Medical Cell Biology Commons^™

A Non-Coding Insertional Mutation Of Grhl2 Causes Gene Over-Expression And Multiple Structural Anomalies Including Cleft Palate, Spina Bifida And Encephalocele, Zoe Crane-Smith, Sandra C P De Castro, Evanthia Nikolopoulou, Paul Wolujewicz, Damian Smedley, Yunping Lei, Emma Mather, Chloe Santos, Mark Hopkinson, Andrew A Pitsillides, Richard H Finnell, M Elisabeth Ross, Andrew J Copp, Nicholas D E Greene

Faculty, Staff and Students Publications

Orofacial clefts, including cleft lip and palate (CL/P) and neural tube defects (NTDs) are among the most common congenital anomalies, but knowledge of the genetic basis of these conditions remains incomplete. The extent to which genetic risk factors are shared between CL/P, NTDs and related anomalies is also unclear. While identification of causative genes has largely focused on coding and loss of function mutations, it is hypothesized that regulatory mutations account for a portion of the unidentified heritability. We found that excess expression of Grainyhead-like 2 (Grhl2) causes not only spinal NTDs in Axial defects (Axd) mice but also multiple …

Multiomic Investigations Into Lung Health And Disease, Sarah E Blutt, Cristian Coarfa, Josef Neu, Mohan Pammi

Faculty, Staff and Students Publications

Diseases of the lung account for more than 5 million deaths worldwide and are a healthcare burden. Improving clinical outcomes, including mortality and quality of life, involves a holistic understanding of the disease, which can be provided by the integration of lung multi-omics data. An enhanced understanding of comprehensive multiomic datasets provides opportunities to leverage those datasets to inform the treatment and prevention of lung diseases by classifying severity, prognostication, and discovery of biomarkers. The main objective of this review is to summarize the use of multiomics investigations in lung disease, including multiomics integration and the use of machine learning …

The Co-Oncogenic Function Of Ecdysoneless Protein With Erbb2 In Mammary Epithelial Cells, Benjamin B. Kennedy

Theses & Dissertations

The Ecdysoneless (ECD) protein is highly evolutionarily conserved and ubiquitously expressed across human tissues. ECD has established roles in cell cycle regulation, embryogenesis, cell survival, and RNA biogenesis. ECD mRNA and protein are overexpressed in breast cancer, and its overexpression correlates with poor patient survival, especially in ErbB2/HER2-positive breast cancer. This thesis work investigates the co-oncogenic role of ECD in ErbB2-driven oncogenesis using immortalized mammary epithelial cells. Here, we show that ECD and ErbB2 overexpression in immortalized human mammary epithelial cells increases cancer traits, such as invasion, migration, and anchorage independent growth. Significantly, ECD+ErbB2 co-overexpression further enhanced all oncogenic traits. …

Author Correction: Membrane Translocation Process Revealed By In Situ Structures Of Type Ii Secretion System Secretins, Zhili Yu, Yaoming Wu, Muyuan Chen, Tong Huo, Wei Zheng, Steven J Ludtke, Xiaodong Shi, Zhao Wang

Faculty, Staff and Students Publications

No abstract provided.

Loss Of Microrna-30a And Sex-Specific Effects On The Neonatal Hyperoxic Lung Injury, Sandra L Grimm, Samuel Reddick, Xiaoyu Dong, Connor Leek, Amy Xiao Wang, Manuel Cantu Gutierrez, Sean M Hartig, Bhagavatula Moorthy, Cristian Coarfa, Krithika Lingappan

Faculty, Staff and Students Publications

BACKGROUND: Bronchopulmonary dysplasia (BPD) is characterized by an arrest in lung development and is a leading cause of morbidity in premature neonates. It has been well documented that BPD disproportionally affects males compared to females, but the molecular mechanisms behind this sex-dependent bias remain unclear. Female mice show greater preservation of alveolarization and angiogenesis when exposed to hyperoxia, accompanied by increased miR-30a expression. In this investigation, we tested the hypothesis that loss of miR-30a would result in male and female mice experiencing similar impairments in alveolarization and angiogenesis under hyperoxic conditions.

