EWSR1 Maintains Centromere Identity

June 27, 2023

Abstract The centromere is essential for ensuring high-fidelity transmission of chromosomes. CENP-A, the centromeric histone H3 variant, is thought to be the epigenetic mark of centromere identity. CENP-A deposition at the centromere is crucial for proper centromere function and inheritance. Despite its importance, the precise mechanism responsible for maintenance of centromere position remains obscure. Here, […]

ROS-Mediated SRMS Activation Confers Platinum Resistance in Ovarian Cancer

April 27, 2023

Abstract Ovarian cancer is the leading cause of death among gynecological malignancies. Checkpoint blockade immunotherapy has so far only shown modest efficacy in ovarian cancer and platinum-based chemotherapy remains the front-line treatment. Development of platinum resistance is one of the most important factors contributing to ovarian cancer recurrence and mortality. Through kinome-wide synthetic lethal RNAi […]

Age-Dependent Loss of Hepatic SIRT1 Enhances NLRP3 Inflammasome Signaling and Impairs Capacity for Liver Fibrosis Resolution

April 24, 2023

Abstract Our studies indicate that the longevity factor SIRT1 is implicated in metabolic disease; however, whether and how hepatocyte-specific SIRT1 signaling is involved in liver fibrosis remains undefined. We characterized a functional link of age-mediated defects in SIRT1 to the NLRP3 inflammasome during age-related liver fibrosis. In multiple experimental murine models of liver fibrosis, we […]

PRC2-mediated epigenetic suppression of type I IFN-STAT2 signaling impairs antitumor immunity in luminal breast cancer

January 11, 2023

Abstract The immunosuppressive tumor microenvironment in some cancer types, such as luminal breast cancer, supports tumor growth and limits therapeutic efficacy. Identifying approaches to induce an immunostimulatory environment could help improve cancer treatment. Here, we demonstrate that inhibition of cancer-intrinsic EZH2 promotes antitumor immunity in estrogen receptor a-positive (ERa+) breast cancer. EZH2 is a component […]

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 […]