441 results match your criteria: "Hamon Center for Regenerative Science and Medicine.[Affiliation]"

Coactivator condensation drives cardiovascular cell lineage specification.

Sci Adv

March 2024

Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

During development, cells make switch-like decisions to activate new gene programs specifying cell lineage. The mechanisms underlying these decisive choices remain unclear. Here, we show that the cardiovascular transcriptional coactivator myocardin (MYOCD) activates cell identity genes by concentration-dependent and switch-like formation of transcriptional condensates.

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Neuroblastoma poses significant challenges in clinical management. Despite its relatively low incidence, this malignancy contributes disproportionately to cancer-related childhood mortality. Tailoring treatments based on risk stratification, including MYCN oncogene amplification, remains crucial, yet high-risk cases often confront therapeutic resistance and relapse.

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ZNF692 regulates nucleolar morphology by interacting with NPM1 and modifying its self-assembly properties.

J Biol Chem

March 2024

Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Electronic address:

The nucleolus, a membrane-less organelle, is responsible for ribosomal RNA transcription, ribosomal RNA processing, and ribosome assembly. Nucleolar size and number are indicative of a cell's protein synthesis rate and proliferative capacity, and abnormalities in the nucleolus have been linked to neurodegenerative diseases and cancer. In this study, we demonstrated that the nucleolar protein ZNF692 directly interacts with nucleophosmin 1 (NPM1).

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Hallmarks of totipotent and pluripotent stem cell states.

Cell Stem Cell

March 2024

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address:

Though totipotency and pluripotency are transient during early embryogenesis, they establish the foundation for the development of all mammals. Studying these in vivo has been challenging due to limited access and ethical constraints, particularly in humans. Recent progress has led to diverse culture adaptations of epiblast cells in vitro in the form of totipotent and pluripotent stem cells, which not only deepen our understanding of embryonic development but also serve as invaluable resources for animal reproduction and regenerative medicine.

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NG2 glia reprogramming induces robust axonal regeneration after spinal cord injury.

iScience

February 2024

Department of Neurological Surgery, Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Spinal cord injury (SCI) often leads to neuronal loss, axonal degeneration, and behavioral dysfunction. We recently show that reprogramming of NG2 glia produces new neurons, reduces glial scaring, and ultimately leads to improved function after SCI. By examining endogenous neurons, we here unexpectedly uncover that NG2 glia reprogramming also induces robust axonal regeneration of the corticospinal tract and serotonergic neurons.

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4D Light-sheet Imaging of Zebrafish Cardiac Contraction.

J Vis Exp

January 2024

Department of Bioengineering, The University of Texas at Dallas; Center for Imaging and Surgical Innovation, The University of Texas at Dallas; Hamon Center for Regenerative Science and Medicine, UT Southwestern Medical Center;

Zebrafish is an intriguing model organism known for its remarkable cardiac regeneration capacity. Studying the contracting heart in vivo is essential for gaining insights into structural and functional changes in response to injuries. However, obtaining high-resolution and high-speed 4-dimensional (4D, 3D spatial + 1D temporal) images of the zebrafish heart to assess cardiac architecture and contractility remains challenging.

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Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children and adolescents. Fusion-negative RMS (FN-RMS) accounts for more than 80% of all RMS cases. The long-term event-free survival rate for patients with high-grade FN-RMS is below 30%, highlighting the need for improved therapeutic strategies.

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Kinome-wide siRNA screen identifies a DCLK2-TBK1 oncogenic signaling axis in clear cell renal cell carcinoma.

Mol Cell

February 2024

Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:

TANK-binding kinase 1 (TBK1) is a potential therapeutic target in multiple cancers, including clear cell renal cell carcinoma (ccRCC). However, targeting TBK1 in clinical practice is challenging. One approach to overcome this challenge would be to identify an upstream TBK1 regulator that could be targeted therapeutically in cancer specifically.

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Screens in aging-relevant human ALS-motor neurons identify MAP4Ks as therapeutic targets for the disease.

