2008 — 2012 |
Xu, Wei |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Transcriptional Regulation of Estrogen Receptor (Er) by Carm1 @ University of Wisconsin-Madison
DESCRIPTION (provided by applicant): CARM1, coactivator associated arginine (R) methyltransferase 1, is involved in the activation of a number of transcriptional factors, including NF-?B, p53, E2F1 and steroid receptors, among which transcriptional activation of estrogen receptors (ERs) by CARM1 is best characterized. CARM1 methylates histone H3 at R17, and this methylation correlates with activation of the ER-target gene pS2. Loss of CARM1 leads to abrogation of the estrogen response and reduction in expression of some ER-target genes. We recently identified a CARM1-associated complex, nucleosomal methylation activator complex (NuMAC), which includes multiple components of SWI/SNF chromatin remodeling complex. SWI/SNF has also been implicated in ER-mediated transcriptional activation, and loss of SWI/SNF function is common in cancer progression. Interestingly, we have recently found that CARM1 can be phosphorylated in vivo and that its phosphorylation inhibits its histone methyltransferase (HMT) activity. We have generated phosphorylation-defective mutants of CARM1, which provide us a powerful tool to investigate the molecular mechanism of the regulation of ER-signaling by the CARM1 complex. This study is proposed to further understand the mode of transcriptional regulation and the cellular signaling of CARM1 in the context of ER. Given the surge of interest in histone arginine methylation in transcriptional regulation and the incorporation of two enzymatic activities, HMT and ATP-dependent remodeling, in the ER coactivator complex, our long-term objectives are to analyze the molecular underpinnings of ER transcriptional regulation by the CARM1 complex and to determine its functional relevance to the development of breast cancer. Our central hypothesis is that CARM1 and its associated enzymatic activities are important in regulating a subset of ER-target genes. CARM1 plays a central role in signal transduction, which is regulated by upstream cellular pathways and encodes a methyl-mark on histones to lead to the downstream transcription activation. Here I outline a series of experiments using biochemical, cell-based, and genomic approaches to study: (a) the molecular mechanism of the regulation of ER-target gene expression by CARM1 and SWI/SNF; (b) the effect of CARM1 phosphorylation on ER-dependent transcription and upstream signaling pathways and that lead to CARM1 inactivation; and (c) the downstream cellular effects of estrogen-dependent histone arginine methylation. These studies will provide a new understanding of the mechanism and functional significance of histone arginine methylation in ER-regulated processes.
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0.958 |
2009 — 2010 |
Xu, Wei |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Identification of Eralpha/Erbeta Heterodimer-Specific Ligands by Hts @ University of Wisconsin-Madison
DESCRIPTION (provided by applicant): One out of every eight women in the United States will develop breast cancer during her lifetime. The biological actions of estrogens are transduced by its binding to two estrogen receptors (ERs), ER? and ER?, which have a "Ying and Yang" relationship in regulating estrogen action (i.e., ER? promotes while ER? inhibits estrogen-dependent cell growth). ER? is thought to counteract the stimulatory effects of ER? through heterodimerization of the two receptors, and these heterodimers have been proposed to regulate sets of genes distinct from those regulated by either homodimer. However, the mechanism by which ER? functions in concert with ER? as a heterodimer in breast cancer has not been studied in detail due to the lack of specific ER?/??heterodimer ligands. We have established highly robust and reproducible Bioluminescent Resonance Energy Transfer (BRET) assays which can distinguish ligands with ability to induce ER? homodimers, ER? homodimers and ER?/? heterodimers. This proposal outlines three specific aims that focus on high throughput screening (HTS) for identification of ER?/??heterodimer specific ligands. In Aim 1, we take advantage of an ERE-reporter stably integrated cell line that is amenable to HTS. This T47D-KBLuc cell line expresses both ER? and ER?, making it feasible to identify compounds transactivating all forms of ER dimers including ER? and ER? homodimers as well as ER?/??heterodimers. In Aim 2, estrogenic compounds identified from this primary screening will be subjected to the HTS using BRET. In Aim 3, the identified hits will be tested for their abilities to inhibit growth of breast cancer cells co- expressing ER? and ER?. Development of a novel system by which ER?/? heterodimers may be studied will provide a means for direct evidence for heterodimer formation in vivo. Furthermore, these tools will allow preliminary exploration of heterodimer function in breast cancer via cell-based assays. PUBLIC HEALTH RELEVANCE: Estrogen receptors (ERs) play essential function in regulating cell proliferation in breast cancer cells;however the biological functions of ER?/ER? heterodimer remain unknown due to lack of heterodimer-selective compound. Here we propose two-step high throughput screenings for identification of ER?/ER? heterodimer specific ligands.
