About

Ling Cai is an Associate Professor of Pathology at Duke University and a member of the Duke Cancer Institute. She is based at 905 S LaSalle St, GSRB1, Rm 2077, Durham, NC 27710. Her role involves research and teaching within the Department of Pathology, contributing to the academic and clinical missions of Duke University. As a faculty member, she is engaged in advancing understanding in her field, although specific research focus areas are not detailed on the page.

Research topics

• Biology
• Genetics
• Cell biology
• Chemistry
• Cancer research
• Biochemistry
• Surgery
• Organic chemistry
• Nanotechnology
• Materials science
• Molecular biology
• Medicine

Selected publications

• Mono-ubiquitination of histone H2A lysine 119 (H2AK119Ub): its multifaceted role in biology and implication in diseases

  MedScience · 2026-02-01 · 1 citations

  articleOpen access

  Mono-ubiquitination of histone H2A at lysine 119 (H2AK119Ub) is deposited by the Polycomb repressive complex 1 (PRC1) and represents an abundant post-translational modification (PTM) of histones. H2AK119Ub is crucially involved in the regulation of a wide range of biological processes, including organization of the genome into distinct functional domains, gene silencing, and the maintenance of cell identities during development, among others. Biochemically, the deposition and removal of H2AK119Ub are tightly controlled in cells owing to a dynamic balance between the specific "writers" (i.e., PRC1) and "erasers" (i.e., deubiquitinases (DUBs) such as BAP1 and USP16). Furthermore, the increasing evidence establishes a notion that H2AK119Ub serves as a signal for recruiting specific "readers" (such as JARID2, DNMT3A, RYBP, SSX, and RSF1), which elicit the critical downstream effects such as modulating gene transcription, maintaining genome integrity, and shaping cell identity. This H2AK119Ub-based signaling is often perturbed in human diseases, pointing to a connection between its dysregulation and pathological development. This review is aimed at providing a timely, in-depth analysis of the molecular machinery governing H2AK119Ub, its interactions with other chromatin factors, and its causal role in the onset and progression of diseases, notably cancer.

  PublisherDOI

• Figure S2 from The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons of the Transcriptomic Landscapes Across Mouse Models

  2025-05-15

  preprintOpen access1st authorCorresponding

  <p>Top 100 frequent genetic mutations in realworld lung cancer patients</p>

  PublisherDOI

• 500P Darolutamide + androgen-deprivation therapy in Chinese patients with high-risk non-metastatic castration-resistant prostate cancer from the China post-approval commitment study

  Annals of Oncology · 2025-12-01

  article
  PublisherDOI

• YY1 relieves p300 autoinhibition to promote histone acetylation in advanced prostate cancer, enhancing the oncogenic signaling of Androgen Receptor Splice Variant 7

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-06

  preprintOpen accessSenior authorCorresponding

  Abstract Genetic and epigenetic aberrations often act in concert to establish oncogenic transcriptomic programs in aggressive cancers. For example, the development of castration-resistant prostate cancer (CRPC), an advanced prostate cancer form, is closely associated with over-expression and/or hyper-activation of transcription factors (TFs) such as Androgen Receptor (AR) and Yin Yang 1 (YY1), as well as p300, a prominent histone acetyltransferase. How exactly these cancer-related lesions are coordinated to generate a malignant cell state remains elusive. Here, we demonstrate that YY1, which is frequently over-expressed in advanced prostate cancers, allosterically stimulates the acetyltransferase activity of p300 in cis , leading to the globally elevated acetylation of histone H3 lysine 18 and 27 (H3K18ac and H3K27ac). Mechanistically, YY1’s N-terminal activation domain (AD) directly interacts with p300’s TAZ2 domain, relieving the autoinhibition of p300 to facilitate substrate acetylation. Our integrated genome-wide mapping and transcriptomic studies reveal significant co-localization of genomic binding sites of YY1, androgen receptor splice variant 7 (AR-V7, a constitutively active form of AR) and p300 in CRPC cells, where the YY1-mediated p300 activation and resultant histone acetylation increases promote the oncogenic gene-expression programs downstream of YY1 and AR/AR-V7. Both in vitro and in vivo functional assays demonstrate a critical requirement of the above signaling for the advanced disease progression and drug resistance seen in CRPC. Altogether, this study uncovers that YY1 acts to alleviate p300’s autoinhibition at target genes co-bound by oncogenic TFs (YY1 and/or AR/AR-V7) in CRPC, thereby sustaining tumorigenicity. Additionally, the blockade of YY1-mediated gene activation resensitizes CRPC to treatment to the clinic anti-AR agent (enzalutamide), which provides a rationale for overcoming the therapeutic resistance often seen in advanced prostate cancers.