Cell Death Dis

January 2024

Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Effective therapeutics is much needed for amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease mainly affecting motor neurons. By screening chemical compounds in human patient-derived and aging-relevant motor neurons, we identify a neuroprotective compound and show that MAP4Ks may serve as therapeutic targets for treating ALS. The lead compound broadly improves survival and function of motor neurons directly converted from human ALS patients.

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Microglia, as the immune cells of the central nervous system (CNS), play dynamic roles in both health and diseased conditions. The ability to genetically target microglia using viruses is crucial for understanding their functions and advancing microglia-based treatments. We here show that resident microglia can be simply and specifically targeted using adeno-associated virus (AAV) vectors containing a 466-bp DNA fragment from the human () promoter.

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Econazole selectively induces cell death in NF1-homozygous mutant tumor cells.

Cell Rep Med

December 2023

Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA; Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; O'Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address:

Cutaneous neurofibromas (cNFs) are tumors that develop in more than 99% of individuals with neurofibromatosis type 1 (NF1). They develop in the dermis and can number in the thousands. cNFs can be itchy and painful and negatively impact self-esteem.

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Dissecting embryonic and extraembryonic lineage crosstalk with stem cell co-culture.

Cell

December 2023

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:

Embryogenesis necessitates harmonious coordination between embryonic and extraembryonic tissues. Although stem cells of both embryonic and extraembryonic origins have been generated, they are grown in different culture conditions. In this study, utilizing a unified culture condition that activates the FGF, TGF-β, and WNT pathways, we have successfully derived embryonic stem cells (FTW-ESCs), extraembryonic endoderm stem cells (FTW-XENs), and trophoblast stem cells (FTW-TSCs) from the three foundational tissues of mouse and cynomolgus monkey (Macaca fascicularis) blastocysts.

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Murine Orchiectomy and Ovariectomy to Reduce Sex Hormone Production.

J Vis Exp

November 2023

Department of Ophthalmology, UT Southwestern Medical Center; Department of Molecular Biology, UT Southwestern Medical Center; Hamon Center for Regenerative Science and Medicine, UT Southwestern Medical Center; Peter O'Donnell Jr. Brain Institute, UT Southwestern Medical Center;

Sex hormone signaling plays a critical role in multiple organ systems as well as in the progression of various diseases, including neurodegenerative disease. The manipulation of sex hormone levels in the murine model system allows for the study of their impact on organs/tissues and within disease progression. Orchiectomy - the surgical removal of the testes - and ovariectomy - the surgical removal of the ovaries - provide a method to deplete the endogenous sex hormones so that the precise hormone levels can be provided through drug or other delivery methods.

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Prostate cancer (PCa) is primarily driven by aberrant Androgen Receptor (AR) signaling. Although there has been substantial advancement in antiandrogen therapies, resistance to these treatments remains a significant obstacle, often marked by continuous or enhanced AR signaling in resistant tumors. While the dysregulation of the ubiquitination-based protein degradation process is instrumental in the accumulation of oncogenic proteins, including AR, the molecular mechanism of ubiquitination-driven AR degradation remains largely undefined.

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Transcription factor NFYa controls cardiomyocyte metabolism and proliferation during mouse fetal heart development.

Dev Cell

December 2023

Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine and Sen. Paul D. Wellstone Muscular Dystrophy Specialized Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. Electronic address:

Cardiomyocytes are highly metabolic cells responsible for generating the contractile force in the heart. During fetal development and regeneration, these cells actively divide but lose their proliferative activity in adulthood. The mechanisms that coordinate their metabolism and proliferation are not fully understood.

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DWORF Extends Life Span in a PLN-R14del Cardiomyopathy Mouse Model by Reducing Abnormal Sarcoplasmic Reticulum Clusters.

Circ Res

December 2023

Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands (N.M.S., T.R.E., V.O.N.T., A.M.F., E.M.S., R.A.d.B., H.H.W.S.).