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0.958 |
2013 — 2017 |
Xu, Wei |
K99Activity Code Description: To support the initial phase of a Career/Research Transition award program that provides 1-2 years of mentored support for highly motivated, advanced postdoctoral research scientists. R00Activity Code Description: To support the second phase of a Career/Research Transition award program that provides 1 -3 years of independent research support (R00) contingent on securing an independent research position. Award recipients will be expected to compete successfully for independent R01 support from the NIH during the R00 research transition award period. |
Neuronal Mechanisms For Fear Memory Generalization in Ptsd and Anxiety Disorders @ Ut Southwestern Medical Center
Project Summary: Post-traumatic stress disorder (PTSD) and some other anxiety disorders manifest as overgeneralization of fear memories that are derived from traumatic experiences but now applied to nonhazardous situations. The neuronal mechanisms determining the degree of memory precision versus generalization are largely unknown, and this lack of understanding impedes the development of effective therapies. Previously, I observed over- generalized contextual fear memory following functional manipulations of the medial prefrontal cortex or the hippocampus. Moreover, I discovered that nucleus reuniens of the midline thalamus which anatomically connects the prefrontal cortex to the hippocampus also plays an essential role. Selective inactivation of prefrontal neurons projecting to nucleus reuniens or direct inactivation of neurons in nucleus reuniens produced overgeneralization, while increasing neuronal activity in nucleus reuniens reduced fear generalization. These observations lead to my hypothesis that in the brain there is a tuning system bi-directionally adjusting the generalization level of fear memories, and this system is composed of the circuits between the prefrontal cortex, nucleus reuniens and the hippocampus. Low activity of the prefrontal cortex and nucleus reuniens decreases hippocampal representation of the details associated with a particular fear memory and leads to overgeneralization as seen in PTSD and anxiety; while increasing the activity level of the prefrontal cortex and nucleus reuniens will downregulate fear generalization level and provides therapeutic benefits. In the mentored phase of this proposal, I will systematically examine the roles of these three brain structures in determining fear generalization level and the functional relationship between these brain structures in encoding or retrieval of fear memories. Because my preliminary data indicate that a subset rather than the whole prefrontal neuronal population contributes to fear generalization, I will identify the particular prefrontal subpopulations of neurons which are specifically involved in the regulation of fear generalization and reveal their genetic identities with high throughput RNA sequencing techniques. Based on the above information, in the independent phase I will then perform detailed functional characterization of the specific prefrontal neuronal groups including their anatomical connections, electrophysiological properties and gene expression profiles. I will test if changes in these properties result in fear memory overgeneralization and anxiety. Successful completion of the proposed studies will offer a mechanistic account of a profound cognitive function - the determination of memory precision/generalization - and thus open up novel avenues for effective therapies to abate anxiety. Careerwise, I am interested in neuroscience research in an academic institute with a long-term goal to uncover the neuronal mechanisms underlying basic cognitive functions and to utilize the information thus obtained to treat brain disorders. I will primarily focus on but not limit my topics to various aspects of memory functions. To date, great strides have been made in neuroscience in the fields of cellular and molecular neurobiology as well as in human cognitive neuroscience; however, research bridging these two ends is lagging behind. I believe that detailed functional dissection of the neuronal circuits responsible for cognitive functions is pivotal to neuroscience now. Therefore, my immediate objective for the next 5-10 years will be to characterize in detail the connectivity and functional properties of the prefrontal cortex-thalamus pathways and to elucidate their roles in various cognitive functions such as those proposed here. I was initially trained in clinical medicine and then received scientific training in neuroscience. I have had extensive experience in both molecular and cellular neurobiology approaches and systems neuroscience techniques, which make me ideal for the proposed studies. The first phase of the current proposal will be conducted with mentoring from Dr. Thomas Sudhof and Dr. Ian Gotlib at Stanford University. Dr. Sudhof is a leading neurobiologist in studying synaptic functions and related mental disorders; Dr. Gotlib, a world renowned cognitive scientist with expertise in anxiety and depression research. With their guidance, my proposed studies shall be ensured in both scientific value and technical soundness. Stanford University has been the cradle of fundamental neuroscience findings and innovative neuroscience approaches and will furnish the best environment for the studies.
