Alexander G Beristain

Alexander G Beristain
University of British Columbia - Vancouver | UBC · Department of Obstetrics and Gynaecology

PhD

About

55
Publications
4,459
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1,522
Citations
Citations since 2016
31 Research Items
973 Citations
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2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
Introduction
Alexander G Beristain currently works at the Department of Obstetrics and Gynaecology, University of British Columbia - Vancouver. Alexander does research in trophoblast differentiation and function, and the role of the maternal immune system in pregnancy.
Additional affiliations
July 2007 - July 2012
University Health Network
Position
  • PostDoc Position
Description
  • Cancer biology lab examining signal transduction pathways in bone and breast tumor development

Publications

Publications (55)
Preprint
Full-text available
The recent discovery of human trophoblast stem cells (hTSC) and techniques allowing for trophoblast organoid (TOrg) culture have established promising approaches for studying human trophoblast development. To validate the accuracy of these models at single-cell resolution, we directly compared in vitro TOrg cultures derived from primary progenitor...
Article
The metzincin family of metalloproteases coordinates tissue developmental processes through regulation of growth factor availability, receptor signaling, and cell-cell/cell-matrix adhesion. While roles for select metzincins in controlling trophoblast functions in human placental development have been described, a comprehensive understanding of metz...
Preprint
Full-text available
The metzincin family of metalloproteases coordinates cell and tissue developmental processes through regulation of growth factor availability, receptor signaling, and cell-cell/cell-matrix adhesion. During placental development, while distinct roles for metzincin proteases in controlling specific trophoblast functions have been described, a compreh...
Preprint
Full-text available
In early pregnancy, macrophages (Mφ) and natural killer cells (NK) infiltrate and expand within the decidua to comprise 30% of all cellular content. These immune cell populations coordinate angiogenic and tissue remodeling processes that are needed for a healthy pregnancy. Importantly, decidual tissue-resident macrophages (trMφ) and uterine NK reta...
Article
In early placental development, progenitor cytotrophoblasts (CTB) differentiate along one of two cellular trajectories: the villous or extravillous pathways. CTB committed to the villous pathway fuse with neighboring CTB to form the outer multinucleated syncytiotrophoblast (SCT), whereas CTB committed to the extravillous pathway differentiate into...
Preprint
Full-text available
In early placental development, progenitor cytotrophoblasts (CTBs) differentiate along one of two cellular trajectories: the villous or extravillous pathways. CTBs committed to the villous pathway fuse with neighboring CTBs to form the outer multinucleated syncytiotrophoblast (SCT), while CTBs committed to the extravillous pathway differentiate int...
Article
Full-text available
Background DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester ( n = 9) and term ( n...
Article
Full-text available
Adequate anchoring of the placenta in the uterus through invasion of first trimester cytotrophoblasts (CTB) is required for a successful pregnancy. This process is mediated by matrix metalloproteinases (MMPs) and regulated by the maternal environment. Obesity is known to alter the intrauterine milieu and has been related to impaired invasion. We hy...
Preprint
Full-text available
Background DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n = 9) and term (n =...
Preprint
Full-text available
Background: DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n=9) and term (n=19...
Preprint
Full-text available
Background: DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n=9) and term (n=19...
Article
Full-text available
Inflammation is often equated to the physiological response to injury or infection. Inflammatory responses defined by cytokine storms control cellular mechanisms that can either resolve quickly (i.e., acute inflammation) or remain prolonged and unabated (i.e., chronic inflammation). Perhaps less well-appreciated is the importance of inflammatory pr...
Article
Early placental development and the establishment of the invasive trophoblast lineage take place within a low oxygen environment. However, conflicting and inconsistent findings have obscured the role of oxygen in regulating invasive trophoblast differentiation. In this study, the effect of hypoxic, normoxic, and atmospheric oxygen on invasive extra...
Article
Pre-pregnancy obesity associates with adverse reproductive outcomes that impact maternal and fetal health. While obesity-driven mechanisms underlying adverse pregnancy outcomes remain unclear, local uterine immune cells are strong but poorly studied candidates. Uterine immune cells, particularly uterine natural killer cells (uNK), play central role...
Preprint
Full-text available
