Magee Womens Research Institute

Pittsburgh, PA, United States

Magee Womens Research Institute

Pittsburgh, PA, United States
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News Article | September 28, 2017

To advance ongoing and innovative research in women's health, a $1 million prize will be awarded to a team of top scientists at the inaugural 9-90™ Research Summit, taking place Oct. 8-10, 2018, in Pittsburgh. The international summit will bring together the world's leading women's health research scientists and thought leaders to establish a national agenda in women's reproductive sciences and health research, and will ignite the next generation of scientific leaders. The Richard King Mellon Foundation has funded the Magee Prize, supporting the Magee-Womens Research Institute (MWRI) mission and accomplishments, to change the way the world thinks about women's health. As the nation's largest research institute devoted exclusively to women's health research, MWRI scientists are focused on tackling some of the most problematic health issues facing women. "The earliest stages of development contribute to many diseases that affect humankind," said Michael Annichine, chief executive officer, MWRI. "Our initiative supports our 9-90™ movement -- that maternal and fetal health in the first 9 months of pregnancy can have a profound impact on the health and wellness of a person throughout the next 90 years of life." The Magee Prize will be awarded to a collaborative team of researchers from anywhere in the world who propose the best project in women's health research. The winners will be selected based on innovation and collaborative research in disciplines that include early human development, reproductive sciences and gender-based biology. The winners will collaborate with MWRI researchers to improve women's health around the globe. "If there were a Nobel Prize in women's health research, the Magee Prize would be it," said Carrie Coghill, chair of the MWRI board. "We will reward research that promises to discover new information and translate that research into treatment or disease prevention. MWRI envisions new thinking, new expectations, and a new approach to health care research and practice by raising women's health research and global collaboration to the prominence it deserves." The 9-90™ Research Summit will be an opportunity for the exchange of ideas and dialogue among biomedical women's health research experts, and seeks to bring about a movement that will solve some of the most vexing health issues, particularly focused on: "This landmark prize and summit will have an impact not only on the local and regional Pittsburgh community, but also on the national and global community," said Yoel Sadovsky, M.D., executive director of MWRI. "We firmly believe in our ability to stimulate 'science without borders,' reaching beyond Magee to the nation and the world." Magee-Womens Research Institute (MWRI) is the largest research institute in the US devoted exclusively to health conditions affecting women and infants. The Institute is leading discoveries and advancing knowledge in the field of reproductive biology and medicine, translating this knowledge into improved health, wellness and disease prevention for women, engaging our community in women's health, and training the present and future generations of women's health researchers. Researchers at Magee-Womens Research Institute are making discoveries and advancing knowledge in the field of reproductive biology and medicine, translating this knowledge into improved health, wellness and disease prevention for women and their infants. Some of the institute's most significant research initiatives include:

Mallipeddi R.,Magee Womens Research Institute | Mallipeddi R.,University of Pittsburgh | Rohan L.C.,Magee Womens Research Institute | Rohan L.C.,University of Pittsburgh
Expert Opinion on Drug Delivery | Year: 2010

Importance of the Field: Several strategies are being investigated for the prevention of heterosexual transmission of HIV. Of these, topical vaginal drug delivery systems, microbicides, are being actively pursued. HIV prevention by means of a topical microbicide has several drug delivery challenges. These challenges include the vaginal mucosal barriers and potential degradation of the drugs in the vaginal lumen due to pH and enzymes present. Also, new drugs being evaluated as microbicides have specific mechanisms of action, which in some cases require drug targeting to a specific site of action. Nanoparticles provide a delivery strategy for targeted or controlled delivery to the vagina which can be applied in the field of HIV prevention. Areas covered in the review: This review summarizes nanoparticulate systems and their use in mucosal delivery to date. The sexual transmission of HIV along with the various targets to prevent transmission are discussed as well as the potential opportunities, challenges and advantages in using a nanoparticle-based approach for microbicidal drug delivery. What the reader will gain: This review provides a general understanding of vaginal drug delivery, its challenges, and nanoparticulate delivery systems. Additionally, insight will be gained as to the limited existing application of this technology to the field of HIV prevention. Take home message: To date, few studies have been published that exploit nanoparticle-based microbicidal delivery to the vagina. The use of nanoparticles for vaginal drug delivery provides an approach to overcome the existing barriers to success. © 2010 Informa UK Ltd.

