A5028951026- Sarcoma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Cell Adhesion Molecules Research
- Genomics and Chromatin Dynamics
- Telomeres, Telomerase, and Senescence
- Glioma Diagnosis and Treatment
- PARP inhibition in cancer therapy
- RNA Interference and Gene Delivery
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Electrostatic Discharge in Electronics
- Microtubule and mitosis dynamics
- Protease and Inhibitor Mechanisms
- Histone Deacetylase Inhibitors Research
- Acute Lymphoblastic Leukemia research
- Ferroptosis and cancer prognosis
- Cancer Research and Treatments
- Cellular Mechanics and Interactions
- Carcinogens and Genotoxicity Assessment
- Chromatin Remodeling and Cancer
- S100 Proteins and Annexins
Rockefeller University
2020-2025
Memorial Sloan Kettering Cancer Center
2021-2023
Albert Einstein College of Medicine
2014-2019
Yeshiva University
2014-2015
Through its ability to bind the ends of poly(ADP-ribose) (PAR) chains, function histone variant macroH2A1.1, including regulate transcription, is coupled PAR polymerases (PARPs). PARP1 also has a major role in DNA damage response (DDR) signaling, and our results show that macroH2A1 alters kinetics accumulation following acute by both suppressing PARP activity simultaneously protecting chains from degradation. In this way, we demonstrate prevents cellular NAD+ depletion, subsequently...
Abstract BRD4 is a bromodomain-containing transcriptional co-regulator that plays important roles in driving transcription by binding to histone acetyl-lysines at enhancers and promoters while recruiting additional cofactors. While the mechanisms which regulates have been explored, critical acetylations primarily responsible for targeting it chromatin remain unclear. Through machine learning approach, we determined distinct sets of dominate prediction accessibility contexts (e.g. intergenic...
Abstract DNA replication through a challenging genomic landscape is coordinated by the replisome, which must adjust to local conditions provide appropriate speed and respond lesions that hinder its progression. We have previously shown proteasome shuttle proteins, Damage Inducible 1 2 (DDI1/2), regulate Replication Termination Factor (RTF2) levels at stalled replisomes, allowing fork stabilization restart. Here, we show during unperturbed replication, RTF2 regulates replisome localization of...
The histone variant macroH2A1 localizes to two functionally distinct chromatin subtypes marked by either H3K27me3 or H2B acetylations, where it is thought directly regulate transcription. recent finding, that regulates mitochondrial respiration globally dampening PARP activity, requires the field re-evaluate which functions of are due global effects on cellular metabolism and direct determined localization. Here, we demonstrate incorporation into H2B-acetylated a feature in its histone-fold...
S100A4, a member of the S100 family Ca 2+ -binding proteins, is key regulator cell migration and invasion. Our previous studies showed that bone marrow–derived macrophages from S100A4 −/− mice exhibit defects in directional motility chemotaxis vitro reduced recruitment to sites inflammation vivo. We now show loss produces two mechanistically distinct phenotypes with regard macrophage invasion: defect matrix degradation, due disruption podosome rosettes caused by myosin-IIA overassembly,...
Fanconi anemia (FA) is a clinically heterogenous and genetically diverse disease with 22 known complementation groups (FA-A to FA-W), resulting from the inability repair DNA interstrand cross-links. This rare disorder characterized by congenital defects, bone marrow failure, cancer predisposition. FANCA most commonly mutated gene in FA variety of mostly private mutations have been documented, including small large indels point splicing variants. Genotype–phenotype associations are complex,...
Abstract Purpose: Dedifferentiated liposarcoma (DDLS), one of the most common and aggressive sarcomas, infrequently responds to chemotherapy. DDLS survival growth depend on underexpression C/EBPα, a tumor suppressor transcriptional regulator controlling adipogenesis. We sought screen prioritize candidate drugs that increase C/EBPα expression may therefore serve as differentiation-based therapies for DDLS. Experimental Design: screened known bioactive compounds ability restore inhibit...
HMCES, a recently discovered but ancient protein, covalently attaches to damaged single-stranded DNA and shields it from nucleases. Rua-Fernandez colleagues now show that HMCES catalyzes its own recycling, permitting normal growth non-mutagenic repair.1Rua-Fernandez J. Lovejoy C.A. Mehta K.P. Paulin K.A. Toudji Y.T. Eichman B.F. Cortez D. Self-reversal facilitates the resolution of HMCES-DNA protein cross-links in cells.Cell Reports. 2023; 42: 113427Google Scholar Loss base nucleotide...
Abstract Genetic information is duplicated via the highly regulated process of DNA replication. The machinery coordinating this process, replisome, encounters many challenges, including replication fork-stalling lesions that threaten accurate and timely transmission genetic information. Cells have multiple mechanisms to repair or bypass would otherwise compromise 1,2 . We previously shown proteasome shuttle proteins, Damage Inducible 1 2 (DDI1/2) function regulate Replication Termination...
Abstract Oncogene induced senescence (OIS) is an important tumor suppressive mechanism typified by permanent proliferative arrest, a persistent DNA damage response and the senescent-associated secretory phenotype (SASP). MacroH2A1, histone variant that plays roles in several cancer types upregulated during OIS. Our ChIP-seq data demonstrate SASP genes are found macroH2A1-containing chromatin. Additionally, we macroH2A1 critical positive regulator of both transcriptional upregulation ATM...
<p>Copy number, methylation status, and expression of CEBPA in liposarcoma cell lines.</p>
<p>Irinotecan does not cause gross toxicity and induces C/EBPα expression in DDLS tumors vivo, while doxorubicin leads to weight loss.</p>
<p>SN-38/irinotecan suppresses HIF1� expression in vitro and vivo.</p>
<div>AbstractPurpose:<p>Dedifferentiated liposarcoma (DDLS), one of the most common and aggressive sarcomas, infrequently responds to chemotherapy. DDLS survival growth depend on underexpression C/EBPα, a tumor suppressor transcriptional regulator controlling adipogenesis. We sought screen prioritize candidate drugs that increase C/EBPα expression may therefore serve as differentiation-based therapies for DDLS.</p>Experimental Design:<p>We screened known bioactive...
<div>AbstractPurpose:<p>Dedifferentiated liposarcoma (DDLS), one of the most common and aggressive sarcomas, infrequently responds to chemotherapy. DDLS survival growth depend on underexpression C/EBPα, a tumor suppressor transcriptional regulator controlling adipogenesis. We sought screen prioritize candidate drugs that increase C/EBPα expression may therefore serve as differentiation-based therapies for DDLS.</p>Experimental Design:<p>We screened known bioactive...
<p>SN-38 inhibits cell viability and increases expression of C/EBP� in the nucleus DDLS cells.</p>
<p>Copy number, methylation status, and expression of CEBPA in liposarcoma cell lines.</p>
<p>Irinotecan does not cause gross toxicity and induces C/EBPα expression in DDLS tumors vivo, while doxorubicin leads to weight loss.</p>
<p>SN-38/irinotecan suppresses HIF1� expression in vitro and vivo.</p>
<p>SN-38 inhibits cell viability and increases expression of C/EBP� in the nucleus DDLS cells.</p>