Digital Commons Network^™

Deparylation Is Critical For S Phase Progression And Cell Survival, Litong Nie, Chao Wang, Min Huang, Xiaoguang Liu, Xu Feng, Mengfan Tang, Siting Li, Qinglei Hang, Hongqi Teng, Xi Shen, Li Ma, Boyi Gan, Junjie Chen

Faculty, Staff and Student Publications

Poly(ADP-ribose)ylation or PARylation by PAR polymerase 1 (PARP1) and dePARylation by poly(ADP-ribose) glycohydrolase (PARG) are equally important for the dynamic regulation of DNA damage response. PARG, the most active dePARylation enzyme, is recruited to sites of DNA damage via pADPr-dependent and PCNA-dependent mechanisms. Targeting dePARylation is considered an alternative strategy to overcome PARP inhibitor resistance. However, precisely how dePARylation functions in normal unperturbed cells remains elusive. To address this challenge, we conducted multiple CRISPR screens and revealed that dePARylation of S phase pADPr by PARG is essential for cell viability. Loss of dePARylation activity initially induced S-phase-specific pADPr signaling, which …

A Compendium Of Multi-Omics Data Illuminating Host Responses To Lethal Human Virus Infections, Amie J Eisfeld, Larissa B Thackray, Qing Tan, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Human infections caused by viral pathogens trigger a complex gamut of host responses that limit disease, resolve infection, generate immunity, and contribute to severe disease or death. Here, we present experimental methods and multi-omics data capture approaches representing the global host response to infection generated from 45 individual experiments involving human viruses from the Orthomyxoviridae, Filoviridae, Flaviviridae, and Coronaviridae families. Analogous experimental designs were implemented across human or mouse host model systems, longitudinal samples were collected over defined time courses, and global multi-omics data (transcriptomics, proteomics, metabolomics, and lipidomics) were acquired by microarray, RNA sequencing, or mass spectrometry analyses. For …

Integrated Multiscale Mechano-Biological Study Of Lung And Liver Tissues, Hugh Xiao

Yale Graduate School of Arts and Sciences Dissertations

Tissues and bodily fluids undergo continuous changes as a natural life cycle process. Extracellular matrices (ECMs), which provide structural and biochemical support for the cells, and extracellular fluids (ECFs), which transport nutrients, oxygen, and waste products, exhibit several mechanical properties that can impact cell behaviors. These properties include, for example, fibrillar alignment, density, and stiffness of ECMs, and osmolarity and viscosity of ECFs. These mechano-biological cues can impact cell behaviors and change tissue landscapes. Fibrosis is known for thickened extracellular matrix, which involves many changes in mechanical properties of extracellular environment. There is much to be explored as to how …

Antioxidant Properties And Aldose Reductase Inhibitory Potency Of Viscum Album L. Extracts: Experimental And Computational Insights, Bilal Akyüz, Bülent Şengül

Turkish Journal of Agriculture and Forestry

This study systematically investigates the antioxidant capacity and inhibitory impact of Viscum album L. plant extracts on the aldose reductase (AR) enzyme through a combined approach of in vitro and in silico methods. Various sections derived from distinct plant parts were examined, revealing potent inhibitory potential. Notably, the methanol extract sourced from the plant's stem displayed remarkable efficacy with an IC50 value of 0.156 µM. Total phenolic content and antioxidant capacity analyses were conducted, highlighting variations across plant parts and solvent types. Qualitative and quantitative phenolic compounds content in the extracts was also elucidated by LC-MS/MS analysis and it was …

Effect Of Lunar Magnetic Field And Lunar Regolith Simulant On The Growth And Bioactive Compounds Production Of Chlorella Vulgaris Microalgae, Jeries Philip Butros Abedrabbo

Mechanical & Aerospace Engineering Theses & Dissertations

Since humans last went to the moon on the Apollo missions, there has been a fascination with inhabiting and colonizing other planetary objects, starting with the Earth’s Moon, Mars, and recently Jupiter’s moon, Europa. However, there is still lack of knowledge and science behind many of the extraterrestrial environmental effects on biological organisms living on Earth. Therefore, there is a need to study how such environments would affect these organisms. Moreover, how can we attain sustainable living in such environments as well through self-providing life support systems (LSS), without the need to provide for additional necessities back and forth from …

