Andrew L. Hong
A5070914960- Chromatin Remodeling and Cancer
- Cancer Genomics and Diagnostics
- Renal and related cancers
- Bladder and Urothelial Cancer Treatments
- Protein Degradation and Inhibitors
- Cancer Mechanisms and Therapy
- Renal cell carcinoma treatment
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- Advanced Breast Cancer Therapies
- Peptidase Inhibition and Analysis
- Research on Leishmaniasis Studies
- Cancer Research and Treatments
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- CAR-T cell therapy research
- Genetics, Bioinformatics, and Biomedical Research
- Neuroblastoma Research and Treatments
- Cell Image Analysis Techniques
- Pancreatic and Hepatic Oncology Research
- Ferroptosis and cancer prognosis
- Acute Lymphoblastic Leukemia research
- Childhood Cancer Survivors' Quality of Life
Children's Healthcare of Atlanta
2020-2025
Aflac (United States)
2021-2025
Emory University
2020-2025
Dana-Farber Cancer Institute
2014-2024
Center for Cancer and Blood Disorders
2021-2023
Cohen Children's Medical Center
2023
Broad Institute
2014-2021
Boston Children's Hospital
2014-2020
Harvard University
2006-2020
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2014-2020
Pediatric cancers represent a unique case with respect to cancer genomics and precision medicine, as the mutation frequency is low, targeted therapies are less available. Consequently, it unknown whether clinical sequencing can be of benefit.To assess feasibility identifying actionable alterations making individualized therapy (iCat) recommendations in pediatric patients extracranial solid tumors.Clinical study at 4 academic medical centers enrolling between September 5, 2012, November 19,...
Abstract Sequencing of human patient tumors has identified recurrent missense mutations in genes encoding core histones. We report that convert histone H3 amino acid 50 from a glutamate to lysine (H3E50K) support an oncogenic phenotype. Expression H3E50K is sufficient transform cells as evidenced by increase cell migration and invasion, proliferation clonogenicity. also increases the invasive phenotype context co-occurring BRAF mutations, which are present characterized H3E50K. H3E50 lies on...
Alternative splicing of mRNA precursors represents a key gene expression regulatory step and permits the generation distinct protein products with diverse functions. In genome-scale screen for inducers epithelial-to-mesenchymal transition (EMT), we found striking enrichment RNA-binding proteins. We validated that QKI RBFOX1 were necessary sufficient to induce an intermediate mesenchymal cell state increased tumorigenicity. Using RNA-seq eCLIP analysis, coordinately regulated function...
Androgen-receptor (AR) inhibitors, including enzalutamide, are used for treatment of all metastatic castration-resistant prostate cancers (mCRPCs). However, some patients develop resistance or never respond. We find that the transcription factor CREB5 confers enzalutamide in an open reading frame (ORF) expression screen and tumor xenografts. overexpression is essential enzalutamide-resistant patient-derived organoid. In AR-expressing cancer cells, interactions enhance AR activity at a subset...
Malignant rhabdoid tumors (MRT) are highly aggressive pediatric cancers that respond poorly to current therapies. In this study, we screened several MRT cell lines with large-scale RNAi, CRISPR-Cas9, and small-molecule libraries identify potential drug targets specific for these cancers. We discovered MDM2 MDM4, the canonical negative regulators of p53, as significant vulnerabilities. Using two compounds currently in clinical development, idasanutlin (MDM2-specific) ATSP-7041 (MDM2/4-dual),...
Identifying therapeutic targets in rare cancers remains challenging due to the paucity of established models perform preclinical studies. As a proof-of-concept, we developed patient-derived cancer cell line, CLF-PED-015-T, from paediatric patient with undifferentiated sarcoma. Here, confirm that this line recapitulates histology and harbours majority somatic genetic alterations found metastatic lesion isolated at first relapse. We then pooled CRISPR-Cas9 RNAi loss-of-function screens...
BET-bromodomain inhibition (BETi) has shown pre-clinical promise for MYC-amplified medulloblastoma. However, the mechanisms its action, and ultimately resistance, have not been fully defined. Here, using a combination of expression profiling, genome-scale CRISPR/Cas9-mediated loss function ORF/cDNA driven rescue screens, cell-based models spontaneous we identify bHLH/homeobox transcription factors cell-cycle regulators as key genes mediating BETi's response resistance. Cells that acquire...
Few therapies target the loss of tumor suppressor genes in cancer. We examine CRISPR-SpCas9 and RNA-interference loss-of-function screens to identify new therapeutic targets associated with genomic genes. The endosomal sorting complexes required for transport (ESCRT) ATPases VPS4A VPS4B score as strong synthetic lethal dependencies. is essential cancers harboring adjacent SMAD4 on chromosome 18q tumors co-deletion CDH1 (E-cadherin) 16q. demonstrate that more than 30% selectively require or...
Metastasis is a complex and poorly understood process. In pancreatic cancer, loss of the transforming growth factor (TGF)-β/BMP effector SMAD4 correlated with changes in altered histopathological transitions, metastatic disease, poor prognosis. this study, we use isogenic cancer cell lines to identify regulated genes that contribute development colonization. We perform an vivo screen identifying FOSL1 as both target sufficient drive colonization lung. The targeting these early treatment may...
<title>Abstract</title> Chromatin remodeling complexes, such as the SWItch/Sucrose Non-Fermentable (SWI/SNF) complex, play key roles in regulating gene expression by modulating nucleosome positioning. The core subunit SMARCB1 is essential for these functions, it anchors complex to acidic patch, enabling effective chromatin remodeling. While biallelic inactivation of a hallmark several aggressive pediatric malignancies, functional implication missense mutations not fully understood. Current...
Renal medullary carcinoma (RMC) is a rare and deadly kidney cancer in patients of African descent with sickle cell trait. We have developed faithful patient-derived RMC models using whole-genome sequencing, we identified loss-of-function intronic fusion events one SMARCB1 allele concurrent loss the other allele. Biochemical functional characterization these revealed that requires for survival. Through integration RNAi CRISPR-Cas9 genetic screens small-molecule screen, found...
Abstract Developing synchronous bilateral Wilms tumor suggests an underlying (epi)genetic predisposition. Here, we evaluate this predisposition in 68 patients using whole exome or genome sequencing ( n = 85 tumors from 61 with matched germline blood DNA), RNA-seq 99 tumors), and DNA methylation analysis peripheral blood, 29 non-diseased kidney, tumors). We determine the predominant events for predisposition: 1)pre-zygotic genetic variants readily detectable [ WT1 (14.8%), NYNRIN (6.6%) ,...
Every year, approximately 600 infants, children, and adolescents are diagnosed with renal cancer in the United States. In addition to Wilms tumor (WT), which accounts for about 80% of all pediatric cancers, clear cell sarcoma kidney, carcinoma, malignant rhabdoid tumor, as well more rare cancers (other sarcomas, carcinomas, lymphoma) benign tumors can originate within kidney. WT itself be divided into favorable histology (FHWT), a 5-year overall survival (OS) exceeding 90%, anaplastic...