A5003257047- Tuberous Sclerosis Complex Research
- Eosinophilic Disorders and Syndromes
- Pulmonary Hypertension Research and Treatments
- Vascular Tumors and Angiosarcomas
- Histiocytic Disorders and Treatments
- Microtubule and mitosis dynamics
- Renal and related cancers
- Medical Imaging and Pathology Studies
- Asthma and respiratory diseases
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- MXene and MAX Phase Materials
- Mass Spectrometry Techniques and Applications
- Genetic and Kidney Cyst Diseases
- Statistical Methods in Clinical Trials
- Kruppel-like factors research
- Transplantation: Methods and Outcomes
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Systems, Economic Evaluations, Quality of Life
- Eicosanoids and Hypertension Pharmacology
- Renal cell carcinoma treatment
- Neuroscience and Neuropharmacology Research
- PI3K/AKT/mTOR signaling in cancer
- Cell Adhesion Molecules Research
- Blood disorders and treatments
- Polyomavirus and related diseases
University of Pennsylvania
2015-2024
Hospital of the University of Pennsylvania
2024
Philadelphia University
2023
Pulmonary Associates
2021
Penn Center for AIDS Research
2018
Abstract Lymphangioleiomyomatosis (LAM) is a rare fatal cystic lung disease due to bi-allelic inactivating mutations in tuberous sclerosis complex (TSC1/TSC2) genes coding for suppressors of the mechanistic target rapamycin 1 (mTORC1). The origin LAM cells still unknown. Here, we profile compared an age- and sex-matched healthy control as hypothesis-generating approach identify cell subtypes that are specific LAM. Our single-cell RNA sequencing (scRNA-seq) analysis reveals novel mesenchymal...
Pulmonary lymphangioleiomyomatosis (LAM) is a slow-progressing metastatic disease that driven by mutations in the tumor suppressor tuberous sclerosis complex 1/2 (TSC1/2). Rapamycin inhibits LAM cell proliferation and only approved treatment, but it cannot cause regression of existing lesions can stabilize disease. However, other cancers, immunotherapies such as checkpoint blockade against PD-1 its ligand PD-L1 have shown promise causing even curing some patients. Thus, we asked whether has...
Pulmonary lymphangioleiomyomatosis (LAM), a rare progressive lung disease associated with mutations of the tuberous sclerosis complex 2 ( Tsc2) tumor suppressor gene, manifests by neoplastic growth LAM cells, induction cystic destruction, and respiratory failure. severity correlates upregulation in serum prolymphangiogenic vascular endothelial factor D (VEGF-D) that distinguishes from other diseases. The goals our study was to determine whether Tsc2 deficiency upregulates VEGF-D, axitinib,...
N-methyl-D-aspartate (NMDA) receptors are widely expressed in the central nervous system. However, their presence and function at extraneuronal sites is less well characterized. In present study, we examined expression of NMDA receptor subunit mRNA protein human pulmonary artery (HPA) by quantitative polymerase chain reaction (PCR), immunohistochemistry immunoblotting. We demonstrate that both GluN1 GluN2 mRNAs HPA. addition, (A-D) proteins smooth muscle cells (HPASMCs) vitro vivo. These...
Lymphangioleiomyomatosis (LAM) is a rare and progressive systemic disease affecting mainly young women of childbearing age. A deterioration in lung function driven by neoplastic growth atypical smooth muscle-like LAM cells the pulmonary interstitial space that leads to cystic destruction spontaneous pneumothoraces. Therapeutic options for preventing progression are limited often end with transplantation temporarily delaying an inevitable decline. To identify new therapeutic strategies this...
Lymphangioleiomyomatosis (LAM) is a rare genetic lung disease. Unfortunately, treatment with the mTORC1 inhibitor Rapamycin only slows disease progression, and incomplete responses are common. Thus, there remains an urgent need to identify new targets for development of curative LAM treatments. Nitazoxanide (NTZ) orally bioavailable antiprotozoal small molecule drug approved diarrhea caused by
Abstract Lymphangioleiomyomatosis is a rare destructive lung disease affecting primarily women and the primary manifestation of tuberous sclerosis complex (TSC). In lymphangioleiomyomatosis, biallelic loss TSC1/2 leads to hyperactivation mTORC1 inhibition autophagy. To determine how metabolic vulnerabilities TSC2-deficient cells can be targeted, we performed high-throughput screen utilizing “Repurposing” library at Broad Institute MIT Harvard (Cambridge, MA), with or without autophagy...