Synthesis, Characterization And Bioactivity Evaluation For Some Metal Ions Complexes With New Ligand Derived From 2-Hydroxy-1- Napthaldehyed, Andy Mohammed Abd-Alaziz, Abbas Ali Salih Al-Hamdani, Waleed Ali Mahmmoud, Zinah Hazim Abdulraheem

Baghdad Science Journal

The newly synthesized Schiff base ligand (E)-2-((2-phenylhydrazono)methyl)naphthalen-1-ol (phenyl hydrazine derivative), is allowed to react with each of the next mineral ion: Ni2+, Cu2+, Zn2+andCd2+successfully resulting to obtain new metal complexes with different geometric shape. The formation of Schiff base complexes and also the origin Schiff base is indicated using LC-Mass that manifest the obtained molar mass, FT-IR proved the occurrence of coordination through N of azobenzene and O of OH by observing the shifting in azomethines band and appearing of M-N and N-O bands. Moreover, we can also detect by such apparatus, the presence of aquatic water molecule inside the …

Fluorescence Microscopy With Deep Uv, Near Uv, And Visible Excitation For In Situ Detection Of Microorganisms, Noel Case, Nikki Johnston, Jay Nadeau

Physics Faculty Publications and Presentations

We report a simple, inexpensive design of a fluorescence microscope with light-emitting diode (LED) excitation for detection of labeled and unlabeled microorganisms in mineral substrates. The use of deep UV (DUV) excitation with visible emission requires no specialized optics or slides and can be implemented easily and inexpensively using an oblique illumination geometry. DUV excitation (<280 >nm) is preferable to near UV (365 nm) for avoidance of mineral autofluorescence. When excited with DUV, unpigmented bacteria show two emission peaks: one in the near UV ∼320 nm, corresponding to proteins, and another peak in the blue to green range, corresponding to …

Cytogenetic And Molecular Associations With Outcomes In Higher-Risk Myelodysplastic Syndromes Treated With Hypomethylating Agents Plus Venetoclax, Alexandre Bazinet, Sai Prasad Desikan, Ziyi Li, Juan Jose Rodriguez-Sevilla, Sangeetha Venugopal, Samuel Urrutia, Guillermo Montalban-Bravo, Koji Sasaki, Kelly S Chien, Danielle Hammond, Rashmi Kanagal-Shamanna, Irene Ganan-Gomez, Tapan M Kadia, Gautam Borthakur, Courtney D Dinardo, Naval G Daver, Elias J Jabbour, Farhad Ravandi, Hagop Kantarjian, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Purpose: Hypomethylating agents (HMA) combined with venetoclax are an emerging therapeutic strategy for higher-risk myelodysplastic syndromes (HR-MDS). The cytogenetic and molecular factors associated with outcomes with this combination for HR-MDS are incompletely understood.

Experimental design: We pooled patient data from 3 prospective trials evaluating HMA-venetoclax in HR-MDS to study associations between cytogenetic and molecular factors and overall response rate (ORR), overall survival (OS), and event-free survival (EFS). The Kaplan-Meier method was used to estimate time-to-event endpoints. Univariate and multivariate analyses using logistic regression (for ORR) or the Cox proportional hazards model (for OS and EFS) were used to identify associations …

The Role Of Alkbh1 In The Epigenetic Regulation Of Extraembryonic Development And Early Embryogenesis, Myles Harris Alderman Iii

Yale Graduate School of Arts and Sciences Dissertations

Successful embryogenesis requires regulated and organized stem cell differentiation from the very first cell fate decision through terminal differentiation of daughter cells within tissues. A key regulatory mechanism of stem cell differentiation and cellular identity is epigenetic regulation, whereby sequence-preserving modifications to individual bases of DNA and histone-modifications work in concert to regulate nucleosome deposition and chromatin accessibility. The past several decades of stem cell and epigenetics research have uncovered a complex regulatory environment during placental development that is not only necessary for the propagation of any mammalian species or individual, but approximates that of malignant disease. Studying the basic …

