A5083024509- Cancer Cells and Metastasis
- Polyamine Metabolism and Applications
- Epigenetics and DNA Methylation
- Amino Acid Enzymes and Metabolism
- Immune cells in cancer
- Cannabis and Cannabinoid Research
- Cancer Genomics and Diagnostics
- Pancreatic function and diabetes
- Immune Cell Function and Interaction
- Phagocytosis and Immune Regulation
- Genomics and Chromatin Dynamics
- Intraperitoneal and Appendiceal Malignancies
- Cellular Mechanics and Interactions
- Cancer-related Molecular Pathways
- Biomedical Research and Pathophysiology
- Appendicitis Diagnosis and Management
- Fungal Biology and Applications
- Polyomavirus and related diseases
- Reproductive System and Pregnancy
- Mast cells and histamine
- Genetics and Neurodevelopmental Disorders
- RNA and protein synthesis mechanisms
- Porphyrin Metabolism and Disorders
- Fibroblast Growth Factor Research
- Endoplasmic Reticulum Stress and Disease
Johns Hopkins University
2017-2024
Johns Hopkins Medicine
2018-2024
University of Baltimore
2019-2021
Sidney Kimmel Comprehensive Cancer Center
2017-2021
University of Nebraska Medical Center
2021
University of Nebraska at Kearney
2021
Gettysburg College
2016
Triple-negative breast cancer (TNBC) is an aggressive subtype associated with early metastatic recurrence and worse patient outcomes. TNBC tumors express molecular markers of the epithelial-mesenchymal transition (EMT), but its requirement during spontaneous metastasis in vivo remains incompletely understood. We demonstrated that from a genetically engineered mouse model (GEMM), multiple patient-derived xenografts, archival samples exhibited large populations hybrid E/M cells lead invasion...
Natural killer (NK) cells have potent antitumor and antimetastatic activity. It is incompletely understood how cancer escape NK cell surveillance. Using ex vivo in models of metastasis, we establish that keratin-14+ breast are vulnerable to cells. We then discovered exposure causes lose their cytotoxic ability promote metastatic outgrowth. Gene expression comparisons revealed healthy an active molecular phenotype, whereas tumor-exposed (teNK) resemble resting Receptor–ligand analysis between...
Although ovarian cancer has a low incidence rate, it remains the most deadly gynecologic malignancy. Previous work demonstrated that DNMTi 5-Azacytidine (5AZA-C) activates type I interferon signaling to increase IFNγ+ T cells and natural killer (NK) reduce percentage of macrophages in tumor microenvironment. To improve efficacy epigenetic therapy, we hypothesized addition α-difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor, may further decrease immunosuppressive cell...
Although chemotherapies kill most cancer cells, stem cell-enriched survivors seed metastasis, particularly in triple-negative breast cancers (TNBC). TNBCs arise from and are enriched for tumor cells. Here, we tested if inhibition of DOT1L, an epigenetic regulator normal tissue stem/progenitor populations, would target TNBC cells.Effects DOT1L by EPZ-5676 on cell properties were three lines four patient-derived xenograft (PDX) models isolated (CSC)-enriched ALDH1+ ALDH1- populations. RNA...
Polyamines are small polycationic alkylamines involved in many fundamental cellular processes, including proliferation, nucleic acid synthesis, apoptosis, and protection from oxidative damage. It has been proposed that addition to these functions, elevated levels of polyamines promote longevity various biological systems, yeast, Drosophila, murine models. A series vitro mechanistic studies by multiple investigators led the conclusion exogenous spermidine promotes through autophagy induction;...
Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes biosynthesis polyamine from its precursor spermidine, deficiency causes lack with an accumulation spermidine. polyamines, spermine, spermidine play essential cellular roles that require tight homeostatic control to ensure...
Cisplatin-induced nephrotoxicity limits its use in many cancer patients. The expression of enzymes involved polyamine catabolism, spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMOX) increase the kidneys mice treated with cisplatin. We hypothesized that enhanced catabolism contributes to tissue damage cisplatin acute kidney injury (AKI). Using gene knockout chemical inhibitors, role AKI was examined. Deficiency SSAT, SMOX or neutralization toxic products degradation,...
