellular transport and secretion
- Aortic Disease and Treatment Approaches
- MicroRNA in disease regulation
- Adenosine and Purinergic Signaling
- Connexins and lens biology
- Congenital Heart Disease Studies
- Sphingolipid Metabolism and Signaling
- Neuroscience and Neuropharmacology Research
- Neurological Complications and Syndromes
- Genetics and Neurodevelopmental Disorders
- Extracellular vesicles in disease
- Hip disorders and treatments
- Blood Coagulation and Thrombosis Mechanisms
- Research on Leishmaniasis Studies
- Poisoning and overdose treatments
- Genomics and Rare Diseases
- BRCA gene mutations in cancer
Clínica Alemana
2015-2025
Universidad del Desarrollo
2015-2025
Johns Hopkins University
2012-2025
Johns Hopkins Medicine
2012-2025
Emory University
2023
Paradise Valley Hospital
1986
Loeys-Dietz syndrome (LDS) is a connective tissue disorder that characterized by high risk for aneurysm and dissection throughout the arterial tree phenotypically resembles Marfan syndrome. LDS caused heterozygous missense mutations in either TGF-β receptor gene (TGFBR1 or TGFBR2), which are predicted to result diminished signaling; however, aortic surgical samples from patients show evidence of paradoxically increased signaling. We generated 2 knockin mouse strains with Tgfbr1 Tgfbr2...
The aortic root is the predominant site for development of aneurysm caused by heterozygous loss-of-function mutations in positive effectors transforming growth factor-β (TGF-β) pathway. Using a mouse model Loeys-Dietz syndrome (LDS) that carries kinase-inactivating mutation TGF-β receptor I, we found effects this depend on lineage origin vascular smooth muscle cells (VSMCs). Secondary heart field–derived (SHF-derived), but not neighboring cardiac neural crest–derived (CNC-derived), VSMCs...
Aortic dissection or rupture is a major cause of mortality in vascular Ehlers-Danlos Syndrome (vEDS), connective tissue disorder caused by heterozygous mutations the COL3A1 gene. C57BL6/J (BL6) mice carrying Col3a1 G938D/+ mutation recapitulate vEDS phenotype and die suddenly aortic rupture/dissection. However, 129S6/SvEvTac (129) expressing same show near-complete life-long protection from rupture. To identify genetic modifiers risk vEDS, we performed genome-wide genotyping intercrossed...
Vascular Ehlers-Danlos syndrome (vEDS) is an autosomal-dominant connective tissue disorder caused by heterozygous mutations in the COL3A1 gene, which encodes pro-α 1 chain of collagen III. Loss structural integrity extracellular matrix believed to drive signs and symptoms this condition, including spontaneous arterial dissection and/or rupture, major cause mortality. We created 2 mouse models vEDS that carry Col3a1 encode glycine substitutions analogous those found patients, we showed...
Niemann-Pick type C (NPC) disease, caused by mutations in the NPC1 or NPC2 genes, disrupts cellular cholesterol and glycolipids trafficking. Patients exhibit a wide spectrum of visceral neurological manifestations, suggesting role for genomic modifiers. To uncover genetic basis NPC resilience, we analyzed exomes an family with diverse phenotypes, from very mild to severe involvement. Linkage analysis revealed loss-of-function (LOF) variants CCDC115, SLC4A5, DEPDC5, ETFDH, SNRNP200, DOCK1...
Oncogenes drive cancer progression, but few are active exclusively in tumor cells. Connexins (Cxs), traditionally recognized as ion channel proteins, can localize to the nucleus and regulate gene expression, playing key roles both physiological pathological processes. Cx46, once thought be restricted eye lens, has been implicated growth, though its underlying mechanisms remain unclear. This study investigates nuclear presence of Cx46 cells potential role a transcriptional modulator. We...
Abstract Rare diseases (RDs) are a large number of diverse conditions with low individual prevalence, but collectively may affect up to 3.5–5.9% the population. They have psychosocial and economic impact on patients societies, significant problem for healthcare systems, especially countries limited resources. In Chile, financial protection exists 20 known RDs through different programs that cover diagnosis treatments. Although beneficial conditions, most RD left without proper legal...
