High Impact Publications

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+┬ámaintains 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+┬ácontrols 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 […]

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 […]