A5031786594- Pulmonary Hypertension Research and Treatments
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Heterotopic Ossification and Related Conditions
- Organ Transplantation Techniques and Outcomes
- Liver Disease and Transplantation
- Genetic Neurodegenerative Diseases
- Renal and related cancers
- Parathyroid Disorders and Treatments
- vaccines and immunoinformatics approaches
- Cancer Genomics and Diagnostics
- TGF-β signaling in diseases
- Mitochondrial Function and Pathology
- Bone Metabolism and Diseases
- Fungal and yeast genetics research
Massachusetts Institute of Technology
2022-2025
IIT@MIT
2021-2024
Allen Institute
2021
Koch Institute for Integrative Cancer Research At MIT
2021
Harvard University
2018-2020
Brigham and Women's Hospital
2018-2020
Tufts University
2016
Human genetics, biomarker, and animal studies implicate loss of function in bone morphogenetic protein (BMP) signaling maladaptive transforming growth factor-β (TGFβ) as drivers pulmonary arterial hypertension (PAH). Although sharing common receptors effectors with BMP/TGFβ, the activin differentiation factor (GDF) ligands PAH are less well defined. Increased expression GDF8, GDF11, A was detected lung lesions from humans experimental rodent models (PH). ACTRIIA-Fc, a potent GDF8/11 ligand...
Rationale: BMP9 (bone morphogenetic protein 9) is a circulating endothelial quiescence factor with protective effects in pulmonary arterial hypertension (PAH). Loss-of-function mutations BMP9, its receptors, and downstream effectors have been reported heritable PAH.Objectives: To determine how an acquired deficiency of signaling might contribute to PAH.Methods: Plasma levels antagonist soluble endoglin were measured group 1 PAH, 2 3 (PH), patients severe liver disease without...
Abstract The osteoblast differentiation capacity of skeletal stem cells (SSCs) must be tightly regulated, as inadequate bone formation results in low mass and fragility, over-exuberant osteogenesis heterotopic ossification (HO) soft tissues. RUNX2 is essential for tuning this balance, but the mechanisms posttranslational control remain to fully elucidated. Here, we identify that a CK2/HAUSP pathway key regulator stability, Casein kinase 2 (CK2) phosphorylates RUNX2, recruiting deubiquitinase...
Immune checkpoint blockade (ICB) enhances T cell responses against cancer, leading to long-term survival in a fraction of patients. CD8 + differentiation response chronic antigen stimulation is highly complex, and it remains unclear precisely which states at anatomic sites are critical for the ICB. We identified an intermediate-exhausted population white pulp spleen that underwent substantial expansion ICB gave rise tumor-infiltrating clonotypes. Increased systemic redirected this toward...
<h3>Background</h3> CD8<sup>+</sup> T cell fate decision refers to the differentiation of a naïve into effector, memory, exhausted, or other fates. Evidence from chronic infection and cancer models suggest that signals during priming are especially important in determining thus functional quality response.<sup>1–4</sup> Priming interactions highly complex, requiring integration multiple signals, each which varies strength duration. Thus, we currently do not comprehend combinatorial...
<h3>Background</h3> Immune checkpoint blockade (ICB) provides durable clinical and survival benefits for a fraction of cancer patients.<sup>1–3</sup> ICB blocks interactions between inhibitory receptors expressed by exhausted CD8<sup>+</sup> T cells their ligands tumor or antigen-presenting cells, enhancing the functionality clonal expansion thereby improving overall anti-tumor immune response.<sup>4</sup> Recent studies have underscored remarkable heterogeneity within cell exhaustion...
<h3>Background</h3> Conventional dendritic cells (cDC) are critical mediators of protective anti-tumor CD8<sup>+</sup> T-cell responses.<sup>1</sup> Batf3-driven DC1 the predominant cDC subset driving immunity due to their specialized ability cross-present antigens for activation.<sup>2–4</sup> However, contribution other tumor-infiltrating DC subsets such as CD11b<sup>+</sup> DC2 remains poorly characterized. Recent studies suggest that under inflammation, can exist in various functional...
<h3>Background</h3> Fate decision in CD8<sup>+</sup> T cells refers to the differentiation that occurs when a naïve cell enters into effector, memory, exhausted, or other states. Multiple models of fate have been proposed, but exact determinants are unknown. Evidence from chronic infection and cancer support notion signals during priming especially important determining both functional quality response. Priming interactions highly complex, requiring integration multiple signals, each which...
Introduction: Therapies targeting the underlying mechanisms of pulmonary arterial hypertension (PAH) might modify natural history disease. The genetics heritable PAH implicate deficient BMP signaling as a pathogenetic driver. Lung tissues from experimental and human exhibit & excessive TGFβ signaling. While previous studies suggest agonism BMP9 or inhibition may prevent PH, roles activin growth differentiation factor (GDF) ligand are unclear. ACTRIIA-Fc (sotatercept) is an activin-...
<h3>Background</h3> Fate decision in CD8<sup>+</sup> T cells refers to the process of differentiation that occurs when a naïve cell enters into effector, memory, exhausted, or other states. Multiple models fate have been proposed, but exact determinants are unknown. Evidence LCMV and cancer support notion signals during priming especially important deciding decisions made early process. Priming interactions highly complex, requiring integration multiple signals. Each these can vary strength...