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0.954 |
2014 |
Alexander, Caroline Margaret Xu, Wei |
S10Activity Code Description: To make available to institutions with a high concentration of NIH extramural research awards, research instruments which will be used on a shared basis. |
Seahorse Xf96e Metabolic Analyzer Purchase @ University of Wisconsin-Madison
DESCRIPTION (provided by applicant): This proposal requests funds for a Seahorse XF96e Metabolic Analyzer. The system will be housed in the Small Molecules Screening and Synthesis Facility at the Wisconsin Institutes for Medical Research in the University of Wisconsin Carbone Cancer Center (UWCCC). It will be available for members of the UWCCC, and more widely, for researchers in the UW Hospital and Pharmacy buildings. Although there have been some 600 Analyzers sold nation-wide to date, this will be the first analyzer to come to the University of Wisconsin School of Medicine and Public Health campus. It represents a unique instrument with the potential to complement or replace the assays that are currently run in our biomedical research labs. This analyzer generates detailed information about the relative rates of glycolysis and oxidative phosphorylation, either at equilibrium, or after perturbation of live cell systems. With the re-emergence of metabolism as a key regulator of growth, not only of tumors, but stem cell populations, this instrument will be key to the interpretation of their phenotypes.
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0.958 |
2016 — 2017 |
Gong, Shaoqin Xu, Wei |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Targeting Triple Negative Breast Cancer Using Nanoparticles Loaded With the Anti-Cancer Drug Aminoflavone @ University of Wisconsin-Madison
? DESCRIPTION (provided by applicant): Breast cancer continues to be a devastating disease in spite of targeted therapies against the estrogen receptor alpha (ER?), the progesterone receptor, and the human epidermal growth factor receptor-2 (Her2). Breast cancers lacking expression of all three receptors are named triple-negative breast cancer (TNBCs). TNBCs are hard to treat due to lack of targeted therapy. Over half of TNBCs overexpress EGFR. Recently our lab showed a NCI investigational drug aminoflavone (AF) exhibits strong cytotoxicity in TNBC cells with GC50 at nM range. AF induces DNA damage, cell cycle arrest and apoptosis in TNBC cell lines. Despite promising growth inhibitory effects, several human clinical trials on AF had been terminated due to systematic toxicity. Thus, there is a pressing need to develop multifunctional nanocarriers to encapsulate AF for targeted cancer therapy. In collaboration with Dr. Gong's group, we have recently designed a unique unimolecular micelle nanoparticle platform as AF nanocarrier for targeted TNBC therapy. We have promising preliminary data indicating that conjugation of an EGFR targeting peptide, GE11, to unimolecular micelles enhances the cellular uptake of the AF-loaded nanoparticles in EGFR-overexpressing TNBC cells. This application will further examine the specificity and efficacy of AF-loaded, GE11-conjugated unimolecular micelles in in vitro and in vivo models. The grant proposal includes two specific aims: Aim 1 will test the specificity of AF-loaded, GE11-conjugated unimolecular micelles towards EGFR overexpressing vs. non-expressing triple negative breast cancer cells. Aim 2 will determine the therapeutic efficacy and systemic toxicity of AF-loaded unimolecular micelles in various in vivo models. Collectively, our study will determine whether unimolecular micelles conjugated with an EGFR-recognizing peptide, i.e. GE11, allows for targeted delivery of AF to EGFR- overexpressing TNBC, minimizing systemic toxicity while improving therapeutic efficacy.