// Helga Weber 1, 2, * , José R. Valbuena 3, Mustafa A. Barbhuiya 4 Stefan Stein 5 Hana Kunkel Patricia García 6 Carolina Bizama Ismael Riquelme 2 Jaime Espinoza 7 Stephen E. Kurtz 8 Jeffrey W. Tyner Juan Francisco Calderon 9 Alejandro H. Corvalán 6, 10 Manuel Grez Akhilesh Pandey 4, 11 Pamela Leal-Rojas 1 C. Roa Center of Excellence in Traslational Medicine (CEMT) and Scientific Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco, Chile Department Pathology,...
The global dissemination of methicillin-resistant Staphylococcus aureus (MRSA) is associated with the emergence and establishment clones in specific geographic areas. Chilean-Cordobes clone (ChC) (ST5-SCC
Patients with chromosome 22q11 deletion syndrome exhibit significant phenotypic variability. Epidemiologic data suggest a higher incidence in Hispanics, but limited clinical information is available from Latin-American patients. We describe the features of Chilean patients and compare their findings those reported large European, Japanese US series. Data were obtained 208 five medical centers. Mean age at diagnosis was 5.2 years, median 2.3 years. Congenital heart defects present 59.6%,...
The COVID-19 plague is hitting mankind. Several viruses, including SARS-CoV-1, MERS-CoV, EBOV, and SARS-CoV-2, use the endocytic machinery to enter cell. Genomic variants in NPC1, which encodes for endo-lysosomal Niemann-Pick type C1 protein, restricts host-range of viruses bats susceptibility infections humans. Lack NPC1 its pharmacological suppression inhibits many viral SARS-CoV-1 Type I Feline Coronavirus Infection. Antiviral effects NPC1-inhibiting drugs treatment should be explored.
Connexin (Cxs) hemichannels participate in several physiological and pathological processes, but the molecular mechanisms that control their gating remain elusive. We aimed at determining role of extracellular cysteines (Cys) function Cx46 hemichannels. studied mutated all its Cys to alanine (Ala) (one a time) effects mutations on expression, localization, hemichannel activity. Wild-type mutants were expressed comparable levels, with similar cellular localization. However, functional...
Microdeletion 22q11 in humans causes velocardiofacial and DiGeorge syndromes.Most patients share a common 3Mb deletion, but the clinical manifestations are very heterogeneous.Congenital heart disease is present 50-80% of significant cause morbidity mortality.The phenotypic variability suggests presence modifiers.Polymorphisms VEGFA gene, coding for vascular endothelial growth factor A, have been associated with non-syndromic congenital disease, as well cardiovascular anomalies microdeletion...
Identification of genetic modulators lysosomal enzyme activities and glycosphingolipids (GSLs) may facilitate the development therapeutics for diseases in which they participate, including Lysosomal Storage Disorders (LSDs). To this end, we used a systems genetics approach: measured 11 hepatic enzymes many their natural substrates (GSLs), followed by modifier gene mapping GWAS transcriptomics associations panel inbred strains. Unexpectedly, most GSLs showed no association between levels...
The acid β-glucocerebrosidase (GCase) enzyme cleaves glucosylceramide into glucose and ceramide. Loss of function variants in the gene encoding for GCase can lead to Gaucher disease Parkinson's disease. Therapeutic strategies aimed at increasing activity by targeting a modulating factor are attractive poorly explored. To identify genetic modifiers, we measured hepatic 27 inbred mouse strains. A genome-wide association study (GWAS) using as trait identified several candidate modifier genes,...
Marfan Syndrome (MFS) is an autosomal dominant condition caused by variants in the fibrillin-1 (FBN1) gene. Cardinal features of MFS include ectopia lentis (EL), musculoskeletal and aortic root aneurysm dissection. Although dissection ascending aorta main cause mortality MFS, clinical course differs considerably age onset severity, even among individuals who share same causative variant, suggesting existence additional genetic that modify severity cardiovascular phenotype MFS. We recruited...