METHODS: Wild-type and miR-30a−/− neonatal mice were exposed …

Role Of Phosphorylated Dicer1 In Tumor Progression, Raisa Reyes-Castro

Dissertations and Theses (Open Access)

DICER1 is a multidomain enzyme discovered and widely recognized for its function in small non-coding microRNA (miRNA) synthesis. In cancer development, DICER1 functions as a haploinsufficient tumor suppressor which regulates miRNAs and Epithelial-to-Mesenchymal Transition (EMT). The Arur laboratory discovered that DICER1 is phosphorylated by active ERK and that ERK-mediated phosphorylation triggers DICER1 to translocate from the cytoplasm to the nucleus of cells in worms, mice and humans. Further, a heterozygous allele of a genetically engineered mouse model of phosphomimetic Dicer1 when combined with heterozygous Kras oncogenic background contributes to lung tumor progression in vivo. Mechanisms through which phosphomimetic Dicer1 …

Chromatin Architectural Factor Ctcf Is Essential For Progesterone-Dependent Uterine Maturation, Sylvia C Hewitt, Artiom Gruzdev, Cynthia J Willson, San-Pin Wu, John P Lydon, Niels Galjart, Francesco J Demayo

Faculty, Staff and Students Publications

Receptors for estrogen and progesterone frequently interact, via Cohesin/CTCF loop extrusion, at enhancers distal from regulated genes. Loss-of-function CTCF mutation in >20% of human endometrial tumors indicates its importance in uterine homeostasis. To better understand how CTCF-mediated enhancer-gene interactions impact endometrial development and function, the Ctcf gene was selectively deleted in female reproductive tissues of mice. Prepubertal Ctcf

Deconvolution Of Cancer Cell States By The Xdec-Sm Method, Oscar D Murillo, Varduhi Petrosyan, Emily L Laplante, Lacey E Dobrolecki, Michael T Lewis, Aleksandar Milosavljevic

Faculty, Staff and Students Publications

Proper characterization of cancer cell states within the tumor microenvironment is a key to accurately identifying matching experimental models and the development of precision therapies. To reconstruct this information from bulk RNA-seq profiles, we developed the XDec Simplex Mapping (XDec-SM) reference-optional deconvolution method that maps tumors and the states of constituent cells onto a biologically interpretable low-dimensional space. The method identifies gene sets informative for deconvolution from relevant single-cell profiling data when such profiles are available. When applied to breast tumors in The Cancer Genome Atlas (TCGA), XDec-SM infers the identity of constituent cell types and their proportions. XDec-SM also …

Spatial Mapping Of The Dna Adducts In Cancer, Kimiko L Krieger, Elise K Mann, Kevin J Lee, Elyse Bolterstein, Deborah Jebakumar, Michael M Ittmann, Valeria L Dal Zotto, Mohamed Shaban, Arun Sreekumar, Natalie R Gassman

Faculty, Staff and Students Publications

DNA adducts and strand breaks are induced by various exogenous and endogenous agents. Accumulation of DNA damage is implicated in many disease processes, including cancer, aging, and neurodegeneration. The continuous acquisition of DNA damage from exogenous and endogenous stressors coupled with defects in DNA repair pathways contribute to the accumulation of DNA damage within the genome and genomic instability. While mutational burden offers some insight into the level of DNA damage a cell may have experienced and subsequently repaired, it does not quantify DNA adducts and strand breaks. Mutational burden also infers the identity of the DNA damage. With advances …

Loss Of Cytochrome P450 (Cyp)1b1 Mitigates Hyperoxia Response In Adult Mouse Lung By Reprogramming Metabolism And Translation, Sandra L Grimm, Rachel E Stading, Matthew J Robertson, Tanmay Gandhi, Chenlian Fu, Weiwu Jiang, Guobin Xia, Krithika Lingappan, Cristian Coarfa, Bhagavatula Moorthy

