A5014609535- Estrogen and related hormone effects
- Cancer, Lipids, and Metabolism
- Cholesterol and Lipid Metabolism
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Impact on Reproduction
- Hormonal Regulation and Hypertension
- Inflammatory mediators and NSAID effects
- FOXO transcription factor regulation
- Reproductive biology and impacts on aquatic species
- Endoplasmic Reticulum Stress and Disease
- Immune cells in cancer
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Ferroptosis and cancer prognosis
- Drug Transport and Resistance Mechanisms
- Immune Cell Function and Interaction
- HER2/EGFR in Cancer Research
- Extracellular vesicles in disease
- Ion Channels and Receptors
- Prostate Cancer Treatment and Research
- Cancer, Hypoxia, and Metabolism
- Computational Drug Discovery Methods
- Calcium signaling and nucleotide metabolism
- Adipose Tissue and Metabolism
- Effects and risks of endocrine disrupting chemicals
- Cancer Immunotherapy and Biomarkers
University of Illinois Urbana-Champaign
2016-2025
Urbana University
2020-2025
McMaster University
2024
Illinois College
2023
University of Illinois Chicago
2016-2022
University of Illinois System
2016-2018
Duke University
2009-2017
University of Calgary
2006-2016
Duke Medical Center
2009-2016
Duke University Hospital
2009-2016
Cholesterol and Cancer Obesity high cholesterol levels are associated with an increased risk of breast cancer in post-menopausal women. Nelson et al. (p. 1094 ) found that a specific metabolite cholesterol, 27-hydroxycholesterol (27HC), promoted tumor growth metastasis mouse models mammary by serving as partial agonist for the estrogen receptor liver X receptor. The most aggressive human cancers were to express highest level enzyme converts 27HC, suggesting 27HC produced within tumors (in...
Flow cytometry is used extensively to examine immune cells in non-lymphoid tissues. However, a method of flow cytometric analysis that both comprehensive and widely applicable has not been described. We developed protocol for the tissues, including methods tissue preparation, 10-fluorochrome panel cell staining, standardized gating strategy, allows simultaneous identification quantification all major types variety normal inflamed demonstrate our basic minimizes loss, reliably distinguishes...
Obesity and elevated circulating cholesterol are risk factors for breast cancer recurrence, while the use of statins, biosynthesis inhibitors widely used treating hypercholesterolemia, is associated with improved disease-free survival. Here, we show that mediates metastatic effects a high-fat diet via its oxysterol metabolite, 27-hydroxycholesterol. Ablation or inhibition CYP27A1, enzyme responsible rate-limiting step in 27-hydroxycholesterol biosynthesis, significantly reduces metastasis...
Stimulation of resting CD4 + T lymphocytes leads to rapid proliferation and differentiation into effector (Teff) or inducible regulatory (Treg) subsets with specific functions promote suppress immunity. Importantly, Teff Treg use distinct metabolic programs support subset specification, survival, function. Here, we describe that the orphan nuclear receptor estrogen-related receptor-α (ERRα) regulates pathways critical for Teff. Resting cells expressed low levels ERRα protein increased on...
Previously published reports indicate that serum copper levels are elevated in patients with prostate cancer and increased uptake can be used as a means to image tumors. It is unclear, however, what extent required for cell function we observed only modest effects of chelation strategies on the growth these cells vitro. With goal exploiting proclivity uptake, developed "conditional lethal" screen identify compounds whose cytotoxic actions were manifested copper-dependent manner. Emerging...
The purpose of this study is to investigate the effects exercise on cancer progression, metastasis, and underlying mechanisms in an orthotopic model murine prostate cancer. C57BL/6 male mice (6–8 wk age) were orthotopically injected with transgenic adenocarcinoma mouse C-1 cells (5 × 10 5 ) randomly assigned ( n = 28) or a non-intervention control 31) groups. group was given voluntary access wheel 24 h/day for duration study. Four per serially killed days 14, 31, 36; remaining 38 (exercise,...
There is compelling evidence to suggest that drugs function as pure estrogen receptor (ER-α) antagonists, or downregulate the expression of ER-α, would have clinical use in treatment advanced tamoxifen- and aromatase-resistant breast cancer. Although such compounds are currently development, we reasoned, based on our understanding ER-α pharmacology, there may already exist among most recently developed selective modulators (SERM) usage cancer therapeutics. Thus, objective was identify...