A Comprehensive Review On Solenostemma Argel (Del.) Hayne, An Egyptian Medicinal Plant, Essam Abdel-Sattar, Riham A. El-Shiekh

Bulletin of Faculty of Pharmacy Cairo University

Solenostemma argel (Del.) Hayne, commonly known as Arghel or Hargal, is a desert plant belonging to the family Apocynaceae. It has been used in traditional medicine in various countries, including Saudi Arabia, Egypt, Libya, Algeria, and Sudan, where it is the primary source. The review is aimed at providing a comprehensive report on Solenostemma argel (Del.) Hayne, including its botanical identification and description, geographical distribution, traditional uses, phytoconstituents, and pharmacological and toxicological properties. A professional search in the available literature was performed through several databases. The search was performed using the following keywords: Solenostemma argel, Argel, chemical structures, biological effects, …

The Quest For A Sensitive And Accurate Flash Radiation Model: Whole Abdominal Irradiation And Real Time Dosimetry, Noah J G Daniel

Dartmouth College Master’s Theses

Cancer remains the second leading cause of death in the US, and more than 50% of all cancer patients receive radiation therapy (RT), often in combination with surgery, chemotherapy and/or immunotherapy. However, the fundamental limit on radiotherapy treatment efficacy is normal tissue tolerance. One potential way to overcome this limitation is through ultra-high dose rate radiation (FLASH RT). Compared to conventional radiotherapy (CONV RT), FLASH RT has been shown to be just as damaging to cancerous tissue but far more sparing of healthy tissue.

However, clinical translation of FLASH research has been obstructed by the failure of many labs to …

Gut Microbiota Composition Is Associated With The Efficacy Of Delta-24-Rgdox In Malignant Gliomas, Natalie M Meléndez-Vázquez, Teresa T Nguyen, Xuejun Fan, Andrés R López-Rivas, Juan Fueyo, Candelaria Gomez-Manzano, Filipa Godoy-Vitorino

Faculty, Staff and Student Publications

Glioblastoma, the most common primary brain tumor, has a 6.8% survival rate 5 years post diagnosis. Our team developed an oncolytic adenovirus with an OX-40L expression cassette named Delta-24-RGDOX. While studies have revealed the interaction between the gut microbiota and immunotherapy agents, there are no studies linking the gut microbiota with viroimmunotherapy efficacy. We hypothesize that gut bacterial signatures will be associated with oncolytic viral therapy efficacy. To test this hypothesis, we evaluated the changes in gut microbiota in two mouse cohorts: (1) GSC-005 glioblastoma-bearing mice treated orally with indoximod, an immunotherapeutic agent, or with Delta-24-RGDOX by intratumoral injection and …

Gut Microbiota Composition Is Associated With The Efficacy Of Delta-24-Rgdox In Malignant Gliomas, Natalie M Meléndez-Vázquez, Teresa T Nguyen, Xuejun Fan, Andrés R López-Rivas, Juan Fueyo, Candelaria Gomez-Manzano, Filipa Godoy-Vitorino

Faculty, Staff and Student Publications

Glioblastoma, the most common primary brain tumor, has a 6.8% survival rate 5 years post diagnosis. Our team developed an oncolytic adenovirus with an OX-40L expression cassette named Delta-24-RGDOX. While studies have revealed the interaction between the gut microbiota and immunotherapy agents, there are no studies linking the gut microbiota with viroimmunotherapy efficacy. We hypothesize that gut bacterial signatures will be associated with oncolytic viral therapy efficacy. To test this hypothesis, we evaluated the changes in gut microbiota in two mouse cohorts: (1) GSC-005 glioblastoma-bearing mice treated orally with indoximod, an immunotherapeutic agent, or with Delta-24-RGDOX by intratumoral injection and …

Controlled Release Of Radioactive Water From The Fukushima Daiichi Nuclear Power Plant: Should We Be Concerned?, Maria F. Ferreira, Andrew Turner, Awadhesh N. Jha