Curcumin, a natural polyphenol that contributes to the flavor and yellow pigment of spice turmeric, is known for its antioxidant, anti-inflammatory, anticarcinogenic properties. Capable affecting initiation, promotion, progression carcinogenesis through multiple mechanisms, curcumin has potential utility both chemoprevention chemotherapy. Previous studies demonstrated can inhibit ornithine decarboxylase (ODC) activity in human leukemia breast cancer cells, pretreatment with dietary blocks...
Dual inhibitors of LSD1 and SMOX, with no activity against <italic>N</italic><sup>1</sup>-acetylpolyamine oxidase (PAOX).
Therapeutic interventions are designed to perturb the function of a biological system. However, there many types proteins that cannot be targeted with conventional small molecule drugs. Accordingly, identified gene-regulatory drivers and downstream effectors currently undruggable. Drivers often connected by druggable signaling regulatory intermediates. Methods identify intermediates therefore have general value in expanding set targets available for hypothesis-driven validation. Here we...
Tuberous sclerosis complex (TSC) is an autosomal dominant neurodevelopmental disorder and the quintessential of mechanistic Target Rapamycin Complex 1 (mTORC1) dysregulation. Loss either causative gene, TSC1 or TSC2, leads to constitutive mTORC1 kinase activation a pathologically anabolic state macromolecular biosynthesis. Little known about organ-specific metabolic reprogramming that occurs in TSC-affected organs. Using mouse model TSC which Tsc2 disrupted radial glial precursors their...
Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes biosynthesis polyamine from its precursor spermidine, deficiency causes lack with an accumulation spermidine. polyamines, spermidine play essential cellular roles that require tight homeostatic control to ensure normal cell...
Abstract Background Polyamine catabolism plays a key role in maintaining intracellular polyamine pools, yet its physiological significance is largely unexplored. Here, we report that the disruption of leads to severe cerebellar damage and ataxia, demonstrating fundamental maintenance function integrity. Methods Mice with simultaneous deletion two principal catabolic enzymes, spermine oxidase spermidine/spermine N 1 -acetyltransferase ( Smox / Sat1 -dKO), were generated by crossbreeding -KO −...
The Zika virus (ZIKV) is primarily transmitted via an infected mosquito bite, during sexual intercourse, or in utero mother to child transmission. When a fetus infected, both neurological malformations and deficits brain development are frequently manifested. As such, there need for vaccines drugs that may be used cure ZIKV infections. Metabolic pathways play crucial role cell differentiation development. More importantly, polyamines key replication translation of several RNA viruses,...
The polyamines putrescine, spermidine, and spermine are required for normal eukaryotic cellular functions. However, the minimum requirement varies widely, ranging from very high concentrations (mm) in mammalian cells to extremely low yeast Saccharomyces cerevisiae Yeast strains deficient polyamine biosynthesis (spe1Δ, lacking ornithine decarboxylase, spe2Δ, SAM decarboxylase) require externally supplied polyamines, but supplementation with as little 10-8 m spermidine restores their growth....
Supplementary Figure from DOT1L Is a Novel Cancer Stem Cell Target for Triple-Negative Breast
Abstract Several cancer subtypes (pancreatic, breast, liver, and colorectal) rapidly advance to higher aggressive stages in diabetes. Though hyperglycemia has been considered as a fuel for growth of cells, pathways leading this condition are still under investigation. Cellular polyamines can modulate normal cell growth, inhibitors polyamine synthesis have approved treating colon cancer, however the role diabetes-mediated advancement is unclear yet. We hypothesized that metabolic pathway...
Abstract Although ovarian cancer has a low incidence rate encompassing roughly 1% of all new cancers, it remains the most deadly gynecologic malignancy. Our lab designed novel combination therapy which combines DNA methyl transferase inhibitor (DNMTi) and ornithine decarboxylase that together, alter tumor microenvironment to inhibit growth. Previous work demonstrated DNMTi 5-Azacytidine (AZA) activates type I interferon signaling (Li, 2014, Chiappinelli, 2015) increase IFNγ+ T cells NK...