Faculty, Staff and Students Publications

Oxygen supplementation is life saving for premature infants and for COVID-19 patients but can induce long-term pulmonary injury by triggering inflammation, with xenobiotic-metabolizing CYP enzymes playing a critical role. Murine studies showed that CYP1B1 enhances, while CYP1A1 and CYP1A2 protect from, hyperoxic lung injury. In this study we tested the hypothesis that Cyp1b1-null mice would revert hyperoxia-induced transcriptomic changes observed in WT mice at the transcript and pathway level. Wild type (WT) C57BL/6J and Cyp1b1-null mice aged 8-10 weeks were maintained in room air (21% O

Trim28 Modulates Nuclear Receptor Signaling To Regulate Uterine Function, Rong Li, Tianyuan Wang, Ryan M Marquardt, John P Lydon, San-Pin Wu, Francesco J Demayo

Faculty, Staff and Students Publications

Estrogen and progesterone, acting through their cognate receptors the estrogen receptor α (ERα) and the progesterone receptor (PR) respectively, regulate uterine biology. Using rapid immunoprecipitation and mass spectrometry (RIME) and co-immunoprecipitation, we identified TRIM28 (Tripartite motif containing 28) as a protein which complexes with ERα and PR in the regulation of uterine function. Impairment of TRIM28 expression results in the inability of the uterus to support early pregnancy through altered PR and ERα action in the uterine epithelium and stroma by suppressing PR and ERα chromatin binding. Furthermore, TRIM28 ablation in PR-expressing uterine cells results in the enrichment of a …

Effect Of Exogenous L-Carnitine On Aortic Stiffness In Dyslipidemic Adolescents: Design Of A Quadruple-Blind, Randomized, Controlled Interventional Trial, Justin P Zachariah, Sandra Pena, Philip J Lupo, Nagireddy Putluri, Daniel J Penny, Melissa A Richard

Faculty, Staff and Students Publications

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) risk factors including vascular remodeling leading to hypertension and dyslipidemia are prevalent among children and adolescents. Conflicting observational and Mendelian randomization data suggest endogenous carnitine may affect arterial stiffness and lipid traits. Because of this, we developed a study to evaluate the causal role for carnitine in arterial stiffness at a point when the lifecourse trajectory to hypertension can be modified.

METHODS: This study is a mechanistic, double-blinded, randomized control trial (RCT) in 166 adolescents with dyslipidemia for the effect of 6 months of maximum dose 3 g daily oral l-carnitine supplementation (CS+) versus placebo …

Hunger Extends Lifespan By Modulating Histone Proteins, Hailan Liu, Hongjie Li, Yong Xu

Faculty, Staff and Students Publications

No abstract provided.

Increased Sirt3 Combined With Parp Inhibition Rescues Motor Function Of Sbma Mice, David R. Garcia Castro, Joseph R. Mazuk, Erin M. Heine, Daniel Simpson, R. Seth Pinches, Caroline Lozzi, Kathryn Hoffman, Phillip Morrin, Dylan Mathis, Maria V. Lebedev, Elyse Nissley, Kang Hoo Han, Tyler Farmer, Diane E. Merry, Qiang Tong, Maria Pennuto, Heather L. Montie

Department of Biochemistry and Molecular Biology Faculty Papers

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease with substantial mitochondrial and metabolic dysfunctions. SBMA is caused by polyglutamine (polyQ) expansion in the androgen receptor (AR). Activating or increasing the NAD+-dependent deacetylase, SIRT3, reduced oxidative stress and death of cells modeling SBMA. However, increasing diminished SIRT3 in AR100Q mice failed to reduce acetylation of the SIRT3 target/antioxidant, SOD2, and had no effect on increased total acetylated peptides in quadriceps. Yet, overexpressing SIRT3 resulted in a trend of motor recovery, and corrected TCA cycle activity by decreasing acetylation of SIRT3 target proteins. We sought to boost blunted SIRT3 activity …

Myc Regulates Csf1 Expression Via Microrna 17/20a To Modulate Tumor-Associated Macrophages In Osteosarcoma, Bikesh K Nirala, Tajhal D Patel, Lyazat Kurenbekova, Ryan Shuck, Atreyi Dasgupta, Nino Rainusso, Cristian Coarfa, Jason T Yustein

