A5103213827- Renal and related cancers
- Tuberous Sclerosis Complex Research
- Circadian rhythm and melatonin
- Muscle Physiology and Disorders
- Mesenchymal stem cell research
- Tissue Engineering and Regenerative Medicine
- Chronic Kidney Disease and Diabetes
- Pluripotent Stem Cells Research
- Stress Responses and Cortisol
- Neuroendocrine regulation and behavior
- Acute Kidney Injury Research
- Renal cell carcinoma treatment
- Organ Donation and Transplantation
- Cardiovascular Effects of Exercise
- Intestinal and Peritoneal Adhesions
- Organ and Tissue Transplantation Research
- Neurogenetic and Muscular Disorders Research
- Connective tissue disorders research
- Health Systems, Economic Evaluations, Quality of Life
- Cardiac Structural Anomalies and Repair
- Metalloenzymes and iron-sulfur proteins
- Pharmacological Effects and Assays
- GDF15 and Related Biomarkers
- Global Financial Regulation and Crises
- Fungal and yeast genetics research
Harvard Stem Cell Institute
2019-2025
Brigham and Women's Hospital
2018-2025
Harvard University
2018-2025
Aetna (United States)
2018
Boston Children's Hospital
2018
Hartford Financial Services (United States)
2018
Biogen (United States)
2010-2018
University of British Columbia
2012-2016
Oregon National Primate Research Center
2006-2009
Oregon Health & Science University
2006-2008
Background Kidney injury is characterized by persisting inflammation and fibrosis, yet mechanisms which inflammatory signals drive fibrogenesis remain poorly defined. Methods RNA sequencing of fibrotic kidneys from patients with CKD identified a metabolic gene signature comprising loss mitochondrial oxidative phosphorylation expression concomitant increase in regulators enzymes glycolysis under the control PGC1 α MYC transcription factors, respectively. We modeled this switch vivo ,...
Acute skeletal muscle injury triggers an expansion of fibro/adipogenic progenitors (FAPs) and a transient stage fibrogenesis characterized by extracellular matrix deposition. While the perpetuation such phase can lead to permanent tissue scarring, consequences its suppression remain be studied. Using model acute damage we were able determine that pharmacological inhibition FAP Nilotinib, tyrosine kinase inhibitor with potent antifibrotic activity, exerts detrimental effect on myogenesis...
Abstract Bioengineering strategies for the fabrication of implantable lymphoid structures mimicking lymph nodes (LNs) and tertiary (TLS) could amplify adaptive immune response therapeutic applications such as cancer immunotherapy. No method to date has resulted in consistent formation high endothelial venules (HEVs), which is specialized vasculature responsible naïve T cell recruitment education both LNs TLS. Here orthogonal induced differentiation human pluripotent stem cells carrying a...
Pathologies characterized by lipomatous infiltration of craniofacial structures as well certain forms lipodystrophies suggest the existence a distinct adipogenic program in cephalic region mammals. Using lineage tracing, we studied origin adipocytes that accumulate both cranial fat depots and during ectopic muscles. We found unlike their counterparts limb muscle, significant percentage is derived from neural crest (NC). In addition, identified population NC-derived...
The suprachiasmatic nucleus plays a key role in the circadian secretion of adrenocortical hormones. However, there is evidence from mouse studies that components clock are also expressed within adrenal gland itself. In present study we performed genome-wide expression profiling to determine whether rhesus monkeys shows temporal gene across 24-h period. We identified 322 transcripts with rhythmic patterns and found phase distribution cycling varied day, more genes showing activation during...
Pericytes are tissue-resident mesenchymal progenitor cells anatomically associated with the vasculature that have been shown to participate in tissue regeneration. Here, we tested hypothesis kidney pericytes, derived from FoxD1+ mesodermal progenitors during embryogenesis, necessary for postnatal homeostasis. Diphtheria toxin delivery FoxD1Cre::RsDTR transgenic mice resulted selective ablation of >90% pericytes but not other cell lineages. Abrupt increases plasma creatinine, blood urea...
Although the immune response within draining lymph nodes (DLNs) has been studied for decades, how their stromal compartment contributes to this process remains be fully explored. Here, we show that donor mast cells were prominent activators of collagen I deposition by fibroblastic reticular (FRCs) in DLNs shortly following transplantation. Serial analysis DLN indicated LN stroma did not return its baseline microarchitecture organ rejection and contained significant fibrosis repetitive...
Cardiovascular disease is the main cause of death and incapacity in Portugal. With population ageing greater survival to initial events, burden incapacity-adjusted life years tends increase, representing a growing challenge for health systems. Patients with cardiovascular travel quickly through healthcare systems, brief interactions, by variety professionals, so critical rethinking care approaches. Integrated has shown be effective patients chronic conditions, associated reduced...
Adult stem cells are activated to proliferate and differentiate during normal tissue homeostasis as well in disease states injury. This activation is a vital component the restoration of function damaged via either complete or partial regeneration. When regeneration does not fully occur, reparative processes involving an overproduction stromal components ensure continuity at expense its structure function, resulting "reparative disorder". from multiple organs have been identified being...
With the increasing volume of cardiovascular surgeries and rising adoption rate new methodologies that serve as a bridge to cardiac transplantation require multiple surgical interventions, formation postoperative intrapericardial adhesions has become challenging problem limits future procedures, causes serious complications, increases medical costs. To prevent this pathology, we developed nanotechnology-based self-healing drug delivery hydrogel barrier composed silicate nanodisks...
Abstract The lack of animal models for some human diseases precludes our understanding disease mechanisms and ability to test prospective therapies in vivo. Generation kidney organoids from Tuberous Sclerosis Complex (TSC) patient-derived-hiPSCs allows us recapitulate a rare tumor called angiomyolipoma (AML). Organoids derived TSC2 −/− hiPSCs but not isogenic +/− or +/+ share common transcriptional signature myomelanocytic cell phenotype with AMLs, develop epithelial cysts, replicating two...
In mammals, adrenal medulla chromaffin cells constitute a fundamental component of the sympathetic nervous system outflow, producing most circulating adrenaline. We recently found that rhesus monkey gland expresses several genes in 24-h rhythmic pattern, including TH (the rate-limiting enzyme catecholamine synthesis) and Atf5 (a transcription factor involved apoptosis neural cell differentiation) together with core-clock genes. To examine whether these play role circadian function, we...
In temperate zones, day length changes markedly across the year, and in many mammals these photoperiodic variations are associated with physiological adaptations. However, influence of this environmental variable on human behavior physiology is less clear, potential underlying mechanisms unknown. To address issue, we examined effect changing photoperiods adrenal gland function ovariectomized female rhesus macaques ( Macaca mulatta ), both terms steroid hormone output gene expression. The...
Tuberous sclerosis complex (TSC) is a genetic disorder affecting multiple organ systems observed in approximately 1 10,000 live births.1,2 Patients with TSC have higher risk of developing benign tumors the brain, kidneys, heart, liver, lungs, and skin, variety neuropsychiatric disorders.3 However, due to rarity TSC, its comorbidity landscape has not been fully investigated. To characterize comorbidities systematically, we employed nationwide health insurance claims dataset analyze determined...