Yanowitz J.,Magee Womens Research Institute
Current Opinion in Cell Biology | Year: 2010

The perpetuation of most eukaryotic species requires differentiation of pluripotent progenitors into egg and sperm and subsequent fusion of these gametes to form a new zygote. Meiosis is a distinguishing feature of gamete formation as it leads to the twofold reduction in chromosome number thereby maintaining ploidy across generations. This process increases offspring diversity through the random segregation of chromosomes and the exchange of genetic material between homologous parental chromosomes, known as meiotic crossover recombination. These exchanges require the establishment of unique and dynamic chromatin configurations that facilitate cohesion, homolog pairing, synapsis, double strand break formation and repair. The precise orchestration of these events is critical for gamete survival as demonstrated by the majority of human aneuploidies that can be traced to defects in the first meiotic division (Hassold T, Hall H, Hunt P: The origin of human aneuploidy: where we have been, where we are going. Hum Mol Genet 2007, 16 Spec No. 2:R203-R208.). This review will focus on recent advances in our understanding of key meiotic events and how coordination of these events is occurring. © 2010 Elsevier Ltd.

Weissgerber T.L.,Magee Womens Research Institute | Davies G.A.L.,Queen's University | Tschakovsky M.E.,Queen's University
Journal of Applied Physiology | Year: 2010

Radial artery diameter decreases when a wrist cuff is inflated to stop blood flow to distal tissue. This phenomenon, referred to as low flow-mediated vasoconstriction (L-FMC), was proposed as a vascular function test. Recommendations that L-FMC be measured concurrently with flow-mediated dilation (FMD) were based on radial artery data. However, cardiovascular disease prediction studies traditionally measure brachial artery FMD. Therefore, studies should determine whether L-FMC occurs in the brachial artery. The hypothesis that reduced shear causes L-FMC has not been tested. Brachial and radial artery L-FMC and FMD were assessed in active nonpregnant (n = 17), inactive nonpregnant (n = 10), active pregnant (n = 15, 34.1 ± 1.2 wk gestation), and inactive pregnant (n = 8, 34.2 ± 2.2 wk gestation) women. Radial artery diameter decreased significantly during occlusion in all groups (nonpregnant, -4.4 ± 4.2%; pregnant, -6.4 ± 3.2%). Brachial artery diameter did not change in active and inactive nonpregnant, and inactive pregnant women; however, the small decrease in active pregnant women was significant. Occlusion decreased shear rate in both arteries, yet L-FMC only occurred in the radial artery. Radial artery L-FMC was not correlated with the reduction in shear rate. L-FMC occurs in the radial but not the brachial artery and is not related to changes in shear rate. Positive correlations between L-FMC (negative values) and FMD (positive values) suggest that radial artery FMD may be reduced among women who experience greater L-FMC. Studies should clarify the underlying stimulus and mechanisms regulating L-FMC, and test the hypothesis that endothelial dysfunction is manifested as enhanced brachial artery L-FMC, but attenuated radial artery L-FMC. Copyright © 2010 the American Physiological Society.

Majumdar S.S.,National Institute of Immunology | Sarda K.,National Institute of Immunology | Bhattacharya I.,National Institute of Immunology | Plant T.M.,Magee Womens Research Institute
Human Reproduction | Year: 2012

