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Full-Text Articles in Cell and Developmental Biology
Invited Review: Adrenocortical Function In Avian And Non-Avian Reptiles: Insights From Dispersed Adrenocortical Cells., Rocco V. Carsia, Patrick J. Mcilroy, Henry B John-Alder
Invited Review: Adrenocortical Function In Avian And Non-Avian Reptiles: Insights From Dispersed Adrenocortical Cells., Rocco V. Carsia, Patrick J. Mcilroy, Henry B John-Alder
Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship
Herein we review our work involving dispersed adrenocortical cells from several lizard species: the Eastern Fence Lizard (Sceloporus undulatus), Yarrow's Spiny Lizard (Sceloporus jarrovii), Striped Plateau Lizard (Sceloporus virgatus) and the Yucatán Banded Gecko (Coleonyx elegans). Early work demonstrated changes in steroidogenic function of adrenocortical cells derived from adult S. undulatus associated with seasonal interactions with sex. However, new information suggests that both sexes operate within the same steroidogenic budget over season. The observed sex effect was further explored in orchiectomized and ovariectomized lizards, some supported with exogenous testosterone. Overall, a suppressive effect of testosterone was evident, especially in cells …
Role Of Chronic Stress-Induced Neuroinflammation In Rodent Locus Coeruleus Physiology And Anxiety-Like Behaviors, Arthur Anthony Alfonso Reyes
Role Of Chronic Stress-Induced Neuroinflammation In Rodent Locus Coeruleus Physiology And Anxiety-Like Behaviors, Arthur Anthony Alfonso Reyes
Graduate School of Biomedical Sciences Theses and Dissertations
The locus coeruleus (LC), the primary site of brain norepinephrine (NE), is a key anatomical brain region implicated in the stress response. Stress is a neuroendocrine physiologic response to a stressor that promotes organism survival through adaptive change and restoration of homeostasis. The central stress response, which drives behavioral and physiological change, is primarily mediated by activating the hypothalamic-pituitary-adrenal (HPA) axis. While advantageous in the short term, chronic stress exposure can lead to HPA axis and LC dysregulation, which are thought to contribute to the etiology of anxiety disorders. Previous studies demonstrate the effects of acute stress in increasing LC …
Long-Term Impacts Of Acute Stressor Exposure On Locus Coeruleus Function And Anxiety-Like Behavior In Rats, Olga Borodovitsyna
Long-Term Impacts Of Acute Stressor Exposure On Locus Coeruleus Function And Anxiety-Like Behavior In Rats, Olga Borodovitsyna
Graduate School of Biomedical Sciences Theses and Dissertations
Stress is a physiological state characterized by behavioral arousal that occurs during exposure to harmful or threatening stimuli, and usually facilitates an adaptive behavioral response. The persistence of stress sometimes causes it to become maladaptive, potentially contributing to disease development, including physiological complications with altered neuroendocrine signaling and impaired function of organ systems, and psychological conditions including depression and anxiety. Anxiety disorders in particular are associated with a history of stress and are the most common class of mental disorders, with a lifetime prevalence of 33.7% in the general population. The locus coeruleus (LC) is a major node in the …
Profiling Prostate Cancer Therapeutic Resistance, Cameron A. Wade, Natasha Kyprianou
Profiling Prostate Cancer Therapeutic Resistance, Cameron A. Wade, Natasha Kyprianou
Urology Faculty Publications
The major challenge in the treatment of patients with advanced lethal prostate cancer is therapeutic resistance to androgen-deprivation therapy (ADT) and chemotherapy. Overriding this resistance requires understanding of the driving mechanisms of the tumor microenvironment, not just the androgen receptor (AR)-signaling cascade, that facilitate therapeutic resistance in order to identify new drug targets. The tumor microenvironment enables key signaling pathways promoting cancer cell survival and invasion via resistance to anoikis. In particular, the process of epithelial-mesenchymal-transition (EMT), directed by transforming growth factor-β (TGF-β), confers stem cell properties and acquisition of a migratory and invasive phenotype via resistance to anoikis. Our …