Lymphangioleiomyomatosis (LAM) is a rare, almost exclusively female lung disease linked to inactivating mutations in tuberous sclerosis complex 2 (TSC2), tumor suppressor gene that controls cell metabolic state and growth via regulation of the mechanistic target rapamycin (mTORC1) signaling. mTORC1 frequently activated human cancers and, although inhibitor has cytostatic effect, it is, general, unable elicit robust curative effect or regression. Using RNA-Seq, we identified (1) Insulin-like...
Lymphangioleiomyomatosis (LAM) is a progressive cystic lung disease caused by tuberous sclerosis complex 1/2 (TSC1/2) gene mutations in pulmonary mesenchymal cells resulting activation of the mechanistic target rapamycin 1 (mTORC1). A subset LAM patients develops vascular remodeling and hypertension. Little, however, known regarding how communicate with endothelial (ECs) to trigger remodeling. In end-stage explants, we identified cell dysfunction characterized increased proliferation,...
Lymphangioleiomyomatosis (LAM) is a rare metastatic cystic lung disease due to mutation in TSC tumor suppressor, resulting hyperactive mTOR growth pathways. Sirolimus (rapamycin), an allosteric mTORC1 inhibitor, therapeutic option for women with LAM but it only maintains volume during treatment and does not provide benefit all patients. The two major protein synthesis pathways are via S6K/S6 or 4E-BP/eIF4E activation. We aimed investigate rapamycin combination compounds that target...
Recurrent infections are a hallmark of STAT3 dominant-negative hyper-IgE syndrome (STAT3 HIES), rare immunodeficiency previously known as Jobs syndrome, along with elevated IgE levels and impaired neutrophil function. We have been developing nanoparticles trophism that home to the sites infection via these first-responder leukocytes, named neutrophil-avid nanocarriers (NANs). Here, we demonstrate human neutrophils can phagocytose nanogels (NGs), type NAN, enhanced uptake after particle serum...
Mutations in the Tuberous Sclerosis Complex (TSC) genes result hyperactivation of mechanistic/mammalian target rapamycin 1 (mTORC1) growth pathway mesenchymal pulmonary cells. Rapamycin (Sirolimus
LAM is rare genetic lung disease caused by the inactivating mutations in TSC1/2 genes, resulting mTORC1hyperactivation, abnormal cell growth causing cystic destruction requiring transplantation. We identified expression of pro-fibrotic <i>ACTA2, COL1A1, COL1A2, COL6A1, COL3A1</i>, and <i>TGFB3</i> transcripts PDGFRa+ fibroblasts from demonstrating their activation, upregulation transitional AT2/AT1 state, a hallmark injury/repair. To study molecular mechanisms involved fibroblast...
<div>Abstract<p>Lymphangioleiomyomatosis is a rare destructive lung disease affecting primarily women and the primary manifestation of tuberous sclerosis complex (TSC). In lymphangioleiomyomatosis, biallelic loss TSC1/2 leads to hyperactivation mTORC1 inhibition autophagy. To determine how metabolic vulnerabilities TSC2-deficient cells can be targeted, we performed high-throughput screen utilizing “Repurposing” library at Broad Institute MIT Harvard (Cambridge, MA), with or...
<div>Abstract<p>Lymphangioleiomyomatosis is a rare destructive lung disease affecting primarily women and the primary manifestation of tuberous sclerosis complex (TSC). In lymphangioleiomyomatosis, biallelic loss TSC1/2 leads to hyperactivation mTORC1 inhibition autophagy. To determine how metabolic vulnerabilities TSC2-deficient cells can be targeted, we performed high-throughput screen utilizing “Repurposing” library at Broad Institute MIT Harvard (Cambridge, MA), with or...
<p>Ritanserin inhibits macropinocytosis and acidic organelle homeostasis in TSC2-deficient cells</p>
<p>Purine metabolism following ritanserin treatment in Tsc2-deficient cells</p>
<p>Lipidomic analysis of ritanserin treated Tsc2-deficient cells</p>
<p>Ritanserin inhibits macropinocytosis and acidic organelle homeostasis in TSC2-deficient cells</p>
<p>Gene expression of DGKs and pentose phosphate pathway genes.</p>
<p>Purine metabolism following ritanserin treatment in Tsc2-deficient cells</p>
<p>Ritanserin inhibits the proliferation of multiple TSC2-deficient cell lines, independently autophagy.</p>