A5078650117- Cancer Cells and Metastasis
- Estrogen and related hormone effects
- Wnt/β-catenin signaling in development and cancer
- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Genomics, phytochemicals, and oxidative stress
- PI3K/AKT/mTOR signaling in cancer
- Cancer Risks and Factors
- Breast Cancer Treatment Studies
- Fibroblast Growth Factor Research
- Neonatal Respiratory Health Research
- Epigenetics and DNA Methylation
- Glutathione Transferases and Polymorphisms
- Lung Cancer Research Studies
- dental development and anomalies
- Xenotransplantation and immune response
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer, Lipids, and Metabolism
- Chemokine receptors and signaling
- Mesenchymal stem cell research
- Bone Metabolism and Diseases
- Cardiovascular Disease and Adiposity
- FOXO transcription factor regulation
- BRCA gene mutations in cancer
- Single-cell and spatial transcriptomics
The University of Texas at Dallas
2023-2024
Indian Institute of Technology Hyderabad
2022
Apollo Hospitals
2022
Princess Margaret Cancer Centre
2013-2019
University Health Network
2013-2015
Ontario Institute for Cancer Research
2010-2014
University of Toronto
2006-2014
Canada Research Chairs
2006
Oxidative stress plays an important role in cancer development and treatment. Recent data implicate the tumor suppressor BRCA1 regulating oxidative stress, but molecular mechanism impact BRCA1-associated tumorigenesis remain unclear. Here, we show that regulates Nrf2-dependent antioxidant signaling by physically interacting with Nrf2 promoting its stability activation. BRCA1-deficient mouse primary mammary epithelial cells low expression of Nrf2-regulated enzymes accumulate reactive oxygen...
Breast cancer is the most common female cancer, affecting approximately one in eight women during their life-time. Besides environmental triggers and hormones, inherited mutations breast 1 (BRCA1) or BRCA2 genes markedly increase risk for development of cancer. Here, using two different mouse models, we show that genetic inactivation key osteoclast differentiation factor RANK mammary epithelium delayed onset, reduced incidence, attenuated progression Brca1;p53 mutation-driven Long-term...
Progesterone-RankL paracrine signaling has been proposed as a driver of stem cell expansion in the mammary gland, and Elf5 is essential for differentiation epithelial progenitor cells. We demonstrate that expression induced by progesterone cooperate to promote alveolar development. The receptor are expressed mutually exclusive pattern, we identify RankL mediator effects on CD61+ cells their consequent differentiation. Blockade action prevented progesterone-induced side branching Elf5(+)...
Systemic and local signals must be integrated by mammary stem progenitor cells to regulate their cyclic growth turnover in the adult gland. Here, we show RANK-positive luminal progenitors exhibiting WNT pathway activation are selectively expanded human breast during progesterone-high menstrual phase. To investigate underlying mechanisms, examined mouse models found that loss of RANK prevents proliferation hormone receptor-negative basal cells, an accompanying activation, and, hence, a...
Abstract The mammary gland experiences substantial remodeling and regeneration during development reproductive life, facilitated by stem cells progenitors that act in concert with physiological stimuli. While studies have focused on deciphering regenerative within the parenchymal epithelium, cell lineages stroma may directly contribute to epithelial biology is unknown. Here we identify, mouse, transition of a PDGFRα + mesenchymal population into progenitors. In addition being adipocyte...
Progesterone drives mammary stem and progenitor cell dynamics through paracrine mechanisms that are currently not well understood. Here, we demonstrate CXCR4, the receptor for stromal-derived factor 1 (SDF-1; CXC12), is a crucial instructor of hormone-induced function. elicits specific changes in transcriptome basal luminal epithelial populations, where CXCL12 CXCR4 represent putative ligand-receptor pair. In situ, localizes to progesterone-receptor-positive cells, whereas induced both...
Liquid biopsies have emerged as convenient alternative diagnostic methods to invasive biopsies, by evaluating disease-specific biomarkers and monitoring the disease risk noninvasively. Phosphatase tensin homolog deleted in chromosome 10 (PTEN) is a potent tumor suppressor, its deletion/mutations are common gliomas.Evaluate feasibility of non-invasive detection PTEN downstream genes serum exosomes glioma patients.PTEN, Yes-associated-protein 1 (YAP1), lysyl oxidase (LOX) transcript expression...
Summary A short duration of breastfeeding is a risk factor for the development high-mortality, postpartum, triple-negative breast cancer. The intrinsic properties cancer-initiating epithelial cells that persist following cessation and mammary gland remodeling are poorly understood. Previously, we showed Platelet-Derived Growth Factor Receptor alpha (PDGFRα)-expressing stromal adipocyte progenitors (MAPs) differentiate into luminal in adult gland. In current study, demonstrate MAP-derived...
Exploring the normal biology and regulation of stem cells has promise to yield insights into etiological roots survival breast cancer cells. Many studies have supported existence a multipotent mammary cell that regenerates all aspects glandular development. However, Van Keymeulen colleagues (2011) illustrated presence lineage-restricted unipotent self-renew collaborate in postnatal development, whereas were found only during embryonic mammogenesis. This prompts re-evaluation currently...
Abstract Treatment challenges in breast cancer arise from significant heterogeneity found within tumors and the surrounding microenvironment. The tumor microenvironment presents a complex ecosystem which comprises diverse stromal cells including immune, endothelial fibroblast cell lineages extracellular matrix that support progression. Adipocytes represent an abundant population normal prior studies have reported crosstalk between adipocytes mammary cells. De-differentiation of into...
Abstract Being overweight or obese is associated with a higher risk of breast cancer (BC) and worse disease-free overall survival compared to normal-weight BC patients. The underlying biological basis for this association attributed alterations in the endocrine inflammatory milieu adipose tissue. However, existing chemotherapy therapy are not effective There critical need pin down tissue cell types that may govern increased adverse outcome obesity. Adipocyte progenitors immature mesenchymal...
Organ development is attributed to stem/progenitor cells which self-renew and differentiate into mature critical for tissue form function. The prostate an epithelial organ that participates in the production of seminal fluid. Bipotent unipotent resident prostatic epithelia are shown support its development. While stroma crucial organogenesis, precise stromal including immature subsets involved biology unknown. Utilizing genetic reporter lineage tracing mouse models, we identify a PDGFRα+...
Abstract Excess fat gain culminating in obesity is a mounting global pandemic associated with myriad of diseases including higher risk developing multiple cancers such as breast cancer. The underlying biological basis for obesity-linked cancer attributed to alterations adipose tissue-derived endocrine, metabolic and inflammatory factors. However, the precise cell types responsible generating cancer-susceptible mammary gland are not well understood. Using diet-induced conjunction genetic...
(Stem Cell Reports 4, 313–322; March 10, 2015)Due to a production error, the title of this paper was incorrectly written as “A Progesterone-CXCR4 Axis Controls Mammary Progenitor Fate in Adult Gland CXCR4 Function Progenitors.” The correct appears correction, and article has been updated online. 2015) Due A GlandShiah et al.Stem ReportsFebruary 19, 2015In BriefIn article, Khokha colleagues use expression profiling functional assays identify CXCR4, receptor for stromal-derived factor 1...