A5085589424- Pancreatic and Hepatic Oncology Research
- Melanoma and MAPK Pathways
- Immunotherapy and Immune Responses
- Cutaneous Melanoma Detection and Management
- Cancer, Lipids, and Metabolism
- Skin Protection and Aging
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- Signaling Pathways in Disease
- Protein Degradation and Inhibitors
- Peroxisome Proliferator-Activated Receptors
- Angiogenesis and VEGF in Cancer
- Epigenetics and DNA Methylation
- Wnt/β-catenin signaling in development and cancer
- RNA Interference and Gene Delivery
- Heat shock proteins research
- melanin and skin pigmentation
- Immune cells in cancer
- Parathyroid Disorders and Treatments
- Eicosanoids and Hypertension Pharmacology
- Monoclonal and Polyclonal Antibodies Research
- Cell Adhesion Molecules Research
Johns Hopkins University
2001-2025
Sidney Kimmel Cancer Center
2019-2025
Johns Hopkins Medicine
2019-2025
University of Baltimore
2020-2025
Bloomberg (United States)
2023-2025
Sidney Kimmel Comprehensive Cancer Center
2013-2024
Albert Einstein College of Medicine
2023
The Wistar Institute
2013-2023
National Institute on Aging
2005-2023
History of Science Society
2022
We present the AGEMAP (Atlas of Gene Expression in Mouse Aging Project) gene expression database, which is a resource that catalogs changes as function age mice. The database includes for 8,932 genes 16 tissues age. found great heterogeneity amount transcriptional with different tissues. Some displayed large differences old mice, suggesting these may contribute strongly to organismal decline. Other showed few or no age, indicating strong levels homeostasis throughout life. Based on pattern...
We have shown that Wnt5A increases the motility of melanoma cells. To explore cellular pathways involving Wnt5A, we compared gain-of-function (WNT5A stable transfectants) versus loss-of-function (siRNA knockdown) WNT5A by microarray analysis. Increasing suppressed expression several genes, which were re-expressed after small interference RNA-mediated knockdown WNT5A. Genes affected include KISS-1, a metastasis suppressor, and CD44, involved in tumor cell homing during metastasis. This could...
Abstract Physical changes in skin are among the most visible signs of aging. We found that young dermal fibroblasts secrete high levels extracellular matrix (ECM) constituents, including proteoglycans, glycoproteins, and cartilage-linking proteins. The abundantly secreted was HAPLN1, a hyaluronic proteoglycan link protein. HAPLN1 lost aged fibroblasts, resulting more aligned ECM promoted metastasis melanoma cells. Reconstituting inhibited an microenvironment, 3-D reconstruction models, vivo....
Abstract Purpose: We have shown that the aged microenvironment increases melanoma metastasis, and decreases response to targeted therapy, here we queried anti-PD1. Experimental Design: analyzed relationship between age, anti-PD1, prior therapy in 538 patients. used mouse models of melanoma, analyze intratumoral immune young versus mice confirmed our findings human biopsies. Results: Patients over age 60 responded more efficiently anti-PD-1, likelihood anti-PD-1 increased with even when...
Targeting multiple components of the MAPK pathway can prolong survival patients with BRAFV600E melanoma. This approach is not curative, as some BRAF-mutated melanoma cells are intrinsically resistant to inhibitors (MAPKi). At systemic level, our knowledge how signaling pathways underlie drug resistance needs be further expanded. Here, we have shown that a low basal level mitochondrial biogenesis depend on this process survive MAPKi. Intrinsically exploited an integrated stress response,...
An emerging concept in melanoma biology is that of dynamic, adaptive phenotype switching, where cells switch from a highly proliferative, poorly invasive to invasive, less proliferative one. This may hold significant implications not just for metastasis, but also therapy resistance. We demonstrate switching and subsequent resistance can be guided by changes expression receptors involved the noncanonical Wnt5A signaling pathway, ROR1 ROR2. ROR2 are inversely expressed melanomas negatively...
Significance Despite the promise of personalized cancer medicine, most molecular therapies produce only modest and short-lived patient gains. In addition to drug resistance, it is also possible that tumors adaptively reprogram their signaling pathways evade therapy-induced “stress” and, in process, acquire more aggressive disease traits. We show here small-molecule inhibitors PI3K, a node important therapeutic target, induce transcriptional reprogramming tumors. This involves trafficking...
Significance The mechanical cross talk between intracellular and extracellular forces can promote the invasive potential of tumor cells in tumors. Using a quantitative model, we elucidate two-way feedback loop stress-dependent cell contractility matrix fiber realignment strain stiffening, which enables to polarize enhance their break free from invade into matrix. Our model predicts that intermediate stiffness is optimal for invasion, find positive correlation elongation alignment fibers...
The decline in adaptive immunity, T lymphocyte output, and the contraction of TCR repertoire with age is largely attributable to thymic involution. loss function may be due diminished numbers progenitors critical cytokines hormones from microenvironment. We have previously demonstrated that orexigenic hormone ghrelin expressed by immune cells regulates cell activation inflammation. Here we report receptor expression within thymus progressive aging. Infusion into 14-month-old mice...
Metabolic reprogramming is an important driver of tumor progression; however, the metabolic regulators cell motility and metastasis are not understood. Here, we show that tumors maintain energy production under nutrient deprivation through function HSP90 chaperones compartmentalized in mitochondria. Using cancer lines, found mitochondrial proteins, including necrosis factor receptor–associated protein-1 (TRAP-1), dampen activation nutrient-sensing AMPK its substrate UNC-51–like kinase...