Obesity and altered lipid metabolism are risk factors for breast cancer in pre- post-menopausal women. These pathologic relationships have been attributed part to the impact of cholesterol on biophysical properties cell membranes influence these changes signaling events initiated at membrane. However, more recent studies indicated that oxysterol 27-hydroxycholesterol (27HC), not per se, may be primary biochemical link between cancer. The enzyme responsible production 27HC from cholesterol,...
Abstract In this study, we used a bioinformatic approach to identify genes whose expression is dysregulated in human prostate cancers. One of the most dramatically downregulated identified encodes CYP27A1, an enzyme involved regulating cellular cholesterol homeostasis. Importantly, lower CYP27A1 transcript levels were associated with shorter disease-free survival and higher tumor grade. Loss cancer was confirmed at protein level by immunostaining for annotated tissue microarrays. Restoration...
Endocrine therapy, using tamoxifen or an aromatase inhibitor, remains a first-line treatment for estrogen receptor 1 (ESR1) positive breast cancer. However, tumor resistance limits the duration of response. The clinical efficacy fulvestrant, selective ER degrader (SERD) that triggers degradation, has confirmed ESR1 often engaged in endocrine therapy resistant cancers. Recently developed, modulators (SERMs)/SERD hybrids (SSHs) facilitate degradation cancer cells and reproductive tissues have...
Abstract Tumor-associated myeloid cells regulate tumor growth and metastasis, their accumulation is a negative prognostic factor for breast cancer. Here we find calcium/calmodulin-dependent kinase (CaMKK2) to be highly expressed within intratumoral in mouse models of cancer, demonstrate that its inhibition suppresses by increasing effector CD8 + T immune-stimulatory subsets. macrophages (TAMs) isolated from Camkk2 −/− mice higher levels chemokines involved the recruitment compared WT....
Obesity leads to an increased risk for type 2 diabetes, heart disease, stroke, and cancer. The causal link between obesity these pathologies has recently been identified as chronic low-grade systemic inflammation initiated by pro-inflammatory macrophages in visceral adipose tissue. Current medications based on small-molecule drugs yield significant off-target side effects with long-term use, therefore there is a major need targeted therapies. Here we report that nanoscale polysaccharides...
While stimulator of interferon genes (STING) activation in innate immune cells the tumor microenvironment can result CD8 T cell-dependent antitumor immunity, whether STING signaling affects CD4 T-cell responses remains elusive.Here, we tested modulated effector functions vivo by analyzing tumor-infiltrating and evaluating contribution cell-derived cytokines activity ligand 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) two mouse models. We performed ex experiments to...
Abstract As key mediators of cellular communication, extracellular vesicles (EVs) have been actively explored for diagnostic and therapeutic applications. However, effective methods to functionalize EVs modulate the interaction between recipient cells are still lacking. Here we report a facile universal metabolic tagging technology that can install unique chemical tags (e.g., azido groups) onto EVs. The surface enable conjugation molecules via efficient click chemistry, tracking targeted...
Estrogens work by binding to and activating specific estrogen receptors (ERs). Although mammals have two major nuclear ER subtypes (ERα ERβ), three been shown in teleost fish (ERα, ERβ-I, ERβ-II). 17β-Estradiol stimulates the production of an egg yolk precursor protein (vitellogenin) liver oviparous species, including goldfish. However, functional involvement this process is not fully understood. Here, using primary goldfish hepatocytes, we test hypothesis that all are functionally involved...
Osteoporosis and age-related bone loss are important public health concerns. Therefore, there is a high level of interest in the development medical interventions lifestyle changes that reduce incidence osteoporosis loss. Decreased mineral density associated with cholesterol, patients on statins have increased densities, strongly implicating cholesterol as negative regulator homeostasis. In this study, using both molecular pharmacological approaches, we been able to demonstrate primary...
Osteoporosis is an important clinical problem, affecting more than 50% of people over age 50 yr. Estrogen signaling critical for maintaining proper bone density, and the identification endogenous selective estrogen receptor (ER) modulator, 27-hydroxycholesterol (27HC), suggests a mechanism by which nutritional/metabolic status can influence biology. With its levels directly correlated with cholesterol, new possibility emerges wherein 27HC links cholesterol to homeostasis. In these studies,...