Early placental development and the establishment of the invasive trophoblast lineage take place within a low oxygen environment. However, conflicting and inconsistent findings have obscured the role of oxygen in regulating invasive trophoblast differentiation. In this study, the effect of hypoxic, normoxic, and atmospheric oxygen on invasive extra...
Article
Full-text available
During placentation invasive extravillous trophoblasts (EVTs) migrate into the maternal uterus and modify its vessels. In particular, remodeling of the spiral arteries by EVTs is critical for adapting blood flow and nutrient transport to the developing fetus. Failures in this process have been noticed in different pregnancy complications such as pr...
Article
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Study question: Does A Disintegrin And Metalloproteinase 8 (ADAM8) control extravillous trophoblast (EVT) differentiation and migration in early human placental development? Summary answer: ADAM8 mRNA preferentially localizes to invasive HLA-G-positive trophoblasts, associates with the acquirement of an EVT phenotype, and promotes trophoblast mi...
Article
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In pregnancy, uterine natural killer cells (uNK) play essential roles in coordinating uterine angiogenesis, blood vessel remodeling, and promoting maternal tolerance to fetal tissue. Deviances from a normal uterine microenvironment are thought to modify uNK function(s) by limiting their ability to establish a healthy pregnancy. While maternal obesi...
Preprint
Full-text available
Baltayeva et al 1 1 A mouse model of maternal obesity leads to uterine natural killer (uNK) cell activation and 2 uterine artery remodeling defects 3 4 ABSTRACT 1 Maternal obesity associates with multiple adverse reproductive outcomes, negatively affecting the 2 health and survival of both the mother and the fetus. The contributory effects of obesi...
Preprint
Full-text available
In pregnancy, uterine natural killer cells (uNK) play essential roles in coordinating uterine angiogenesis, blood vessel remodeling, and promoting maternal tolerance to fetal tissue. Deviances from a normal uterine microenvironment are thought to modify uNK function(s), limiting their ability to establish a healthy pregnancy. While maternal obesity...
Article
Introduction Trophoblast progenitor cell differentiation towards the extravillous trophoblast (EVT) lineage initiates within proximal regions of anchoring columns of first trimester placental villi. While molecular processes controlling the initial stages of progenitor cell differentiation along the EVT pathway have been described, much remains unk...
Article
Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialised topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of decidual-trophoblast interaction, regul...
Article
Full-text available
Over one-fifth of North American women of childbearing age are obese, putting these women at risk for a variety of detrimental chronic diseases. In addition, obesity increases the risk for developing major complications during pregnancy. The mechanisms by which obesity contributes to pregnancy complications and loss remain unknown. Increasing evide...
Article
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Proper placental development and function is crucial for a healthy pregnancy, and there has been substantial research to identify markers of placental dysfunction for the early detection of pregnancy complications. Low first-trimester levels of a disintegrin and metalloproteinase 12 (ADAM12) and pregnancy-associated plasma protein-A (PAPP-A) have b...
Article
Trophoblasts, placental cells of epithelial lineage, undergo extensive differentiation to form the cellular components of the placenta. Trophoblast progenitor cell differentiation into the multinucleated syncytiotrophoblast is a key developmental process required for placental function, where defects in syncytiotrophoblast formation and turnover as...
Article
Full-text available
Progesterone drives mammary stem and progenitor cell dynamics through paracrine mechanisms that are currently not well understood. Here, we demonstrate that CXCR4, the receptor for stromal-derived factor 1 (SDF-1; CXC12), is a crucial instructor of hormone-induced mammary stem and progenitor cell function. Progesterone elicits specific changes in t...
Article
Placental development is a highly regulated process requiring signals from both fetal and maternal uterine compartments. Within this complex system, trophoblasts, placental cells of epithelial lineage, form the maternal-fetal interface controlling nutrient, gas and waste exchange. The commitment of progenitor villous cytotrophoblasts to differentia...
Article
Full-text available
Adverse gestational outcomes such as preeclampsia (PE) and intrauterine growth restriction (IUGR) are associated with placental insufficiency. Normal placental development relies on the insulin-like growth factors -I and -II (IGF-I and -II), in part to stimulate trophoblast proliferation and extravillous trophoblast (EVT) migration. The insulin-lik...
Article
Full-text available
Protein kinase A (PKA) hyperactivation causes hereditary endocrine neoplasias; however, its role in sporadic epithelial cancers is unknown. Here, we show that heightened PKA activity in the mammary epithelium generates tumors. Mammary-restricted biallelic ablation of Prkar1a, which encodes for the critical type-I PKA regulatory subunit, induced spo...