Faculty, Staff and Students Publications

Osteosarcoma (OS) is the most common primary bone tumor of childhood. Approximately 20%-30% of OSs carry amplification of chromosome 8q24, which harbors the oncogene c-MYC and correlates with a poor prognosis. To understand the mechanisms that underlie the ability of MYC to alter both the tumor and its surrounding tumor microenvironment (TME), we generated and molecularly characterized an osteoblast-specific Cre-Lox-Stop-Lox-c-MycT58A p53fl/+ knockin genetically engineered mouse model (GEMM). Phenotypically, the Myc-knockin GEMM had rapid tumor development with a high incidence of metastasis. MYC-dependent gene signatures in our murine model demonstrated significant homology to the human hyperactivated MYC OS. We established that …

Unravelling Spatial Gene Associations With Seagal: A Python Package For Spatial Transcriptomics Data Analysis And Visualization, Linhua Wang, Chaozhong Liu, Yang Gao, Xiang H-F Zhang, Zhandong Liu

Faculty, Staff and Students Publications

SUMMARY: In the era where transcriptome profiling moves toward single-cell and spatial resolutions, the traditional co-expression analysis lacks the power to fully utilize such rich information to unravel spatial gene associations. Here, we present a Python package called Spatial Enrichment Analysis of Gene Associations using L-index (SEAGAL) to detect and visualize spatial gene correlations at both single-gene and gene-set levels. Our package takes spatial transcriptomics datasets with gene expression and the aligned spatial coordinates as input. It allows for analyzing and visualizing genes' spatial correlations and cell types' colocalization within the precise spatial context. The output could be visualized as …

A Crispr/Cas9-Engineered Mouse Carrying A Conditional Knockout Allele For The Early Growth Response-1 Transcription Factor, Vineet K Maurya, Yan Ying, Denise G Lanza, Jason D Heaney, John P Lydon

Faculty, Staff and Students Publications

Early growth response 1 (EGR1) mediates transcriptional programs that are indispensable for cell division, differentiation and apoptosis in numerous physiologies and pathophysiologies. Whole-body EGR1 knockouts in mice (Egr1KO) have advanced our understanding of EGR1 function in an in vivo context. To extend the utility of the mouse to investigate EGR1 responses in a tissue- and/or cell-type-specific manner, we generated a mouse model in which exon 2 of the mouse Egr1 gene is floxed by CRISPR/Cas9 engineering. The floxed Egr1 alleles (Egr1f/f) are designed to enable spatiotemporal control of Cre-mediated EGR1 ablation in the …

Vincristine/Irinotecan/Temsirolimus Upfront Window Treatment Of High-Risk Hepatoblastoma: A Report From The Children’S Oncology Group Ahep0731 Study Committee, Patrick A Thompson, Marcio H Malogolowkin, Wayne L Furman, Jin Piao, Mark D Krailo, Nadia Chung, Lindsay Brock, Alexander J Towbin, Elizabeth B Mccarville, Milton J Finegold, Sarangarajan Ranganathan, Stephen P Dunn, Max R Langham, Eugene D Mcgahren, Gregory M Tiao, Christopher B Weldon, Allison F O'Neill, Carlos Rodriguez-Galindo, Rebecka L Meyers, Howard M Katzenstein

Faculty, Staff and Students Publications

Background: Survival for children with metastatic hepatoblastoma (HB) remains suboptimal. We report the response rate and outcome of two courses of vincristine/irinotecan/temsirolimus (VIT) in children with high-risk (HR)/metastatic HB.