  PublisherOA PDFDOI

• Figure S7 from The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons of the Transcriptomic Landscapes Across Mouse Models

  2025-05-15

  preprintOpen access1st authorCorresponding

  <p>Ascl1 expression across reprocessed RNA-seq datasets</p>

  PublisherDOI

• Figure S3 from A Comparative Study of Neuroendocrine Heterogeneity in Small Cell Lung Cancer and Neuroblastoma

  2025-11-27

  articleOpen access1st authorCorresponding

  <p>Controlling for MYCN amplification status increases the statistical significance of NE score vs. MYCN expression association.</p>

  PublisherOA PDFDOI

• Figure S7 from A Comparative Study of Neuroendocrine Heterogeneity in Small Cell Lung Cancer and Neuroblastoma

  2025-11-27

  articleOpen access1st authorCorresponding

  <p>Comparing NE score-associated features between SCLC and other cancer types.</p>

  PublisherOA PDFDOI

• Figure S4 from A Comparative Study of Neuroendocrine Heterogeneity in Small Cell Lung Cancer and Neuroblastoma

  2025-11-27

  preprintOpen access1st authorCorresponding

  <p>SCLC vs. NBL concordance of NE score association with omics, drug sensitivity, and dependency data.</p>

  PublisherOA PDFDOI

• A selective WDR5 degrader inhibits acute myeloid leukemia in patient-derived mouse models

  UNC Libraries · 2025-11-18

  articleOpen access

  Interactions between WD40 repeat domain protein 5 (WDR5) and its various partners such as mixed lineage leukemia (MLL) and c-MYC are essential for sustaining oncogenesis in human cancers. However, inhibitors that block protein-protein interactions (PPIs) between WDR5 and its binding partners exhibit modest cancer cell killing effects and lack in vivo efficacy. Here, we present pharmacological degradation of WDR5 as a promising therapeutic strategy for treating WDR5-dependent tumors and report two high-resolution crystal structures of WDR5-degrader-E3 ligase ternary complexes. We identified an effective WDR5 degrader via structure-based design and demonstrated its in vitro and in vivo antitumor activities. On the basis of the crystal structure of an initial WDR5 degrader in complex with WDR5 and the E3 ligase von Hippel–Lindau (VHL), we designed a WDR5 degrader, MS67, and demonstrated the high cooperativity of MS67 binding to WDR5 and VHL by another ternary complex structure and biophysical characterization. MS67 potently and selectively depleted WDR5 and was more effective than WDR5 PPI inhibitors in suppressing transcription of WDR5-regulated genes, decreasing the chromatin-bound fraction of MLL complex components and c-MYC, and inhibiting the proliferation of cancer cells. In addition, MS67 suppressed malignant growth of MLL-rearranged acute myeloid leukemia patient cells in vitro and in vivo and was well tolerated in vivo. Collectively, our results demonstrate that structure-based design can be an effective strategy to identify highly active degraders and suggest that pharmacological degradation of WDR5 might be a promising treatment for WDR5-dependent cancers.

  PublisherDOI

• Multiple transactivation domains of EZH2 bind to the TAZ2 domain of p300 and stimulate the acetyltransferase function of p300

  Biochemical Journal · 2025-06-19 · 1 citations

  articleOpen access

  The H3K27me-specific methyltransferase enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of the repressive complex Polycomb repressive complex 2. EZH2 is typically implicated in transcriptional silencing, but it can also activate gene expression. Here, we show that EZH2 contains three adjacent transactivation domains (EZH2TAD) that are recognized by the TAZ2 domain of the transcriptional coactivator and acetyltransferase p300 (p300TAZ2). Binding interfaces identified by chemical shift perturbations in NMR experiments, measurements of binding affinities, and analysis of the complex formation by mass photometry demonstrate that each EZH2TAD can be concomitantly bound by a separate p300TAZ2. Interaction of EZH2TADs with p300TAZ2 stimulates H3K18- and H3K27-specific acetyltransferase activity of p300. We show that in 22Rv1 prostate cancer cells, EZH2 occupies a large set of gene loci lacking H3K27me3, and these non-canonical genomic sites are instead co-occupied by p300, RNA Polymerase II and BRD4 and are rich in histone marks associated with transcriptional activation. Our findings shed light on the potential basis for such a high degree of genetic co-localization through the direct association of p300TAZ2 with EZH2TADs.

  PublisherDOI

Recent grants

• The Role of YY1 in Castration-Resistant Prostate Cancer

  NIH · $2.1M · 2021–2026

Frequent coauthors

• Ralph J. DeBerardinis

  The University of Texas Southwestern Medical Center

  238 shared

• John D. Minna

  195 shared

• Guanghua Xiao

  144 shared

• Yang Xie

  143 shared

• Luc Girard

  80 shared

• Jin Chen

  62 shared

• Gang Greg Wang

  Duke University

  52 shared

• Brandon Faubert

  University of Chicago

  50 shared