A5054946015- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Neuroblastoma Research and Treatments
- Melanoma and MAPK Pathways
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Cutaneous Melanoma Detection and Management
- RNA modifications and cancer
- Colorectal Cancer Treatments and Studies
- Single-cell and spatial transcriptomics
- Birth, Development, and Health
- CAR-T cell therapy research
- RNA and protein synthesis mechanisms
- Advanced Breast Cancer Therapies
- Lung Cancer Treatments and Mutations
- Cancer-related molecular mechanisms research
- Reproductive System and Pregnancy
- RNA Research and Splicing
- Cancer, Hypoxia, and Metabolism
- Ferroptosis and cancer prognosis
- Molecular Biology Techniques and Applications
- Glioma Diagnosis and Treatment
Stanford University
2022-2025
Dartmouth College
2017-2023
Baylor College of Medicine
2020-2023
Houston Institute for Clinical Research
2021-2023
Dartmouth–Hitchcock Medical Center
2018
Brandeis University
2017
Negative checkpoint regulators (NCRs) temper the T cell immune response to self-antigens and limit development of autoimmunity. Unlike all other NCRs that are expressed on activated lymphocytes, V-type immunoglobulin domain-containing suppressor activation (VISTA) is naïve cells. We report an unexpected heterogeneity within compartment in mice, where loss VISTA disrupted major quiescent subset enhanced self-reactivity. Agonistic engagement increased tolerance by promoting antigen-induced...
Autoimmune diseases disproportionately affect females more than males. The XX sex chromosome complement is strongly associated with susceptibility to autoimmunity. Xist long non-coding RNA (lncRNA) expressed only in randomly inactivate one of the two X chromosomes achieve gene dosage compensation. Here, we show that ribonucleoprotein (RNP) complex comprising numerous autoantigenic components an important driver sex-biased Inducible transgenic expression a non-silencing form male mice...
Abstract Extrachromosomal DNA (ecDNA) presents a major challenge for cancer patients. ecDNA renders tumours treatment resistant by facilitating massive oncogene transcription and rapid genome evolution, contributing to poor patient survival 1–7 . At present, there are no ecDNA-specific treatments. Here we show that enhancing transcription–replication conflict enables targeted elimination of ecDNA-containing cancers. Stepwise analyses reveal pervasive RNA associated single-stranded DNA,...
Abstract Background: Lung cancer is associated with the highest mortality rate of all types, and most common histologic subtype lung adenocarcinoma. To apply more effective therapeutic treatment, molecular markers that are able to predict recurrence risk patients adenocarcinoma critically needed. Mutations in TP53 tumor suppressor gene have been found approximately 50% cases, but presence a mutation does not always associate increased mortality. Methods: The Cancer Genome Atlas RNA...
Intra-tumor heterogeneity stems from genetic, epigenetic, functional, and environmental differences among tumor cells. A major source of genetic comes DNA sequence and/or whole chromosome focal copy number variations (CNVs). Whole CNVs are caused by chromosomal instability (CIN) that is defined a persistently high rate mis-segregation. Accordingly, CIN causes constantly changing karyotypes result in extensive cell-to-cell heterogeneity. How the influences gene expression individual cells...
Abstract Four out of five patients with autoimmune diseases are women. The XIST ribonucleoprotein (RNP) complex, comprising the female-specific long noncoding RNA and over 100 associated proteins, may drive several that disproportionately affect women, who have elevated levels autoantibodies against RNP. However, structural distribution, potential origin, clinical significance RNP remained unexplored. Here, we find is autoantigens six female-biased conditions. Mapping autoantibody targets to...
Abstract Genome conformation underlies transcriptional regulation by distal enhancers, and genomic rearrangements in cancer can alter critical regulatory interactions. Here we profiled the 3D genome architecture enhancer connectome of 69 tumor samples spanning 15 primary human types from The Cancer Atlas (TCGA). We discovered three archetypes usage for over one hundred oncogenes across cancers: static, selective gain, or dynamic rewiring. Integrative analyses revealed landscape non-cancer...
Melanoma is the most aggressive type of skin cancer in United States with an increasing incidence. lesions often exhibit high immunogenicity, infiltrating immune cells playing important roles regression tumors occurring spontaneously or caused by therapeutic treatment. Computational and experimental methods have been used to estimate abundance tumors, but their applications are limited requirement large gene sets multiple antibodies. Although prognostic role has appreciated, a systematic...