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0.958 |
2017 — 2021 |
Xu, Wei |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Protein Arginine Methylation in Chemotherapy Resistance @ University of Wisconsin-Madison
PROJECT SUMMARY Chemotherapy continues to be an important component of therapy for breast cancer, given to reduce the risk of metastatic recurrence. Although response (sensitivity) or lack of response (resistance) to chemotherapy is associated with prognosis, there is currently no validated commercial assay available which specifically predicts response to chemotherapy. Personalized approaches to cancer therapy are needed to select a drug or combination of drugs to which a tumor is most sensitive, and to avoid the toxicity of drugs to which the tumor is or becomes resistant. Such biomarker will assist oncologists in the daily clinical management of aging patients who are fragile to multiple chemotherapies and triple negative breast cancer patients whose major treatment option is chemotherapy. Coactivator associated arginine methyltransferase 1 (CARM1) is a protein arginine (R) methyltransferase which can methylate histone H3 and a variety of non-histone substrates. We recently identified a mediator of RNA polymerase II transcription subunit 12 (MED12) as a novel substrate for CARM1. The proposed project will determine whether methylation of MED12 is a predictor for chemo-sensitivity in breast cancer. We have mapped the methylation sites of MED12 to R1862 and R1912. Coincidently, mutations on R1862 had been reported in lung and cervical cancers, and mutations on R1912 had been found in a melanoma patient who developed resistance to BRAF inhibitor. We found that overexpression of MED12 wild-type, but not MED12R1862K,R1912K mutant, increased sensitivity of HEK293 cells to 5-FU and anthracyclines. Interestingly, the MED12 methylation dependent mechanism is distinct from activation of TGF-?R signaling as reported for complete knockout of MED12 in lung and colon cancers. Further, we have identified targets regulated by methylated MED12 that may determine chemo-sensitivity. We hypothesize that methylation of MED12 by CARM1 represents an important mechanism conferring chemosensitivity. The proposed research will directly address (1) whether MED12 methylation predicts sensitivity of breast cancer cells to commonly used chemotherapies in cell culture and xenograft tumor models; (2) define the mechanism of methylated-MED12 controlled chemosensitivity; and (3) test the clinical relevance of the MED12 methylation in chemo- resistance using large cohorts of clinical specimens. The goal is to delineate the methylation dependent mechanism for chemotherapy resistance and uncover new targets for therapeutic intervention.
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0.958 |
2018 — 2021 |
Xu, Wei |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Automatic Text-Simplification and Reading-Assistance to Support Self-Directed Learning by Deaf and Hard-of-Hearing Computing Workers
While there is a shortage of computing and IT professionals in the U.S., there is underrepresentation of people who are Deaf and Hard of Hearing (DHH) in such careers. There is great diversity in the English reading skills among DHH Americans, who face challenges in the IT industry where regular upskilling is required throughout the working career. This interdisciplinary research will focus on studying automatic text-simplification technologies as reading assistance to help DHH individuals keep up with rapidly changing technologies through self-directed learning, outside of a formal classroom setting. The research team consists of experts in natural language processing (NLP), human-computer interaction (HCI), accessibility, and Deaf STEM education research. The resources and technologies developed for this project will be adaptable to other languages and text domains (e.g. medical information for lay readers), benefiting a wide range of populations (e.g. children, non-native speakers, people with reading disabilities).
Prior text-simplification research for specific user groups focused on preliminary data collection or classical NLP methods, and little HCI research has explored design options for reading-assistance systems. This project will fill this critical gap in research and will investigate the learning and reading-assistance needs of upskilling DHH computing workers, design parameters influencing usability of reading-assistance tools, new training data and methods for text simplification tailored to specific reader groups and technical genres, automatic and human-based evaluation methods, and the impact of such tools on heutagogical learning. The methods will include interview and survey research with DHH computing workers, prototyping and testing of design variations, creation of parallel simplification corpora, readability annotation of lexicon and texts by DHH individuals, NLP research on domain adaptation and syntax-based neural machine translation for text simplification, and observation of real-world deployment of a prototype with DHH students and recent graduates from computing-related programs at the National Technical Institute for the Deaf (NTID).
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
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0.948 |
2019 — 2023 |
Xu, Wei |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative: Infews: U.S.-China: Synergistic Effects of Petroleum Production and Ocean Environmental Changes On Oyster Health @ Texas a&M University Corpus Christi
This project was awarded through the "National Science Foundation (NSF) / National Natural Science Foundation of China (NSFC) Joint Research on Environmental Sustainability Challenges" opportunity. Understanding the connections between interrelated food, energy, and water (FEW) systems is essential for the development of sustainable worldwide seafood production. Fish and shellfish serve as an important source of high-quality protein and non-saturated fat. Near-shore aquaculture supplies over 50% of global seafood production. However, over the past decades, seafood species and the production of these species have been severely affected by water contamination as a result of energy production and climate change. In this study, investigators from Texas A&M University-Corpus Christi, Louisiana State University, and Dalian Ocean University in China will identify potential risks of oyster production systems exposed to the contamination of petroleum products and the adverse environmental factors of UV radiation, ocean salinity fluctuation, and ocean acidification. An ocean model containing simulated environmental stresses will be developed to predict how petroleum products impact the development and growth of oysters in near-shore habitats in the Gulf of Mexico (GoM) and in Bohai Bay (BhB), China. Data generated from this investigation could support the Food Safety Modernization Act goals of risk-ranking consumable seafood.