background: In humans, as well as in other higher primates, the infantile testis is exposed to an adult-like hormonal milieu, but spermatogenesis is not initiated at this stage of primate development. In the present study, we examined the molecular basis of this intriguing infertile state of the primate testis. methods: The integrity of androgen receptor (AR) and FSH receptor (FSHR) signaling pathways in primary cultures of Sertoli cells (Scs) harvested from azoospermic infant and spermatogenic pubertal monkey testes were investigated under identical in vitro hormonal conditions. In order to synchronously harvest Scs from early pubertal testis, the activation of testicular puberty was timed experimentally by prematurely initiating gonadotrophin secretion in juvenile animals with an intermittent infusion of gonadotrophin-releasing hormone. results: While qRT-PCR demonstrated that AR and FSHR mRNA expression in Scs from infant and pubertal testes were comparable, androgen-binding and FSH-mediated cAMP production by infant Scs was extremely low. Compromised AR and FSHR signaling in infant Scs was further supported by the finding that testosterone (T) and FSH failed to augment the expression of the T responsive gene, claudin 11, and the FSH responsive genes, inhibin-bB, stem cell factor (SCF) and glial cell line-derived neurotrophic factor (GDNF) in Scs harvested at this stage of development. conclusion: These results indicate that compromised AR and FSHR signaling pathways in Scs underlie the inability of the infant primate testis to respond to an endogenous hormonal milieu that later in development, at the time puberty, stimulates the initiation of spermatogenesis. This finding may have relevance to some forms of idiopathic infertility in men. © The Author 2012.

Burgener A.,Public Health Agency of Canada | Burgener A.,University of Manitoba | Burgener A.,Karolinska Institutet | McGowan I.,University of Pittsburgh | And 3 more authors.
Current Opinion in Immunology | Year: 2015

The mucosal barrier plays an integral function in human health as it is the primary defense against pathogens, and provides a critical transition between the external environment and the human internal body. In the context of HIV infection, the most relevant mucosal surfaces include those of the gastrointestinal (GI) and genital tract compartments. Several components help maintain the effectiveness of this mucosal surface, including the physical anatomy of the barrier, cellular immunity, soluble factors, and interactions between the epithelial barrier and the local microenvironment, including mucus and host microbiota. Any defects in barrier integrity or function can rapidly lead to an increase in acquisition risk, or with established infection may result in increased pathogenesis, morbidities, or mortality. Indeed, a key feature to all aspects of HIV infection from transmission to pathogenesis is disruption and/or dysfunction of mucosal barriers. Herein, we will detail the host-pathogen relationship of HIV and mucosal barriers in both of these scenarios. © 2015.

Roberts J.M.,Magee Womens Research Institute | Roberts J.M.,University of Pittsburgh
Seminars in Perinatology | Year: 2014

The pregnancy disorders associated with placental ischemia share many similar pathological and pathophysiological features and are associated with the failure to deliver adequate nutrients and oxygen to the placenta. The origins of this deficiency are a subject of intense study. In this article, I review the genesis and consequences of this pathology addressing the similarities and the differences with the different disorders and addressing current gaps in our knowledge. © 2014 Elsevier Inc.

Wong J.L.,University of Pittsburgh | Berk E.,University of Pittsburgh | Edwards R.P.,Peritoneal Ovarian Cancer Specialty Care Center | Edwards R.P.,University of Pittsburgh | And 2 more authors.
Cancer Research | Year: 2013

Chemokine-driven interactions of immune cells are essential for effective antitumor immunity. Human natural killer (NK) cells can be primed by the interleukin (IL)-1-related proinflammatory cytokine IL-18 for unique helper activity, which promotes dendritic cell (DC) activation and DC-mediated induction of type-1 immune responses against cancer. Here, we show that such IL-18-primed "helper" NK cells produce high levels of the immature DC (iDC)-attracting chemokines CCL3 and CCL4 upon exposure to tumor cells or the additional inflammatory signals IFN-a, IL-15, IL-12, or IL-2. These "helper" NK cells potently attract iDCs in a CCR5-dependent mechanism and induce high DC production of CXCR3 and CCR5 ligands (CXCL9, CXCL10, and CCL5), facilitating the subsequent recruitment of type-1 effector CD8 + T (Teff) cells. Using cells isolated from the malignant ascites of patients with advanced ovarian cancer, we show that "helper" NK cell-inducing factors can be used to enhance local production of Teff cell-recruiting chemokines. Our findings reveal the unique chemokine expression profile of "helper"NK cells and highlight the potential for using two-signal-activated NKcells to promote homing of type- 1 immune effectors to the human tumor environment. © 2013 American Association for Cancer Research.

