High Impact Publications
TREX2 Exonuclease Causes Spontaneous Mutations and Stress-Induced Replication Fork Defects in Cells Expressing RAD51
January 13, 2021
Abstract: DNA damage tolerance (DDT) and homologous recombination (HR) stabilize replication forks (RFs). RAD18/UBC13/three prime repair exonuclease 2 (TREX2)-mediated proliferating cell nuclear antigen (PCNA) ubiquitination is central to DDT, an error-prone lesion bypass pathway. RAD51 is the recombinase for HR. The RAD51 K133A mutation increased spontaneous mutations and stress-induced RF stalls and nascent strand degradation. […]
PAI-1-dependent inactivation of SMAD4-modulated junction and adhesion complex in obese endometrial cancer
September 9, 2020
Abstract: While plasminogen activator inhibitor-1 (PAI-1) is known to potentiate cellular migration via proteolytic regulation, this adipokine is implicated as an oncogenic ligand in the tumor microenvironment. To understand the underlying paracrine mechanism, here we conduct transcriptomic analysis of 1,898 endometrial epithelial cells (EECs) exposed and unexposed to PAI-1-secreting adipose stromal cells. The PAI-1-dependent action […]
Enhancer RNAs mediate estrogen-induced decommissioning of selective enhancers by recruiting ERa and its cofactor
May 19, 2020
Abstract: The function of enhancer RNAs (eRNAs) in transcriptional regulation remains obscure. By analyzing the genome-wide nascent transcript profiles in breast cancer cells, we identify a special group of eRNAs that are essential for estrogen-induced transcriptional repression. Using eRNAs of TM4SF1 and EFEMP1 as the paradigms, we find that these RNA molecules not only stabilize […]
A Nature Cell Biology article published by a Molecular Medicine team lead by Dr. Jason Liu, reveals a coordinated function for GATA3 and AP1 in altering enhancer landscapes, thereby promoting a basal/mesenchymal phenotype and endocrine resistance in breast cancer.
May 18, 2020
Enhancer reprogramming driven by high-order assemblies of transcription factors promotes phenotypic plasticity and breast cancer endocrine resistance Abstract: Acquired therapy resistance is a major problem for anticancer treatment, yet the underlying molecular mechanisms remain unclear. Using an established breast cancer cellular model, we show that endocrine resistance is associated with enhanced phenotypic plasticity, indicated […]
Nomination for the 2019 Cancer Center Discovery of the Year – Congratulations to Dr. Jason Liu
February 28, 2020
Dr. Jason Liu has been nominated for the Mays Cancer Center 2019 Discovery of the Year Award for his publication, A non-canonical role of YAP/TEAD is required for activation of estrogen-regulated enhancers in breast cancer, in Molecular Cell. Abstract: YAP and TEAD are nuclear effectors of the Hippo signaling pathway that regulates organ size and […]
Acarbose improved survival for Apc+/Min mice
February 20, 2020
Abstract: Acarbose blocks the digestion of complex carbohydrates, and the NIA Intervention Testing Program (ITP) found that it improved survival when fed to mice. Yet, we do not know if lifespan extension was caused by its effect on metabolism with regard to the soma or cancer suppression. Cancer caused death for ~80% of ITP mice. […]
Age-dependent autophagy induction after injury promotes axon regeneration by limiting NOTCH.
January 23, 2020
Abstract: Macroautophagy/autophagy is essential for maintaining cellular homeostasis through the degradation of organelles and proteins. It also has a prominent role in modulating aging. However, the role of autophagy in the neuronal response to axon injury and axon regeneration, particularly in the context of aging, remains largely unknown. Our candidate genetic screen for axon regeneration […]
A Non-canonical Role of YAP/TEAD Is Required for Activation of Estrogen-Regulated Enhancers in Breast Cancer.
January 23, 2020
Abstract: YAP/TEAD are nuclear effectors of the Hippo pathway, regulating organ size and tumorigenesis largely through promoter-associated function. However, their function as enhancer regulators remains poorly understood. Through an in vivo proximity-dependent labeling (BioID) technique, we identified YAP1 and TEAD4 protein as co-regulators of ERα on enhancers. The binding of YAP1/TEAD4 to ERα-bound enhancers is […]
Single-cell proteomic profiling identifies combined AXL and JAK1 inhibition as a novel therapeutic strategy for lung cancer
January 22, 2020
Abstract: Cytometry by time-of-flight (CyTOF) simultaneously measures multiple cellular proteins at the single-cell level and is used to assess inter- and intra-tumor heterogeneity. This approach may be used to investigate the variability of individual tumor responses to treatments. Herein, we stratified lung tumor subpopulations based on AXL signaling as a potential targeting strategy. Integrative transcriptome […]
CENP-A Ubiquitylation Is Indispensable to Cell Viability
January 22, 2020
Abstract: CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity, but how CENP-A is deposited at the centromere remains obscure. We previously reported that CENP-A K124 ubiquitylation, mediated by the CUL4A-RBX1-COPS8 complex, is essential for CENP-A deposition at the centromere. However, a recent report stated that CENP-A K124R mutants show no defects […]