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SELECTBIO Conferences Circulating Biomarkers, Exosomes & Liquid Biopsy Asia 2019

Ramkumar Menon's Biography



Ramkumar Menon, Associate Professor, The University of Texas Medical Branch (UTMB)

Dr. Ramkumar Menon, is an Associate Professor (with tenure) in the Department of Obstetrics and Gynecology at The University of Texas Medical Branch (UTMB) at Galveston, Texas, USA. He joined UTMB in 2011. Dr. Menon is a Perinatal Reproductive Biologist, working in the field for the past 27 years, specifically in the area of spontaneous preterm birth and preterm premature rupture of the membranes. He received his under graduate degree in Medical Laboratory Technology (University of Kerala, India; 1998), Masters in Microbiology and Immunology (Wright State University, Dayton, OH, USA; 1993) and PhD in Perinatal Genetic Epidemiology (Arhus University, Arhus, Denmark; 2007). He served as director of the Perinatal Research Center in Nashville, TN, USA between 1995-2011. He is instrumental in establishing biobanks for studying genetic epidemiologic risk factors of preterm birth. Besides these studies, using human fetal membranes (amniochorion) as the model system, Dr. Menon has studied fetal immune response to various endogenous and exogenous risk exposures that can contribute to preterm birth. Dr. Menon reported telomere associated progressive development of human fetal membrane senescence during gestation that peaks at term corresponding with fetal growth. Recently, Dr. Menon’s laboratory has shown that senescence associated signals, primarily inflammatory signals, can propagate from fetal to maternal tissues to cause parturition associated inflammatory changes. This is considered as ‘biologic clock’ and a novel mechanism indicating fetal readiness for parturition. Dr. Menon has reported that propagation of senescence associated inflammation is primarily by extracellular vesicles, specifically exosomes. Extensive work using animal models by The Menon laboratory has reported feto-maternal communication via exosomes and how exosomes can trigger term and preterm parturition. The Menon laboratory is also exploring the usefulness of exosomes as biomarkers of preterm birth. Besides exosome based commination studies, senescent fetal membranes from The Menon laboratory has shown ‘microfractures’, structural alteration in fetal membranes that are likely site of cellular remodeling. Excessive number of microfractures are associated with fetal membrane rupture at term and preterm. Analysis of fetal membrane remodeling revealed inflammation and oxidative stress associated Epithelial Mesenchymal Transition (EMT) of fetal membrane amnion cells that are recycled back to epithelial cells to regenerate cellular gaps by progesterone mediated Mesenchymal Epithelial Transition (MET). Dr. Menon’s laboratory is funded by multiple grants from NIH as well as funds from March of Dimes, Bill and Melinda Gates Foundation among others. Dr. Menon is the Executive Director of Preterm Birth International Collaborative (PREBIC, Inc), a not for profit organization working to promote clinical translational research to reduce the risk of prematurity. Dr. Menon has authored/co-authored over 250 peer reviewed articles, reviews and book chapters.

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Role of Extracellular Vesicles as Communication Signals between Feto-Maternal Tissues

Tuesday, 10 September 2019 at 16:00

Add to Calendar ▼2019-09-10 16:00:002019-09-10 17:00:00Europe/LondonRole of Extracellular Vesicles as Communication Signals between Feto-Maternal TissuesCirculating Biomarkers, Exosomes and Liquid Biopsy Asia 2019 in Seoul, KoreaSeoul, KoreaSELECTBIOenquiries@selectbiosciences.com

During pregnancy, feto-maternal communication can be mediated through extracellular vesicles. Exosomes carry cellular signals and traffic between fetal and maternal tissues to produce functional changes in recipient cells. Exosomes may function as a biomarker indicative of the physiologic status of their tissue of origin. These properties of exosomes during pregnancy are not well studied. To test exosome trafficking and function, we utilized a transgenic mouse model containing membrane-targeted, red fluorescent protein tdTomato (mT) and enhanced green fluorescent protein (mG) Cyclic recombinase (Cre)-reporter construct expressed only in fetal tissues. This model allows fetal tissues and their exosomes to express mT under normal conditions or mG expression if fetal tissues are exposed to Cre that will excise mT. As maternal tissue remains negative for this construct, mT/mG expression and their switching can be utilized to determine fetal specific cell and exosome trafficking. mT/mG homozygous males were mated with wild type (WT) females to have all fetal tissues express the mT/mG allele.  Red florescence due to mT expression of the mT/mG allele in fetal tissues (placenta, fetal membranes) was confirmed by confocal microscopy on embryonic day (E) 16. Localization of fetal exosomes in maternal uterine tissues were performed by immunostaining for exosome marker CD81 and mT expression followed by confocal microscopy. Fetal exosomes (mT+) in maternal plasma were immunoprecipitated using anti-mT and followed by confirmation by flow cytometry.  To further illustrate the fidelity of fetal exosomes in maternal samples, exosomes bioengineered to contain Cre (1.0x1010 exosomes) were injected intraperitoneally (IP) on E13. On E16, fetal (placenta and fetal membranes) tissues were imaged to show mT to mG transition.mG expressing exomes were localized in maternal tissues (confocal microscopy) and plasma (flow cytometry). Mating between male with the mT/mG construct and null female resulted in fetal tissues and their exosomes expressing mT+.Total fetal exosomes in maternal plasma was about 35%. mT+ exosomes were isolated from maternal plasma and immunostaining localized mT+ exosomes in maternal uterine tissues. Maternal IP injection of Cre-enriched exosomes crossed placenta, excised mT from the mT/mG construct in the fetal tissues and caused mG expression in fetal cells. Further, mG+ exosomes released from fetal cells were isolated from maternal blood. Additionally, we show trafficking of mT+ fetal macrophage to maternal uterine tissues. We report feto-maternal and maternal-fetal trafficking of exosomes indicative of paracrine signaling during pregnancy. Exosomes from the maternal side can produce functional changes in fetal tissues. Trafficking of exosomes suggests their potential role in pregnancy as biomarkers of fetal functions and usefulness as a carrier of drugs and other cargo to the fetal side during pregnancy. Isolation and characterization of fetal exosomes can advance fetal research without performing invasive procedures.


Add to Calendar ▼2019-09-09 00:00:002019-09-10 00:00:00Europe/LondonCirculating Biomarkers, Exosomes and Liquid Biopsy Asia 2019Circulating Biomarkers, Exosomes and Liquid Biopsy Asia 2019 in Seoul, KoreaSeoul, KoreaSELECTBIOenquiries@selectbiosciences.com