Background: The p.Arg14del variant of the (phospholamban) gene causes cardiomyopathy, leading to severe heart failure. Calcium handling defects and perinuclear PLN aggregation have both been suggested as pathological drivers of this disease.

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A domain of all trades: The enzymatic versatility of the NiRAN domain.

Mol Cell

November 2023

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address:

The SARS-CoV-2 NiRAN domain is essential for viral replication. Despite adopting a pseudokinase fold, it catalyzes three distinct biochemical reactions from a single active site. In this issue of Molecular Cell, Small et al.

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RBPMS regulates cardiomyocyte contraction and cardiac function through RNA alternative splicing.

Cardiovasc Res

February 2024

Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390, USA.

Aims: RNA binding proteins play essential roles in mediating RNA splicing and are key post-transcriptional regulators in the heart. Our recent study demonstrated that RBPMS (RNA binding protein with multiple splicing) is crucial for cardiac development through modulating mRNA splicing, but little is known about its functions in the adult heart. In this study, we aim to characterize the post-natal cardiac function of Rbpms and its mechanism of action.

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Cardiovascular diseases are the most common cause of worldwide morbidity and mortality, highlighting the necessity for advanced therapeutic strategies. Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ) is a prominent inducer of various cardiac disorders, which is mediated by 2 oxidation-sensitive methionine residues within the regulatory domain. We have previously shown that ablation of CaMKIIδ oxidation by CRISPR-Cas9 base editing enables the heart to recover function from otherwise severe damage following ischemia/reperfusion (IR) injury.

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ZNF692 organizes a hub specialized in 40S ribosomal subunit maturation enhancing translation in rapidly proliferating cells.

Cell Rep

October 2023

Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:

Increased nucleolar size and activity correlate with aberrant ribosome biogenesis and enhanced translation in cancer cells. One of the first and rate-limiting steps in translation is the interaction of the 40S small ribosome subunit with mRNAs. Here, we report the identification of the zinc finger protein 692 (ZNF692), a MYC-induced nucleolar scaffold that coordinates the final steps in the biogenesis of the small ribosome subunit.

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Key transcriptional effectors of the pancreatic acinar phenotype and oncogenic transformation.

PLoS One

November 2023

Department of Molecular Biology and the Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.

Proper maintenance of mature cellular phenotypes is essential for stable physiology, suppression of disease states, and resistance to oncogenic transformation. We describe the transcriptional regulatory roles of four key DNA-binding transcription factors (Ptf1a, Nr5a2, Foxa2 and Gata4) that sit at the top of a regulatory hierarchy controlling all aspects of a highly differentiated cell-type-the mature pancreatic acinar cell (PAC). Selective inactivation of Ptf1a, Nr5a2, Foxa2 and Gata4 individually in mouse adult PACs rapidly altered the transcriptome and differentiation status of PACs.

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Mapping Cellular Interactions from Spatially Resolved Transcriptomics Data.

bioRxiv

January 2024

Quantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Article Synopsis
  • Cell-cell communication (CCC) is crucial for understanding how organisms function, and new spatially resolved transcriptomics technologies (SRTs) enable detailed mapping of gene interactions at the single-cell level, though data complexity remains a challenge.* -
  • The spacia framework utilizes a Bayesian multi-instance learning approach to detect CCCs, overcoming limitations of existing analytical tools by maintaining single-cell resolution and considering multiple senders and receivers.* -
  • Spacia's application across various single-cell SRT technologies revealed important insights into cellular behavior in cancer, such as the roles of different immune cells in prostate cancer and their correlation with patient outcomes.*
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Spinal cord injuries (SCIs) can lead to significant neurological deficits and lifelong disability, with far-reaching physical, psychological, and economic consequences for affected individuals and their families. Current treatments for SCIs are limited in their ability to restore function, and there is a pressing need for innovative therapeutic approaches. Stem cell therapy has emerged as a promising strategy to promote the regeneration and repair of damaged neural tissue following SCIs.

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