Procedures: Patients with newly diagnosed HB received HR window chemotherapy if they had metastatic disease or a serum alpha-fetoprotein (AFP) level less than 100 ng/mL. Patients received vincristine (days 1 and 8), irinotecan (days 1-5), and temsirolimus (days 1 and 8). Cycles were repeated every 21 days. Responders had either a 30% decrease using RECIST (Response Evaluation Criteria in Solid Tumors) criteria OR a 90% (>1 log10 decline) AFP decline …

Longitudinal Analysis Of The Evolution Of Cellular Immunity To Sars-Cov-2 Induced By Infection And Vaccination, Spyridoula Vasileiou, Manik Kuvalekar, Yovana Velazquez, Ayumi Watanabe, Mansi Narula, Aster G Workineh, Matthew French-Kim, Alejandro Torres Chavez, Sarah Gilmore, Cliona M Rooney, Ann M Leen

Faculty, Staff and Students Publications

No abstract provided.

Dual Functions Of Tet1 In Germ Layer Lineage Bifurcation Distinguished By Genomic Context And Dependence On 5-Methylcytosine Oxidation, Bernard K Van Der Veer, Lehua Chen, Colin Custers, Paraskevi Athanasouli, Mariana Schroiff, Riet Cornelis, Jonathan Sai-Hong Chui, Richard H Finnell, Frederic Lluis, Kian Peng Koh

Faculty, Staff and Students Publications

Gastrulation begins when the epiblast forms the primitive streak or becomes definitive ectoderm. During this lineage bifurcation, the DNA dioxygenase TET1 has bipartite functions in transcriptional activation and repression, but the mechanisms remain unclear. By converting mouse embryonic stem cells (ESCs) into neuroprogenitors, we defined how Tet1-/- cells switch from neuroectoderm fate to form mesoderm and endoderm. We identified the Wnt repressor Tcf7l1 as a TET1 target that suppresses Wnt/β-catenin and Nodal signalling. ESCs expressing catalytic dead TET1 retain neural potential but activate Nodal and subsequently Wnt/β-catenin pathways to generate also mesoderm and endoderm. At CpG-poor distal enhancers, TET1 maintains …

Immune Microenvironment Remodeling After Radiation Of A Progressing Brain Metastasis, William H Hudson, Jeffrey J Olson, Lisa J Sudmeier

Faculty, Staff and Students Publications

Radiation is commonly used in the treatment of many cancers. However, its effects on anti-tumor immune responses are incompletely understood. Here, we present a detailed immunological analysis of two tumors from a patient with multiple non-small cell lung cancer metastases to the brain. One tumor was resected without treatment; the second was irradiated to a total dose of 30 Gy and resected following further progression. Comprehensive single-cell analysis reveals a substantially reduced immune cell fraction in the irradiated tumor, including the depletion of tissue-resident macrophages and infiltration of pro-inflammatory monocytes. Despite the presence of similar somatic mutations in both tumors, …

Histone H2a Lys130 Acetylation Epigenetically Regulates Androgen Production In Prostate Cancer, Thanh Nguyen, Dhivya Sridaran, Surbhi Chouhan, Cody Weimholt, Audrey Wilson, Jingqin Luo, Tiandao Li, John Koomen, Bin Fang, Nagireddy Putluri, Arun Sreekumar, Felix Y Feng, Kiran Mahajan, Nupam P Mahajan

Faculty, Staff and Students Publications

The testicular androgen biosynthesis is well understood, however, how cancer cells gauge dwindling androgen to dexterously initiate its de novo synthesis remained elusive. We uncover dual-phosphorylated form of sterol regulatory element-binding protein 1 (SREBF1), pY673/951-SREBF1 that acts as an androgen sensor, and dissociates from androgen receptor (AR) in androgen deficient environment, followed by nuclear translocation. SREBF1 recruits KAT2A/GCN5 to deposit epigenetic marks, histone H2A Lys130-acetylation (H2A-K130ac) in SREBF1, reigniting de novo lipogenesis & steroidogenesis. Androgen prevents SREBF1 nuclear translocation, promoting T cell exhaustion. Nuclear SREBF1 and H2A-K130ac levels are significantly increased and directly correlated with late-stage prostate cancer, reversal of …

