A5049631164- Prostate Cancer Treatment and Research
- Muscle Physiology and Disorders
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Cancer Cells and Metastasis
- Cardiomyopathy and Myosin Studies
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Cancer-related gene regulation
- Estrogen and related hormone effects
- Calpain Protease Function and Regulation
- Cancer-related molecular mechanisms research
- Radiopharmaceutical Chemistry and Applications
- Phagocytosis and Immune Regulation
- Sirtuins and Resveratrol in Medicine
- Cardiovascular Effects of Exercise
- RNA modifications and cancer
- Apelin-related biomedical research
- Cancer, Stress, Anesthesia, and Immune Response
- Mechanisms of cancer metastasis
- Mitochondrial Function and Pathology
- Radiomics and Machine Learning in Medical Imaging
- Chemical Reactions and Isotopes
- Protein Degradation and Inhibitors
- Protein Tyrosine Phosphatases
Roswell Park Comprehensive Cancer Center
2016-2024
Institute of Neurobiology
2020
Cancer Genetics (United States)
2016-2018
University of Rochester
2014-2018
University of North Carolina at Chapel Hill
2011-2016
Drug resistance in cancer is often linked to changes tumor cell state or lineage, but the molecular mechanisms driving this plasticity remain unclear. Using murine organoid and genetically engineered mouse models, we investigated causes of lineage prostate its relationship antiandrogen resistance. We found that initiates an epithelial population defined by mixed luminal-basal phenotype it depends on increased Janus kinase (JAK) fibroblast growth factor receptor (FGFR) activity. Organoid...
Abstract Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive cancer, defined by the progression localized disease to metastasis, is responsible for majority of cancer–associated mortality. Recent gene expression profiling has proven successful in predicting outcome cancer patients; however, they have yet provide targeted therapy approaches that could inhibit a patient's metastatic disease. Experimental Design: We interrogated total seven...
FOXA1 is a nonhistone substrate of EZH2, promoting cell growth and sensitizing some prostate cancer to enzymatic EZH2 inhibitors.
Notch signaling can have either an oncogenic or tumor-suppressive function in cancer depending on the type and cellular context. While be early prostate cancer, we identified significant downregulation of pathway during progression from adenocarcinoma to neuroendocrine (NE) where it functions as a tumor suppressor. Activation NE Rb1/Trp53-deficient models led phenotypic conversion toward more indolent, non-NE state with glandular features expression luminal lineage markers. This was...
Targeting cell surface molecules using radioligand and antibody-based therapies has yielded considerable success across cancers. However, it remains unclear how the expression of putative lineage markers, particularly molecules, varies in process plasticity, wherein tumor cells alter their identity acquire new oncogenic properties. A notable example plasticity is transformation prostate adenocarcinoma (PRAD) to neuroendocrine cancer (NEPC)—a growing resistance mechanism that results loss...
Aims Muscle ring finger (MuRF) proteins have been implicated in the transmission of mechanical forces to nuclear cell signaling pathways through their association with sarcomere. We recently reported that MuRF1, but not MuRF2, regulates pathologic cardiac hypertrophy vivo . This was surprising given MuRF1 and MuRF2 interact each other many same sarcomeric experimentally. Methods Results Mice missing all four alleles [MuRF1/MuRF2 double null (DN)] were born a massive spontaneous hypertrophic...
The carboxyl terminus of Hsp70‐interacting protein (CHIP) is a ubiquitin ligase/cochaperone critical for the maintenance cardiac function. Mice lacking CHIP (CHIP−/−) suffer decreased survival, enhanced myocardial injury and increased arrhythmias compared with wild‐type controls following challenge ischaemia reperfusion injury. Recent evidence implicates role in chaperone‐assisted selective autophagy, process that associated exercise‐induced cardioprotection. To determine whether involved we...
Background Prostate cancer (PCa) is diagnosed at the highest rate of all non‐cutaneous male cancers in United States. The androgen‐dependent (AD) transcription factor, androgen receptor (AR), drives PCa—but inhibiting AR or biosynthesis induces remission for only a short time. At which point, patients acquire more aggressive castration‐resistant (CR) disease with re‐activated AR‐dependent signaling. To combat treatment resistance, down‐regulating protein expression has been considered as...
Recent studies implicate the muscle-specific ubiquitin ligase muscle RING finger-1 (MuRF1) in inhibiting pathological cardiomyocyte growth vivo by transcription factor SRF. These led us to hypothesize that MuRF1 similarly inhibits insulin-like factor-I (IGF-I)-mediated physiological growth. We identified two lines of evidence support this hypothesis: IGF-I stimulation cardiac-derived cells with knockdown 1) exhibited an exaggerated hypertrophy and, 2) conversely, increased...
Thyroid hormone (TH) is recognized for its role in cellular metabolism and growth participates homeostasis of the heart. T3 activates pro-survival pathways including Akt mTOR. Treatment with after myocardial infarction cardioprotective promotes elements physiological hypertrophic response cardiac injury. Although known to benefit heart, very little about regulation at molecular level has been described date. The ubiquitin proteasome system (UPS) regulates nuclear receptors such as estrogen,...
Survival of immune and nonimmune cells relies on Axl, a receptor tyrosine kinase, which is implicated in hypertension. Activated T lymphocytes are involved regulation high blood pressure. The goal the study was to investigate role Axl T-lymphocyte functions its contribution salt-dependent hypertension.We report increased apoptosis peripheral from Axl(-/-) mice because lower numbers white mostly lymphocytes. In vitro studies showed modest reduction interferon gamma production type 1 helper...
Targeting cell surface molecules using radioligand and antibody-based therapies has yielded considerable success across cancers. However, it remains unclear how the expression of putative lineage markers, particularly molecules, varies in process plasticity, wherein tumor cells alter their identity acquire new oncogenic properties. A notable example plasticity is transformation prostate adenocarcinoma (PRAD) to neuroendocrine cancer (NEPC)--a growing resistance mechanism that results loss...
Abstract Introduction: Previous studies have tested the hypothesis that calpain and/or proteasome inhibition is beneficial in Duchenne muscular dystrophy, based largely on evidence and activities are enhanced mdx mouse. Methods: mRNA expression of ubiquitin‐proteasome system components were determined using real‐time polymerase chain reaction skeletal muscle heart golden retriever dystrophy model. Similarly, 1 2 fluorometric activity assays. Results: We found less than half muscles had...
Prostate cancer variants expressing alternative lineage markers appear at relapse from antiandrogen therapy. We show that loss of the retinoblastoma (RB1) and tumor protein 53 (TP53) genes drives expression stem cell reprogramming factors, plasticity, resistance. Epigenetic manipulation restores sensitivity—suggesting an approach for treating lethal prostate cancers.
Abstract Lineage plasticity is a well–established mechanism of resistance to targeted therapies in lung and prostate cancer, where tumors transition from adenocarcinoma small–cell or neuroendocrine carcinoma. Through single–cell analysis cohort heavily–treated castration–resistant human cancers (CRPC), we report greater degree than previously appreciated, with multiple distinct (NEPC), mesenchymal (EMT–like), other subpopulations detected within single biopsies. To explore the steps leading...
Chemoprevention trials for prostate cancer by androgen receptor or synthesis inhibition have proven ineffective. Recently, it has been demonstrated that the histone methlytransferase, EZH2 is deregulated in mouse and human high-grade prostatic intraepithelial neoplasia (HG-PIN). Using preclinical models of cancer, we demonstrate genetic chemical disruption expression catalytic activity reversed HG-PIN phenotype. Furthermore, function was associated with loss cellular proliferation induction...