School of Biological and Marine Sciences

Following the Fukushima Daiichi nuclear disaster in 2011, the decision to release more than 1 million tons of radioactive water into the ocean by the Japanese government, with approval from the IAEA, has divided public and scientific opinion. The discharge began on August 24, 2023, with the premise that, after removal of long-lived radionuclides (i.e., 137Cs and 90Sr), tritium (3H), the primary remaining radionuclide as tritiated water (HTO), will be sufficiently and safely diluted over a 30-year period. (1) Concerns, however, relate to (a) the safety of seafood and its consumers and (b) potential long-term consequences on human and environmental …

Bioaccumulation Influences Of Some Heavy Metals On Growth Performance Of Solea Solea Fish In Lake Qaroun, Egypt, Tarek M. Hamad, Khalid H. Zaghloul, Ahmed E. Alprol

Blue Economy

The present research examined the levels of lead, cadmium, copper and zinc in water, sediments, and some vital organs of Solea solea fish from Lake Qaroun, Egypt, such as liver, gills, kidney, muscle and end of the alimentary. The contamination factor (CF) values of Pb, Cd, Cu, and Zn are low contamination which CF ˂ 1. According to the results, fish hunted from the eastern and southeast areas of the lake had the highest concentrations of the various heavy metals in the following order: The current findings make it evident that zinc accumulated in the studied organs in the following …

The History Of -Eer In English: Suffix Competition Or Symbiosis?, Zachary Dukic, Chris C. Palmer

Faculty Articles

Ecological models of competition have provided great explanatory power regarding synonymy in derivational morphology. Competition models of this type have certainly shown their utility, as they have demonstrated, among other things, the relevance of frequency measures, productivity, compositionality and analyzability when comparing the development of morphological constructions. There has been less consideration of alternative models that could be used to describe the historical co-development of suffixes that produce words with sometimes similar forms or meanings but are not inevitably or solely in competition. The symbiotic model proposed in this article may help answer larger questions in linguistics, such as how …

Label-Aware Distance Mitigates Temporal And Spatial Variability For Clustering And Visualization Of Single-Cell Gene Expression Data, Shaoheng Liang, Jinzhuang Dou, Ramiz Iqbal, Ken Chen

Faculty, Staff and Student Publications

Clustering and visualization are essential parts of single-cell gene expression data analysis. The Euclidean distance used in most distance-based methods is not optimal. The batch effect, i.e., the variability among samples gathered from different times, tissues, and patients, introduces large between-group distance and obscures the true identities of cells. To solve this problem, we introduce Label-Aware Distance (LAD), a metric using temporal/spatial locality of the batch effect to control for such factors. We validate LAD on simulated data as well as apply it to a mouse retina development dataset and a lung dataset. We also found the utility of our …

Dysregulated Creb3 Cleavage At The Nuclear Membrane Induces Karyoptosis-Mediated Cell Death, Ga-Eun Lee, Geul Bang, Jiin Byun, Cheol-Jung Lee, Weidong Chen, Dohyun Jeung, Hyun-Jung An, Han Chang Kang, Dae Joon Kim, Megan Keniry

School of Medicine Publications

Cancer cells often exhibit resistance to apoptotic cell death, but they may be vulnerable to other types of cell death. Elucidating additional mechanisms that govern cancer cell death is crucial for developing new therapies. Our research identified cyclic AMP-responsive element-binding protein 3 (CREB3) as a crucial regulator and initiator of a unique cell death mechanism known as karyoptosis. This process is characterized by nuclear shrinkage, deformation, and the loss of nuclear components following nuclear membrane rupture. We found that the N-terminal domain (aa 1-230) of full-length CREB3 (CREB3-FL), which is anchored to the nuclear inner membrane (INM), interacts with lamins …

Phytochemical Analysis, Antioxidant Activity, And Cytotoxic Effects Of Physalis Angulata And Moringa Oleifera Leaf Extracts On Cancer And Normal Cells In Vitro, Didik Priyandoko, Wahyu Widowati, Ika Adhani Sholihah, Nurul Zahra Zahira, Adityana Arta Bangun, Kusdianti Kusdianti, Hernawati Hernawati, Wahyu Surakusumah, Rahadian Deden Juansah