This study aims to address the two themes proposed in the National Science Foundation/National Natural Science Foundation of China Joint Research on Environmental Sustainability Challenges; 1) quantitative and computational modeling of a FEW system and 2) innovative human and technological solutions to critical FEW systems problems. The project uses the oyster as a model aquaculture species to assess the toxicity changes of crude oil compounds in response to environmental stresses. With the increasing activities in the petroleum industry along coastal lines, the accumulation of oil pollutants in oysters becomes a concern for human health. The locations to be studied in this project, the GoM in the US and the BhB in China, share the common characteristics of robust seafood harvesting in conjunction with a vigorous petroleum production industry. However, these marine environments have distinct differences due to their geographic locations. Hence, the two unique systems represent diversified FEW networks. This diversity of the networks is expected to be explored by the computational modeling approach developed in this study. The strategies and methods employed can be further extended to other marine aquaculture species. Moreover, this investigation on the marine impact of crude oil can translate to other marine contaminants such as pesticides and pharmaceutical products, which have also become of concern in onshore/offshore aquaculture. Research results will provide 1) a better understanding of the toxicological alterations of petroleum products under global environmental change; 2) the impacts of the modification in petroleum products on the health of aquaculture species; 3) identification of environmental stress modified petrogenic products and their toxicities to oysters that should serve as references for the management of onshore/offshore aquaculture and oil production; and 4) prediction of impacts of oil production on global ocean environments and world aquaculture concurrent with climate change.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
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0.942 |
2019 |
Xu, Wei |
R15Activity Code Description: Supports small-scale research projects at educational institutions that provide baccalaureate or advanced degrees for a significant number of the Nation’s research scientists but that have not been major recipients of NIH support. The goals of the program are to (1) support meritorious research, (2) expose students to research, and (3) strengthen the research environment of the institution. Awards provide limited Direct Costs, plus applicable F&A costs, for periods not to exceed 36 months. This activity code uses multi-year funding authority; however, OER approval is NOT needed prior to an IC using this activity code. |
Environmental Effects On Dermatoxicities of Polycyclic Aromatic Hydrocarbons @ Texas a&M University-Corpus Christi
Project Summary The pollution of polycyclic aromatic hydrocarbons has become a threat in environmental health because of their toxicities to a variety of organisms including humans. Previous epidemiological studies demonstrated a close relationship between PAH exposures and many acute and chronic human diseases. Evidence in the toxicity changes of PAHs under effects of environmental stressors in the past few years raised a bigger concern in the risk of modified PAHs considering the fast-changing environment conditions led by climate change. However, very limited efforts have been made to understand the effects of environmental changes on PAH toxicities to human health. The long-term goal of our study is to understand the molecular mechanism of human inflammatory skin diseases caused by the PAH compounds, and how environmental factors affect the dermatoxicities of these compounds. The central hypothesis of the proposed study is that environmental impacts on structures of PAH compounds will change their toxicities to human skin. Three specific aims will have to be accomplished to complete the test of the hypothesis. The three specific aims include, 1) to identify the photodegradation of aqueous PAHs under the effects of water salinity and acidified water condition initiated by increased atmospheric CO2 level; 2) to discover the dermatoxic pathway of PAHs to human keratinocytes under the environmental impact; and 3) to verify the environment-modified PAH dermatoxic pathway in vivo. To address these specific aims, a standardized PAH protocol will be established in this study. Selected PAH compounds will be degraded under photo exposure within different surrounding salinity and pCO2 levels. These environmental factors are expected to interact with the photodegradation of these chemicals. The toxicities of the PAH chemicals with photo-modification at different salinity and pCO2 levels will be evaluated using three-dimensional human keratinocyte culture and keratinocyte/fibroblast co- culture models. A putative PAH pathogenic pathway in keratinocytes will be validated using the 3D keratinocytes constructs combined with gene functional analyses with siRNA or gene overexpression assays. The relationship between the identified pathway and the skin inflammatory responses will be investigated using a mouse skin inflammation model. As a study in predictive toxicology, the approach of this study takes advantage of the basic knowledge of biological pathways to develop in vitro and animal-based tests to predict adverse effects of chemical exposure, which is a priority component of the Environmental Health Sciences.