Kruppel-Like Factor 4-Dependent Staufen1-Mediated Mrna Decay Regulates Cortical Neurogenesis, Byoung-San Moon, Jinlun Bai, Mingyang Cai, Chunming Liu, Jiandang Shi, Wange Lu
Kruppel-Like Factor 4-Dependent Staufen1-Mediated Mrna Decay Regulates Cortical Neurogenesis, Byoung-San Moon, Jinlun Bai, Mingyang Cai, Chunming Liu, Jiandang Shi, Wange Lu
Molecular and Cellular Biochemistry Faculty Publications
Kruppel-like factor 4 (Klf4) is a zinc-finger-containing protein that plays a critical role in diverse cellular physiology. While most of these functions attribute to its role as a transcription factor, it is postulated that Klf4 may play a role other than transcriptional regulation. Here we demonstrate that Klf4 loss in neural progenitor cells (NPCs) leads to increased neurogenesis and reduced self-renewal in mice. In addition, Klf4 interacts with RNA-binding protein Staufen1 (Stau1) and RNA helicase Ddx5/17. They function together as a complex to maintain NPC self-renewal. We report that Klf4 promotes Stau1 recruitment to the 3′-untranslated region of neurogenesis-associated mRNAs, …
Deficiency Of Klf4 Compromises The Lung Function In An Acute Mouse Model Of Allergic Asthma, Jeanette A. Nimpong, Wintana Gebregziabher, Udai P. Singh, Prakash Nagarkatti, Mitzi Nagarkatti, Johnie Hodge, Chunming Liu, Daping Fan, Walden Ai
Deficiency Of Klf4 Compromises The Lung Function In An Acute Mouse Model Of Allergic Asthma, Jeanette A. Nimpong, Wintana Gebregziabher, Udai P. Singh, Prakash Nagarkatti, Mitzi Nagarkatti, Johnie Hodge, Chunming Liu, Daping Fan, Walden Ai
Molecular and Cellular Biochemistry Faculty Publications
Asthma is a chronic inflammatory disease of the airways and the mechanisms are not fully understood. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of monocytes, granulocyte and myeloid cells at early stage of differentiation. They possess phenotypic plasticity and regulate airway inflammation. We recently reported that Kruppel-like factor 4 (KLF4) regulates MDSC differentiation into fibrocytes, emerging effectors in chronic inflammation. However, the role of KLF4 in asthma is not known. Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine and a key initiator of allergic airway inflammation. Given the fact that TSLP promotes Th2 cytokine production that increases MDSC …
P-Rex1 Promotes Resistance To Vegf/Vegfr-Targeted Therapy In Prostate Cancer, Hira Lal Goel, Bryan Pursell, Leonard D. Shultz, Dale L. Greiner, Rolf A Brekken, Craig W. Vander Kooi, Arthur M. Mercurio
P-Rex1 Promotes Resistance To Vegf/Vegfr-Targeted Therapy In Prostate Cancer, Hira Lal Goel, Bryan Pursell, Leonard D. Shultz, Dale L. Greiner, Rolf A Brekken, Craig W. Vander Kooi, Arthur M. Mercurio
Molecular and Cellular Biochemistry Faculty Publications
Autocrine VEGF signaling is critical for sustaining prostate and other cancer stem cells (CSCs), and it is a potential therapeutic target, but we observed that CSCs isolated from prostate tumors are resistant to anti-VEGF (bevacizumab) and anti-VEGFR (sunitinib) therapy. Intriguingly, resistance is mediated by VEGF/neuropilin signaling, which is not inhibited by bevacizumab and sunitinib, and it involves the induction of P-Rex1, a Rac GEF, and consequent Rac1-mediated ERK activation. This induction of P-Rex1 is dependent on Myc. CSCs isolated from the PTENpc−/− transgenic model of prostate cancer exhibit Rac1-dependent resistance to bevacizumab. Rac1 inhibition or P-Rex1 downregulation increases the …