Makara Journal of Science

Physalis angulata and Moringa oleifera have long been the key ingredients of traditional medicine. This study aimed to obtain the metabolite profiles of the ethanolic leaf extracts of P. angulata (ELP) and M. oleifera (ELM), evaluate their antioxidant activity, and assess their toxicity against normal and cancer cells. The leaves were sourced from Balittro, West Java. The extraction used 70% ethanol and continued for 3 days. The metabolites were identified using Gas Chromatography-Mass Spectrometry (GC-MS), antioxidant activity was ascertained via the DPPH assay, and cytotoxicity was evaluated employing the PrestoBlue assay. GC-MS identified 23 compounds in ELP and 15 in …

Seagrass-Roots Environmentalism: The Lee County Conservation Association, Chris Wilhelm

Florida Historical Quarterly

After World War II, Florida crafted a new identity: the Sunshine State. This concept was not solely based on Florida's hot weather and sunny skies although the relationship between sun and water was implicit in the new identity. Tourists enjoyed the sun on boats and beaches, retirees and snowbirds fled northern winters for new sunny coastal cities. The heat of Florida's sunshine was thus balanced by the state's coastal waters. The Sunshine State is a convenient slogan, but Florida is actually defined by its coast. Other states have more sunshine, but none in the continental U.S. have more coastline or …

Chimeric Oncolytic Adenovirus Evades Neutralizing Antibodies From Human Patients And Exhibits Enhanced Anti-Glioma Efficacy In Immunized Mice, Dong Ho Shin, Hong Jiang, Andrew G Gillard, Debora Kim, Xuejun Fan, Sanjay K Singh, Teresa T Nguyen, Sagar S Sohoni, Andres R Lopez-Rivas, Akhila Parthasarathy, Chibawanye I Ene, Joy Gumin, Frederick F Lang, Marta M Alonso, Candelaria Gomez-Manzano, Juan Fueyo

Faculty, Staff and Student Publications

Oncolytic viruses are a promising treatment for patients with high-grade gliomas, but neutralizing antibodies can limit their efficacy in patients with prior virus exposure or upon repeated virus injections. Data from a previous clinical trial using the oncolytic adenovirus Delta-24-RGD showed that generation of anti-viral neutralizing antibodies may affect the long-term survival of glioma patients. Past studies have examined the effects of neutralizing antibodies during systemic virus injections, but largely overlooked their impact during local virus injections into the brain. We found that immunoglobulins colocalized with viral proteins upon local oncolytic virotherapy of brain tumors, warranting a strategy to prevent …

Selective Targeting Of Microglia By Quantum Dots And Green Synthesis Of Metal Organic Biohybrids; Applications In Dynamic Cell And Assay Systems, Navya Uppu

Doctoral Dissertations

Neurological disorders are the leading cause of physical and cognitive disability across the globe, currently affecting approximately 15% of the worldwide population. Part of the glioma microenvironment are microglia, resident immune cells of the CNS that were thought to be involved in the pathogenesis of diverse neurodegenerative diseases. Though it remains uncertain what triggers microglial activation in these disorders, targeting and tracking microglial functions using nanotools like Quantum Dots (QDs) could help us elucidate them in such neurological diseases. This research focuses on the comparative study of different QDs formulations and their selective uptake by brain microglia in primary cultures …

A Phase 1 Trial Utilizing A Pharmacokinetic Endpoint To Determine The Optimal Dose Of Ramucirumab In Children And Adolescents With Relapsed Or Refractory Solid Tumors, Including Central Nervous System Tumors, Kristy L Pilbeam, Kamnesh Pradhan, James Croop, Charles G Minard, Xiaowei Liu, Stephan D Voss, Emasenyie Isikwei, Stacey L Berg, Joel M Reid, Elizabeth Fox, Brenda J Weigel

Center for Medical Ethics and Health Policy Staff Publications

Background: Ramucirumab is a monoclonal antibody that binds the extracellular domain of vascular endothelial growth factor receptor (VEGFR-2) and prevents binding of VEGF ligands. Based on population pharmacokinetic (PK) analysis and correlation with efficacy in adults, a target steady state trough concentration (Css,min ) ≥ 50 µg/mL was established.