Cfp1 Governs Uterine Epigenetic Landscapes To Intervene In Progesterone Responses For Uterine Physiology And Suppression Of Endometriosis, Seung Chel Yang, Mira Park, Kwon-Ho Hong, Hyeonwoo La, Chanhyeok Park, Peike Wang, Gaizhen Li, Qionghua Chen, Youngsok Choi, Francesco J Demayo, John P Lydon, David G Skalnik, Hyunjung J Lim, Seok-Ho Hong, So Hee Park, Yeon Sun Kim, Hye-Ryun Kim, Haengseok Song

Faculty, Staff and Students Publications

Progesterone (P4) is required for the preparation of the endometrium for a successful pregnancy. P4 resistance is a leading cause of the pathogenesis of endometrial disorders like endometriosis, often leading to infertility; however, the underlying epigenetic cause remains unclear. Here we demonstrate that CFP1, a regulator of H3K4me3, is required for maintaining epigenetic landscapes of P4-progesterone receptor (PGR) signaling networks in the mouse uterus. Cfp1f/f;Pgr-Cre (Cfp1d/d) mice showed impaired P4 responses, leading to complete failure of embryo implantation. mRNA and chromatin immunoprecipitation sequencing analyses showed that CFP1 regulates uterine mRNA profiles not only in H3K4me3-dependent …

Studies On The Leukocyte-Associated Ig-Like Inhibitory Receptor-1 Signaling Pathway In T Lymphocytes, Chidi Zacheaus

Theses and Dissertations (ETD)

Inflammation is a natural process in which the immune system concertedly responds to pathogens and abnormal cell growth to protect the host. For an efficient/effective immune response that circumvents tissue atrophy, a delicate balance between stimulatory and inhibitory mechanisms is essential for the proper functioning of the immune system. Immuno-receptor Tyrosine-based Inhibitory Motif (ITIM)-bearing receptors in immune cells, including T lymphocytes, play a major role in preventing autoimmune responses. Leukocyte-associated Ig-like Inhibitory Receptor 1 (LAIR-1) is one of ITIM-bearing receptors. The mechanism by which LAIR-1 attenuates T-cell response has yet to be completely understood. In this study, I investigated a …

Exome-Wide Assessment Of Isolated Biliary Atresia: A Report From The National Birth Defects Prevention Study Using Child-Parent Trios And A Case-Control Design To Identify Novel Rare Variants, Pagna Sok, Aniko Sabo, Lynn M Almli, Mary M Jenkins, Wendy N Nembhard, A J Agopian, Michael J Bamshad, Elizabeth E Blue, Lawrence C Brody, Austin L Brown, Marilyn L Browne, Mark A Canfield, Suzan L Carmichael, Jessica X Chong, Shannon Dugan-Perez, Marcia L Feldkamp, Richard H Finnell, Richard A Gibbs, Denise M Kay, Yunping Lei, Qingchang Meng, Cynthia A Moore, James C Mullikin, Donna Muzny, Andrew F Olshan, Faith Pangilinan, Jennita Reefhuis, Paul A Romitti, Jeremy M Schraw, Gary M Shaw, Martha M Werler, Sanjiv Harpavat, Philip J Lupo, University Of Washington Center For Mendelian Genomics, Nisc Comparative Sequencing Program, The National Birth Defects Prevention Study

Faculty, Staff and Students Publications

The etiology of biliary atresia (BA) is unknown, but recent studies suggest a role for rare protein-altering variants (PAVs). Exome sequencing data from the National Birth Defects Prevention Study on 54 child-parent trios, one child-mother duo, and 1513 parents of children with other birth defects were analyzed. Most (91%) cases were isolated BA. We performed (1) a trio-based analysis to identify rare de novo, homozygous, and compound heterozygous PAVs and (2) a case-control analysis using a sequence kernel-based association test to identify genes enriched with rare PAVs. While we replicated previous findings on PKD1L1, our results do not suggest that …