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0.942 |
2019 — 2021 |
Xu, Wei |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Protein Arginine Methylation in Breast Cancer @ University of Wisconsin-Madison
PROJECT SUMMARY/ABSTRACT Approximately 30% of all driver genes identified in cancer are related to chromatin structure and function. Distinct from common mechanisms involving altered expression or mutations of epigenetic modifiers, we identified post-translational modification of a chromatin regulator dependent mechanism for cancer progression and metastasis. BAF155, a component of SWI/SNF chromatin remodeling complex, is methylated by arginine methyltransferase CARM1 at a single site, R1064. Using methyl-BAF155 (me- BAF155) specific antibody for ChIP-seq, we found that me-BAF155 binding peaks are enriched with high- density H3K27Ac and H3K4me1 that feature the super-enhancers (SEs). SEs are important regulatory elements controlling oncogene expression in cancer cells. Because SEs recruit bromodomain containing protein BRD4, the expression levels of oncogenes are often sensitive to the BRD4 inhibitor JQ1. We showed that both JQ1 and CARM1 inhibitor treatment blocked the expression of me-BAF155 target genes and the recruitment of me-BAF155 and BRD4 to candidate genes in breast cancer cells. This leads to the hypothesis that me-BAF155 regulates oncogenes addicted to SEs thus promoting cancer metastasis. Aim 1 will examine the global me-BAF155 chromatin association upon treatment with JQ1 and CARM1 inhibitors. Because JQ1 is under clinical investigation for treatment of various cancer types, the novel mechanism of gene regulation via SEs in me-BAF155 driven cancer would suggest new therapeutic means to treat breast cancers with high levels of me-BAF155. We will test our hypothesis using different cell lines and patient- derived xenograft models. Furthermore, integration of microarray and me-BAF155 ChIP-seq data identifies key genes in the Hippo pathway dependent on BAF155 methylation. Therefore, our second hypothesis being tested (Aim 2) is that YAP activity potentiated by me-BAF155 contributes to cell growth, invasion and metastasis. Collectively, our study will validate the functional significance of me-BAF155 in driving cancer metastasis in different pre-clinical models and provide mechanistic insights into the oncogenic functions of me-BAF155. Epigenetic therapy has not been widely used for breast cancer treatment due to the lack of defined target and specific inhibitors for epigenetic enzymes. Our studies will lay solid foundation for the application of epigenetic drugs (e.g. CARM1 inhibitor) that target BAF155 methylation reaction in preventing and treating breast cancer metastasis.
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0.958 |
2020 — 2021 |
Xu, Wei |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Crii: Ri: Learning a Timely Semantic Resource From Social Media Data @ Georgia Tech Research Corporation
One key challenge in text mining and natural language processing research is that a single meaning can be expressed in many different ways, i.e., paraphrases. There has been steady progress towards large paraphrase resources, and a significant increase in its applications: from information retrieval, information extraction, and natural language generation to IBM's Watson, Google's Knowledge Graph, and many more. This research aims to create better paraphrase acquisition techniques and larger scale semantic resources, which could be of great use in various natural language processing tasks and social media data analytics in social science, national security, and other related fields. One example of potential applications is text simplification, which automatically rephrases complex texts into simpler language for children or people with reading disabilities.
The technical innovation of this study focuses on joint modeling of word- and phrase-level alignments between sentence pairs to address the challenges of extracting semantic knowledge from informal data sources (such as social media), which exist in very large quantities rather than just formal sources, such as newswire as per previous work. The model design extends multiple instance learning via two methods, a graphical model and neural network, and can flexibly permit the exploration of different assumptions and models the importance of words or phrases. The modeling advancements can be generalized to other natural language understanding tasks, which require analyzing sentences based on word-level composition or word meaning in a given context, and natural language generation tasks that benefit from learning what words and phrases to remove or rephrase.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
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0.904 |