Procedures: This phase 1 trial (ADVL1416) used a rolling six design and a PK primary endpoint to define the recommended phase 2 dose (RP2D) of ramucirumab in children with recurrent/refractory solid tumors. Two dose levels (DL) were planned (DL1: 8 mg/kg, DL2: 12 mg/kg administered intravenously [IV] every 2 weeks). Toxicity …

Advances In Immunocompetent Mouse And Rat Models, Wen Bu, Yi Li

Center on Aging Staff Publications

Rodent models of breast cancer have played critical roles in our understanding of breast cancer development and progression as well as preclinical testing of cancer prevention and therapeutics. In this article, we first review the values and challenges of conventional genetically engineered mouse (GEM) models and newer iterations of these models, especially those with inducible or conditional regulation of oncogenes and tumor suppressors. Then, we discuss nongermline (somatic) GEM models of breast cancer with temporospatial control, made possible by intraductal injection of viral vectors to deliver oncogenes or to manipulate the genome of mammary epithelial cells. Next, we introduce the …

Androgen Drives Melanoma Invasiveness And Metastatic Spread By Inducing Tumorigenic Fucosylation, Qian Liu

USF Tampa Graduate Theses and Dissertations

Melanoma incidence and mortality rates are historically higher for men than women, with an estimated ~47% more new cases and twice the lethality in men in the US in 2023. Consistent with these discrepancies, emerging studies have highlighted the tumorigenic role of the male sex hormone androgen and its receptor (AR) in promoting melanoma aggressiveness. However, underlying cellular and molecular mechanisms and their precise pathological contributions are not well-defined. We recently discovered a sex-associated disparity in melanoma fucosylation, the post-translational modification of proteins with the dietary sugar L-fucose. Fucosylation, the conjugation of fucose moieties onto different glycan linkages on target …

More Than Ethics: Changing Approaches To Research In Human Biology, Agustín Fuentes

Human Biology Open Access Pre-Prints

Work in biological anthropology and human biology that engages with, extracts, manipulates, analyzes and disseminates biological data from and associated with people requires serious ethical investment as central to method, theory, and practice. However, ethics is not enough. Moving beyond a call for better (or more) ethics there is a core need for anthropological, historical, anti-racist/anti-colonialist method and theory in dealing with human data (existing, newly collected, and future collections). But there are structures in the academy, historical, financial, hierarchical, discriminatory, that impede sincere and effective actions to make such changes. Encouragingly, calls for structural change, and some actions entailing …

Pulmonary Fibrosis Stakeholder Summit: A Joint Nhlbi, Three Lakes Foundation, And Pulmonary Fibrosis Foundation Workshop Report, Sydney B Montesi, Christian R Gomez, Michael Beers, Robert Brown, Ishanu Chattopadhyay, Kevin R Flaherty, Christine Kim Garcia, Brigitte Gomperts, Lida P Hariri, Cory M Hogaboam, R Gisli Jenkins, Naftali Kaminski, Grace Hyun J Kim, Melanie Königshoff, Martin Kolb, Darrell N Kotton, Jonathan A Kropski, Joseph Lasky, Chelsea M Magin, Toby M Maher, Mark Mccormick, Bethany B Moore, Cheryl Nickerson-Nutter, Justin Oldham, Anna J Podolanczuk, Ganesh Raghu, Ivan Rosas, Steven M Rowe, William T Schmidt, David Schwartz, Jessica E Shore, Cathie Spino, J Matthew Craig, Fernando J Martinez

Faculty, Staff and Students Publications

Despite progress in elucidation of disease mechanisms, identification of risk factors, biomarker discovery, and the approval of two medications to slow lung function decline in idiopathic pulmonary fibrosis and one medication to slow lung function decline in progressive pulmonary fibrosis, pulmonary fibrosis remains a disease with a high morbidity and mortality. In recognition of the need to catalyze ongoing advances and collaboration in the field of pulmonary fibrosis, the NHLBI, the Three Lakes Foundation, and the Pulmonary Fibrosis Foundation hosted the Pulmonary Fibrosis Stakeholder Summit on November 8–9, 2022. This workshop was held virtually and was organized into three topic …