Long Non-Coding Rnas: Definitions, Functions, Challenges And Recommendations, John S Mattick, Paulo P Amaral, Piero Carninci, Susan Carpenter, Howard Y Chang, Ling-Ling Chen, Runsheng Chen, Caroline Dean, Marcel E Dinger, Katherine A Fitzgerald, Thomas R Gingeras, Mitchell Guttman, Tetsuro Hirose, Maite Huarte, Rory Johnson, Chandrasekhar Kanduri, Philipp Kapranov, Jeanne B Lawrence, Jeannie T Lee, Joshua T Mendell, Timothy R Mercer, Kathryn J Moore, Shinichi Nakagawa, John L Rinn, David L Spector, Igor Ulitsky, Yue Wan, Jeremy E Wilusz, Mian Wu

Faculty, Staff and Students Publications

Genes specifying long non-coding RNAs (lncRNAs) occupy a large fraction of the genomes of complex organisms. The term 'lncRNAs' encompasses RNA polymerase I (Pol I), Pol II and Pol III transcribed RNAs, and RNAs from processed introns. The various functions of lncRNAs and their many isoforms and interleaved relationships with other genes make lncRNA classification and annotation difficult. Most lncRNAs evolve more rapidly than protein-coding sequences, are cell type specific and regulate many aspects of cell differentiation and development and other physiological processes. Many lncRNAs associate with chromatin-modifying complexes, are transcribed from enhancers and nucleate phase separation of nuclear condensates …

Conjugated Bile Acids Are Nutritionally Re-Programmable Antihypertensive Metabolites, Saroj Chakraborty, Anju Lulla, Xi Cheng, Ji-Youn Yeo, Juthika Mandal, Tao Yang, Xue Mei, Piu Saha, Rachel M Golonka, Beng San Yeoh, Blair Mell, Wei Jia, Vasanta Putluri, Danthasinghe Waduge Badrajee Piyarathna, Nagireddy Putluri, Arun Sreekumar, Katie Meyer, Matam Vijay-Kumar, Bina Joe

Faculty, Staff and Students Publications

BACKGROUND: Hypertension is the largest risk factor affecting global mortality. Despite available medications, uncontrolled hypertension is on the rise, whereby there is an urgent need to develop novel and sustainable therapeutics. Because gut microbiota is now recognized as an important entity in blood pressure regulation, one such new avenue is to target the gut-liver axis wherein metabolites are transacted via host-microbiota interactions. Knowledge on which metabolites within the gut-liver axis regulate blood pressure is largely unknown.

METHOD: To address this, we analyzed bile acid profiles of human, hypertensive and germ-free rat models and report that conjugated bile acids are inversely …

Characterization Of Folic Acid, 5-Methyltetrahydrofolate And Synthetic Folinic Acid In The High-Affinity Folate Transporters: Impact On Pregnancy And Development, Ana M Palacios, Rachel A Feiner, Robert M Cabrera

Faculty, Staff and Students Publications

Folates are B vitamins that are essential for several molecular, cellular, and biological processes, including nucleotide synthesis, methylation, and methionine cycling. The physiological impacts of these processes on health also extend to cell proliferation, folate deficiency anemia, and reduction of the risk of birth defects during pregnancy. The primary objective of this study was to characterize the binding affinities of different folate forms, folic acid (FA), 5-methyltetrahydrofolate (5MTHF), and folinic acid, to the folate receptors α and β, and to the bovine milk folate binding protein. These three dietary forms of folate are found in enriched grains (FA), various fruits …

Commentary: Myocardial Relaxation Matters, Paige E Brlecic, Todd K Rosengart

Faculty, Staff and Students Publications

No abstract provided.

Gastrulation Morphogenesis In Synthetic Systems, Alyssa A Emig, Margot L K Williams

Faculty, Staff and Students Publications

Recent advances in pluripotent stem cell culture allow researchers to generate not only most embryonic cell types, but also morphologies of many embryonic structures, entirely in vitro. This recreation of embryonic form from naïve cells, known as synthetic morphogenesis, has important implications for both developmental biology and regenerative medicine. However, the capacity of stem cell-based models to recapitulate the morphogenetic cell behaviors that shape natural embryos remains unclear. In this review, we explore several examples of synthetic morphogenesis, with a focus on models of gastrulation and surrounding stages. By varying cell types, source species, and culture conditions, researchers have recreated …