Abstract Neoadjuvant chemotherapy is the current standard of care for large, advanced, and/or inoperable tumors, including triple‐negative breast cancer. Although clinical benefits neoadjuvant have been illustrated through numerous trials, more than half patients do not experience therapeutic benefit and needlessly suffer from side effects. Currently, no clinically applicable biomarkers are available predicting response in cancer; discovery such a predictive biomarker or marker profile an...
Extrachromosomal DNA (ecDNA) amplifications are prevalent drivers of human cancers. We show that ecDNAs exhibit elevated structural variants leading to gene fusions produce oncogene fusion transcripts. The long noncoding RNA (lncRNA) PVT1 is the most recurrent variant across cancer genomes, with PVT1-MYC arising frequently on ecDNA. exon 1 predominant 5' partner fused MYC or other oncogenes 3' end. Mechanistic studies demonstrate confers enhanced stability for transcripts, which requires...
Abstract Background Estriol (E 3 ) is a steroid hormone formed only during pregnancy in primates including humans. Although E synthesized at large amounts through complex pathway involving the fetus and placenta, it not required for maintenance of has classically been considered virtually inactive due to associated very weak canonical estrogen signaling. However, exposure may have an effect on organs both within outside reproductive system, compounds with binding affinity receptors weaker...
Abstract Extrachromosomal DNA (ecDNA) presents a major challenge for precision medicine, contributing to poor survival patients with oncogene-amplified tumours. EcDNA renders tumours resistant targeted treatments by facilitating massive transcription of oncogenes and rapid genome evolution. At present, there are no ecDNA- specific treatments. Here we show that enhancing replication conflict enables elimination ecDNA-containing cancers, exposing an actionable vulnerability. Stepwise analyses...
To identify cancer-associated gene regulatory changes, we generated single-cell chromatin accessibility landscapes across eight tumor types as part of The Cancer Genome Atlas. Tumor is strongly influenced by copy number alterations that can be used to subclones, yet underlying cis-regulatory retain cancer type-specific features. Using organ-matched healthy tissues, identified the "nearest healthy" cell in diverse cancers, demonstrating signature basal-like-subtype breast most similar...
Abstract Background Neuroblastoma (NB) is a heterogeneous disease with respect to genomic abnormalities and clinical behaviors. Despite recent advances in our understanding of the association between genetic aberrations features, it remains one major challenges predict prognosis stratify patients for determining personalized therapy this disease. The aim study was develop an effective prediction model NB patients. Methods We integrated diverse computational analyses define gene signatures...
EGFR is an oncogene with a high frequency of activating mutations in nonsmall cell lung cancer (NSCLC). inhibitors have been FDA-approved for NSCLC and shown efficacy patients certain mutations. However, only 9% to 26% these achieve objective responses. In our study, we developed gene signature based on The Cancer Genome Atlas (TCGA) RNA-seq data adenocarcinoma (LUAD) direct the preselection more effective EGFR-targeted therapy. This infers baseline signaling pathway activity (denoted as...
Huntington's disease is caused by the pathological expansion of a polyglutamine (polyQ) stretch in Huntingtin (Htt), but molecular mechanisms which polyQ Htt causes toxicity selective neuronal populations remain poorly understood. Interestingly, heterologous expression expanded toxic Saccharomyces cerevisiae cells, has no effect Schizosaccharomyces pombe, related yeast species possessing very few endogenous or Q/N-rich proteins. Here, we used comprehensive and unbiased mass spectrometric...
Transcription factor (TF) STAT3 contributes to pancreatic cancer progression through its regulatory roles in both tumor cells and the microenvironment (TME). In this study, we performed a systematic analysis of all TFs patient-derived gene expression datasets confirmed as critical regulator TME. Importantly, developed novel framework that is based on TF target distinguish between environmental- tumor-specific activities studies. Using framework, our results novelly showed...
Abstract Background Neuroblastoma (NB) is the most common extracranial solid tumor found in children. The frequent gain/loss of many chromosome bands cells and absence mutations at diagnosis suggests that NB a copy number-driven cancer. Despite previous work, systematic analysis investigates relationship between such patient prognosis has yet to be implemented. Methods First, we analyzed two CNV datasets select chromosomal with high frequency gain or loss. Second, applied computational...
c-MYC (MYC) is deregulated in more than 50% of all cancers. While MYC amplification the most common MYC-deregulating event, many other alterations can increase activity. We thus systematically investigated pathway activity across different tumor types. Using a logistic regression framework, we established type-specific, transcriptomic-based scores that accurately capture show reflect variety MYC-regulating mechanisms, including MYCL and/or MYCN amplification, promoter methylation, mRNA...