Pluripotency Of A Founding Field: Rebranding Developmental Biology, Crystal D. Rogers, Chris Amemiya, Swathi Arur, Leslie Babonis, Michael Barresi, Madelaine Bartlett, Richard Behringer, Blair Benham-Pyle, Dominique Bergmann, Ben Blackman, C. Titus Brown, Bill Browne, Jasmin Camacho, Chiswili Y. Chabu, Ida Chow, Ondine Cleaver, Jonah Cool, Megan Y. Dennis, Alexandra J. Dickinson, Stefano Di Talia, Margaret Frank

Pacific Faculty Work

The field of developmental biology has declined in prominence in recent decades, with off-shoots from the field becoming more fashionable and highly funded. This has created inequity in discovery and opportunity, partly due to the perception that the field is antiquated or not cutting edge. A 'think tank' of scientists from multiple developmental biology-related disciplines came together to define specific challenges in the field that may have inhibited innovation, and to provide tangible solutions to some of the issues facing developmental biology. The community suggestions include a call to the community to help 'rebrand' the field, alongside proposals for additional …

Molecular-Guided Therapy For The Treatment Of Patients With Relapsed And Refractory Childhood Cancers: A Beat Childhood Cancer Research Consortium Trial., Giselle L Saulnier Sholler, Genevieve Bergendahl, Elizabeth C. Lewis, Jacqueline Kraveka, William Ferguson, Abhinav B. Nagulapally, Karl Dykema, Valerie I Brown, Michael S. Isakoff, Joseph Junewick, Deanna Mitchell, Jawhar Rawwas, William Roberts, Don Eslin, Javier Oesterheld, Randal K. Wada, Devang Pastakia, Virginia Harrod, Kevin Ginn, Raya Saab, Kevin Bielamowicz, Jason Glover, Eugenia Chang, Gina K. Hanna, Daniel Enriquez, Tyler Izatt, Rebecca F Halperin, Abigail Moore, Sara A. Byron, William P D Hendricks, Jeffrey M. Trent

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Children with relapsed central nervous system (CNS tumors), neuroblastoma, sarcomas, and other rare solid tumors face poor outcomes. This prospective clinical trial examined the feasibility of combining genomic and transcriptomic profiling of tumor samples with a molecular tumor board (MTB) approach to make real‑time treatment decisions for children with relapsed/refractory solid tumors.

METHODS: Subjects were divided into three strata: stratum 1-relapsed/refractory neuroblastoma; stratum 2-relapsed/refractory CNS tumors; and stratum 3-relapsed/refractory rare solid tumors. Tumor samples were sent for tumor/normal whole-exome (WES) and tumor whole-transcriptome (WTS) sequencing, and the genomic data were used in a multi-institutional MTB to make real‑time treatment …

Androgen Drives Melanoma Invasiveness And Metastatic Spread By Inducing Tumorigenic Fucosylation, Qian Liu, Emma Adhikari, Daniel K Lester, Bin Fang, Joseph O Johnson, Yijun Tian, Andrea T Mockabee-Macias, Victoria Izumi, Kelly M Guzman, Michael G White, John M Koomen, Jennifer A Wargo, Jane L Messina, Jianfei Qi, Eric K Lau

Faculty, Staff and Student Publications

Melanoma incidence and mortality rates are historically higher for men than women. Although emerging studies have highlighted tumorigenic roles for the male sex hormone androgen and its receptor (AR) in melanoma, cellular and molecular mechanisms underlying these sex-associated discrepancies are poorly defined. Here, we delineate a previously undisclosed mechanism by which androgen-activated AR transcriptionally upregulates fucosyltransferase 4 (FUT4) expression, which drives melanoma invasiveness by interfering with adherens junctions (AJs). Global phosphoproteomic and fucoproteomic profiling, coupled with in vitro and in vivo functional validation, further reveal that AR-induced FUT4 fucosylates L1 cell adhesion molecule (L1CAM), which is required for FUT4-increased metastatic …