Bodnar L.M.,University of Pittsburgh | Simhan H.N.,University of Pittsburgh | Simhan H.N.,Magee Womens Research Institute
Obstetrical and Gynecological Survey | Year: 2010

In the United States, significant, intractable disparities exist in rates of major pregnancy outcomes between non-Hispanic black and non-Hispanic white women. A previously unexplored candidate influence on the black-white disparity in adverse birth outcomes is maternal vitamin D status. This review summarizes the evidence relating maternal vitamin D to preeclampsia, spontaneous preterm birth, gestational diabetes, and fetal growth restriction, and addresses gaps in our understanding of the contribution of vitamin D to the intractable black-white disparity in these conditions. The literature reviewed highlights strong biologic plausibility of role for vitamin D in the pathophysiology of these poor pregnancy outcomes. Data also suggest that maternal vitamin D deficiency may increase the risk of preeclampsia and fetal growth restriction. Less research has been done in support of relations with spontaneous preterm birth and gestational diabetes, and fetal and infant survival have rarely been studied. Few trials of vitamin D supplementation have been conducted in pregnant women with adequate power to test effects on birth outcomes. Importantly, black pregnant women have rarely been studied in vitamin D-birth outcomes research. Although vitamin D is a promising candidate influence on black-white disparities in preeclampsia, spontaneous preterm birth, fetal growth restriction, and gestational diabetes, these associations require further study in large samples of black US women. Because vitamin D deficiency is widespread and black-white disparities in pregnancy outcomes and infant survival have been resistant to previous interventions, research to test vitamin D as a causal factor is of major public health significance. Target Audience: Obstetricians & Gynecologist, Family Physicians. Learning Objectives: After completion of this educational activity, the reader will be able to appreciate risk factors for inadequate vitamin D status. Understand the basic aspects of vitamin D metabolism. Become aware of recent literature linking inadequate vitamin D status and adverse pregnancy outcomes such as preeclampsia and preterm birth. © 2010 by Lippincott Williams & Wilkins.

Obermajer N.,University of Pittsburgh | Muthuswamy R.,University of Pittsburgh | Lesnock J.,Magee Womens Research Institute | Edwards R.P.,Magee Womens Research Institute | And 2 more authors.
Blood | Year: 2011

Dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) show opposing roles in the immune system. In the present study, we report that the establishment of a positive feedback loop between prostaglandin E2 (PGE2) and cyclooxygenase 2 (COX2), the key regulator of PGE 2synthesis, represents the determining factor in redirecting the development of CD1a+ DCs to CD14+CD33+CD34 + monocytic MDSCs. Exogenous PGE2 and such diverse COX2 activators as lipopolysaccharide, IL-1β, and IFNγ all induce monocyte expression of COX2, blocking their differentiation into CD1a+ DCs and inducing endogenous PGE2, IDO1, IL-4Rα, NOS2, and IL-10, typical MDSC-associated suppressive factors. The addition of PGE2 to GM-CSF/IL-4-supplemented monocyte cultures is sufficient to induce the MDSC phenotype and cytotoxic T lymphocyte (CTL)-suppressive function. In accordance with the key role of PGE2 in the physiologic induction of human MDSCs, the frequencies of CD11b+CD33+ MDSCs in ovarian cancer are closely correlated with local PGE2 production, whereas the cancer-promoted induction of MDSCs is strictly COX2 dependent. The disruption of COX2-PGE2 feedback using COX2 inhibitors or EP2 and EP4 antagonists suppresses the production of MDSC-associated suppressive factors and the CTL-inhibitory function of fully developed MDSCs from cancer patients. The central role of COX2-PGE2 feedback in the induction and persistence of MDSCs highlights the potential for its manipulation to enhance or suppress immune responses in cancer, autoimmunity, or transplantation. © 2011 by The American Society of Hematology.

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