Nuclear Pore Component Nup98 Is A Potential Tumor Suppressor And Regulates Posttranscriptional Expression Of Select P53 Target Genes, Stephan Singer, Ruiying Zhao, Anthony M. Barsotti, Anette Ouwehand, Mina Fazollahi, Elias Coutavas, Kai Breuhahn, Olaf Neumann, Thomas Longerich, Tobias Pusterla, Maureen A. Powers, Keith M. Giles, Peter J. Leedman, Jochen Hess, David Grunwald, Harmen J. Bussemaker, Robert H. Singer, Peter Schirmacher, Carol Prives
Nuclear Pore Component Nup98 Is A Potential Tumor Suppressor And Regulates Posttranscriptional Expression Of Select P53 Target Genes, Stephan Singer, Ruiying Zhao, Anthony M. Barsotti, Anette Ouwehand, Mina Fazollahi, Elias Coutavas, Kai Breuhahn, Olaf Neumann, Thomas Longerich, Tobias Pusterla, Maureen A. Powers, Keith M. Giles, Peter J. Leedman, Jochen Hess, David Grunwald, Harmen J. Bussemaker, Robert H. Singer, Peter Schirmacher, Carol Prives
David Grünwald
The p53 tumor suppressor utilizes multiple mechanisms to selectively regulate its myriad target genes, which in turn mediate diverse cellular processes. Here, using conventional and single-molecule mRNA analyses, we demonstrate that the nucleoporin Nup98 is required for full expression of p21, a key effector of the p53 pathway, but not several other p53 target genes. Nup98 regulates p21 mRNA levels by a posttranscriptional mechanism in which a complex containing Nup98 and the p21 mRNA 3'UTR protects p21 mRNA from degradation by the exosome. An in silico approach revealed another p53 target (14-3-3sigma) to be similarly regulated by Nup98. The expression …
Large-Scale Identification Of Chemically Induced Mutations In Drosophila Melanogaster., Nele A Haelterman, Lichun Jiang, Yumei Li, Vafa Bayat, Hector Sandoval, Berrak Ugur, Kai Li Tan, Ke Zhang, Danqing Bei, Bo Xiong, Wu-Lin Charng, Theodore Busby, Adeel Jawaid, Gabriela David, Manish Jaiswal, Koen J T Venken, Shinya Yamamoto, Rui Chen, Hugo J Bellen
Large-Scale Identification Of Chemically Induced Mutations In Drosophila Melanogaster., Nele A Haelterman, Lichun Jiang, Yumei Li, Vafa Bayat, Hector Sandoval, Berrak Ugur, Kai Li Tan, Ke Zhang, Danqing Bei, Bo Xiong, Wu-Lin Charng, Theodore Busby, Adeel Jawaid, Gabriela David, Manish Jaiswal, Koen J T Venken, Shinya Yamamoto, Rui Chen, Hugo J Bellen
Faculty Publications
Forward genetic screens using chemical mutagens have been successful in defining the function of thousands of genes in eukaryotic model organisms. The main drawback of this strategy is the time-consuming identification of the molecular lesions causative of the phenotypes of interest. With whole-genome sequencing (WGS), it is now possible to sequence hundreds of strains, but determining which mutations are causative among thousands of polymorphisms remains challenging. We have sequenced 394 mutant strains, generated in a chemical mutagenesis screen, for essential genes on the Drosophila X chromosome and describe strategies to reduce the number of candidate mutations from an average of …
The Allantois And Chorion, When Isolated Before Circulation Or Chorio-Allantoic Fusion, Have Hematopoietic Potential, Brandon M. Zeigler, Daisuke Sugiyama, Michael Chen, Yalin Guo, K. M. Downs, N. A. Speck
The Allantois And Chorion, When Isolated Before Circulation Or Chorio-Allantoic Fusion, Have Hematopoietic Potential, Brandon M. Zeigler, Daisuke Sugiyama, Michael Chen, Yalin Guo, K. M. Downs, N. A. Speck
Dartmouth Scholarship
The chorio-allantoic placenta forms through the fusion of the allantois (progenitor tissue of the umbilical cord), with the chorionic plate. The murine placenta contains high levels of hematopoietic stem cells, and is therefore a stem cell niche. However, it is not known whether the placenta is a site of hematopoietic cell emergence, or whether hematopoietic cells originate from other sites in the conceptus and then colonize the placenta. Here, we show that the allantois and chorion, isolated prior to the establishment of circulation, have the potential to give rise to myeloid and definitive erythroid cells following explant culture. We further …