News
UT Health San Antonio Snags $11 Million to Fight Cancer
March 16, 2022
HOTTIP Dependent R-loop Formation Regulates CTCF Boundary Activity and TAD Integrity in Leukemia
February 7, 2022
Abstract: HOTTIP lncRNA is highly expressed in acute myeloid leukemia (AML) patients carrying MLL rearrangement or NPM1 mutation to facilitate the formation of HOXA topologically associated domains (TADs) and drive aberrant transcription. However, the mechanism through which HOTTIP accesses CTCF chromatin boundaries and regulates CTCF-mediated genome topology remains unknown. Here, we show that HOTTIP directly […]
2-Hydroxyglutarate destabilizes chromatin regulatory landscape and lineage fidelity to promote cellular heterogeneity
January 27, 2022
Abstract: The epigenome delineates lineage-specific transcriptional programs and restricts cell plasticity to prevent non-physiological cell fate transitions. Although cell diversification fosters tumor evolution and therapy resistance, upstream mechanisms that regulate the stability and plasticity of the cancer epigenome remain elusive. Here we show that 2-hydroxyglutarate (2HG) not only suppresses DNA repair but also mediates the […]
Detecting cancer’s spread before it happens: research indicates it may be possible
October 25, 2021
Cancer that spreads, or metastasizes, to another area of the body is not typically as treatable as the primary tumor from which it originated. Survival from metastatic disease is generally poor. What if a daily or weekly blood sample could monitor each patient’s risk of metastasis, indicating the need for aggressive therapy before cancer spread […]
SNAI2-mediated repression of BIM protects rhabdomyosarcoma from ionizing radiation
September 13, 2021
Abstract Ionizing radiation (IR) and chemotherapy are mainstays of treatment for patients with rhabdomyosarcoma (RMS), yet the molecular mechanisms that underlie the success or failure of radiotherapy remain unclear. The transcriptional repressor SNAI2 was previously identified as a key regulator of IR sensitivity in normal and malignant stem cells through its repression of the proapoptotic […]
Regulation of telomere homeostasis and genomic stability in cancer by N6-adenosine methylation (m6A)
August 9, 2021
Abstract The role of RNA methylation on N6-adenosine (m6A) in cancer has been acknowledged, but the underlying mechanisms remain obscure. Here, we identified the homeobox containing 1 (HMBOX1) as an authentic target mRNA of m6A machinery, which is highly methylated in malignant cells compared to the normal counterparts and subject to expedited degradation upon the […]
Contacts with macrophages promote an aggressive nanomechanical phenotype of circulating tumor cells in prostate cancer.
June 8, 2021
Abstract: Aggressive tumors of epithelial origin shed cells that intravasate and become circulating tumor cells (CTC). The CTCs that are able to survive the stresses encountered in the bloodstream can then seed metastases. We demonstrated previously that CTCs isolated from the blood of prostate cancer patients display specific nanomechanical phenotypes characteristic of cell endurance and […]
HOXBLINC long non-coding RNA activation promotes leukemogenesis in NPM1-mutant acute myeloid leukemia
April 2, 2021
Abstract: Nucleophosmin (NPM1) is the most commonly mutated gene in acute myeloid leukemia (AML) resulting in aberrant cytoplasmic translocation of the encoded nucleolar protein (NPM1c+). NPM1c+ maintains a unique leukemic gene expression program, characterized by activation of HOXA/B clusters and MEIS1 oncogene to facilitate leukemogenesis. However, the mechanisms by which NPM1c+ controls such gene expression patterns to […]
Interaction between SNAI2 and MYOD enhances oncogenesis and suppresses differentiation in Fusion Negative Rhabdomyosarcoma
January 25, 2021
Abstract: Rhabdomyosarcoma (RMS) is an aggressive pediatric malignancy of the muscle, that includes Fusion Positive (FP)-RMS harboring PAX3/7-FOXO1 and Fusion Negative (FN)-RMS commonly with RAS pathway mutations. RMS express myogenic master transcription factors MYOD and MYOG yet are unable to terminally differentiate. Here, we report that SNAI2 is highly expressed in FN-RMS, is oncogenic, blocks […]
Structure and non-canonical Cdk8 activation mechanism within an Argonaute-containing Mediator kinase module
January 19, 2021
Abstract: The dissociable Cdk8 kinase module (CKM) in Mediator, comprising Med13, Med12, CycC, and Cdk8, regulates RNA polymerase II transcription through kinase-dependent and kinase-independent functions. Numerous pathogenic mutations causative for neurodevelopmental disorders and cancer congregate in CKM subunits. However, the structure of the intact CKM and the mechanism by which Cdk8 is noncanonically activated and […]