Article
Full-text available
Increasingly, placental DNA methylation is assessed as a factor in pregnancy-related complications; yet the transcriptional impact of such findings are not always clear. Using a proliferative in vitro placental model, the effect of DNA methylation loss on gene activation was evaluated at a number of genes selected for being differentially methylate...
Article
Full-text available
During pregnancy, stromal- and vascular-remodeling trophoblasts serve critical roles in directing placental development acquiring pro-invasive characteristics. The A Disintegrin and Metalloproteinase (ADAM) family of multifunctional proteins direct cellular processes across multiple organ systems via their intrinsic catalytic, cell adhesive and int...
Article
Lifetime exposure to ovarian hormones plays a crucial role in determining a woman's risk for breast cancer: the risk of developing breast cancer is positively correlated with the number of ovarian-hormone-dependent menstrual cycles. Progesterone is an ovarian steroid hormone that peaks during the luteal phase of the female menstrual cycle. Recent r...
Article
Full-text available
RANKL (receptor activator of NF-κB ligand) is a crucial cytokine for regulating diverse biological systems such as innate immunity, bone homeostasis and mammary gland differentiation, operating through activation of its cognate receptor RANK. In these normal physiological processes, RANKL signals through paracrine and/or heterotypic mechanisms wher...
Data
ADAMTS-12 does not regulate the expression of a subset of ECM proteins. Ethidium bromide-stained photographs of RT-PCR products generated using primers specific to the ECM proteins vitronectin (V), fibronectin (F), laminin (L) and tenascin (T) and the housekeeping gene GAPDH from cDNA's made from (A) JEG-3 cells stably transfected with ADAMTS-12 (A...
Data
ADAMTS-12 does not associate with the αv integrin. αv integrin was immunoprecipitated from protein lysates of JEG-3 cells stably transfected with LacZ (lanes 1 and 2), A12FL (lanes 3 and 4) or A12Mut (lanes 5 and 6). Immunoprecipitates (IP) were probed for with antibodies directed against ADAMTS-12 (A) and αv integrin (B). Representative autoradiog...
Data
Exogenous ADAMTS-12 does not alter cellular aggregation. Photomicrographs show JEG-3 cells stably transfected with pcDNA3-ADAM-TS12 (A12FL), pcDNA3-ADAM-TS12-MUT (A12Mut) or pcDNA3-LacZ (LacZ) that were cultured in 20 µl hanging drops for 2 or 8 h prior to being inverted and mounted with a glass cover slip. The histogram quantitatively describes ce...
Data
Names of genes, DNA primer sequences and PCR conditions for the semiquantitative analysis of levels of mRNA transcripts for ADAMTS, integrin and ECM genes in human placental tissue and trophoblastic cells. (DOC)
Article
Full-text available
Metastatic carcinoma cells exploit the same molecular machinery that allows human placental cytotrophoblasts to develop an invasive phenotype. As altered expression levels of ADAMTS (ADisintegrin And Metalloproteinase with ThromboSpondin repeats) subtypes have been associated with cancer progression, we have examined the function and regulation of...
Article
Full-text available
Some cancers have been stratified into subclasses based on their unique involvement of specific signaling pathways. The mapping of human cancer genomes is revealing a vast number of somatic alterations; however, the identification of clinically relevant molecular tumor subclasses and their respective driver genes presents challenges. This informati...
Article
Full-text available
Reproductive history is the strongest risk factor for breast cancer after age, genetics and breast density. Increased breast cancer risk is entwined with a greater number of ovarian hormone-dependent reproductive cycles, yet the basis for this predisposition is unknown. Mammary stem cells (MaSCs) are located within a specialized niche in the basal...
Article
s: First AACR International Conference on Frontiers in Basic Cancer Research--Oct 8–11, 2009; Boston MA Osteosarcoma is the most common bone tumor in adolescents, severely impacts quality of life, and ∼40% of patients die of metastases to lungs and liver. In an effort to study this poorly understood cancer, we have generated a novel transgenic mou...
Article
Full-text available
There is increasing evidence to suggest that the classical form of GnRH (GnRH I) and the second mammalian form of this hormone, GnRH II, play regulatory roles in human implantation and placentation. To date, the cellular distribution of these two hormones at the maternal-fetal interface remains poorly characterized. In these studies, we localized G...
Article
Full-text available
Extensive remodeling of the extracellular matrix occurs in the ovary during the periovulatory period. Matrix metalloproteinases and their endogenous inhibitors, tissue inhibitors of metalloproteinases, are believed to play integral roles in this highly regulated series of cellular events, but their specific roles remain unclear. Recent cloning stud...

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