A5069617676- Lymphoma Diagnosis and Treatment
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- CAR-T cell therapy research
- Cutaneous lymphoproliferative disorders research
- Multiple Myeloma Research and Treatments
- Endoplasmic Reticulum Stress and Disease
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- Biochemical and Molecular Research
- Nuclear Structure and Function
- Signaling Pathways in Disease
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- Immune Cell Function and Interaction
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Vascular Tumors and Angiosarcomas
- Genomics and Phylogenetic Studies
- Heat shock proteins research
- Cancer-related gene regulation
- T-cell and Retrovirus Studies
- Genetic factors in colorectal cancer
- 14-3-3 protein interactions
New York Hospital Queens
2021-2024
Cornell University
2016-2024
Weill Cornell Medicine
2017-2024
NewYork–Presbyterian Hospital
2021-2024
Presbyterian Hospital
2021-2024
San Jose State University
2022
Consejo Nacional de Investigaciones Científicas y Técnicas
2017-2019
Instituto de Investigación Médica Mercedes y Martín Ferreyra
2019
Universidad Nacional de Córdoba
2019
Fundación Ciencias Exactas y Naturales
2017-2018
Abstract Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease. Transcriptomic genetic characterization of DLBCL has increased the understanding its intrinsic pathogenesis provided potential therapeutic targets. However, role microenvironment in biology remains less understood. Here, we performed transcriptomic analysis 4,655 DLBCLs from multiple independent cohorts described four major categories that associate with distinct biological aberrations...
Abstract The historical lack of preclinical models reflecting the genetic heterogeneity multiple myeloma (MM) hampers advance therapeutic discoveries. To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-κB, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. Fifteen genetically diverse developed bone marrow (BM) tumors fulfilling pathogenesis. Integrative analyses ∼500...
Given the frequent and largely incurable occurrence of multiple myeloma, identification germline genetic mutations that predispose cells to myeloma may provide insight into disease etiology developmental mechanisms its cell origin, plasma (PC). Here, we identified familial early-onset kindreds with truncating in lysine-specific demethylase 1 (LSD1/KDM1A), an epigenetic transcriptional repressor primarily demethylates histone H3 on lysine 4 regulates hematopoietic stem self-renewal. In...
Patients with Lynch syndrome (LS) are at markedly increased risk for colorectal cancer. It is being increasingly recognised that the immune system plays an essential role in LS tumour development, thus making ideal target cancer prevention. Our objective was to evaluate safety, assess activity and discover novel molecular pathways involved of naproxen as primary secondary chemoprevention patients LS.
Abstract Aberrant splicing is typically attributed to splice‐factor (SF) mutation and contributes malignancies including acute myeloid leukemia (AML). Here, we discovered a mutation‐independent means extensively reprogram alternative (AS). We showed that the dysregulated expression of eukaryotic translation initiation factor eIF4E elevated selective production, thereby impacting multiple spliceosome complexes, factors mutated in AML such as SF3B1 U2AF1. These changes generated landscape...
Abstract Exportin-1 (XPO1), the main soluble nuclear export receptor in eukaryotic cells, is frequently overexpressed diffuse large B-cell lymphoma (DLBCL). A selective XPO1 inhibitor, selinexor, received approval as single agent for relapsed or refractory (R/R) DLBCL. Elucidating mechanisms by which overexpression supports cancer cells could facilitate further clinical development of inhibitors. We uncovered here that increases tolerance to genotoxic stress, leading a poor response...
Methyl-7-guanosine (m7G) "capping" of coding and some noncoding RNAs is critical for their maturation subsequent activity. Here, we discovered that eukaryotic translation initiation factor 4E (eIF4E), itself a cap-binding protein, drives the expression capping machinery increased efficiency ∼100 RNAs. To quantify this, developed enzymatic (cap quantification; CapQ) quantitative cap immunoprecipitation (CapIP) methods. The CapQ method has further advantage it captures information about status...
Selected patients with brain metastases (BM) are candidates for radiotherapy. A lactatogenic metabolism, common in BM, has been associated radioresistance. We demonstrated that BM express nitric oxide (NO) synthase 2 and administration of its substrate l-arginine decreases tumor lactate patients. In a placebo-controlled trial, we showed before each fraction enhanced the effect radiation, improving control BM. Studies preclinical models radiosensitization is NO-mediated mechanism secondary to...
Abstract Resistance to standard immunochemotherapy remains an unmet challenge in diffuse large B-cell lymphoma (DLBCL), and aberrant DNA methylation may contribute chemoresistance. Promising early-phase results were reported with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) plus subcutaneous azacitidine, a hypomethylating agent. In this phase 1 study, we evaluated CC-486 (oral azacitidine) 6 cycles of R-CHOP patients previously untreated intermediate- high-risk...
HSP90 is critical for maintenance of the cellular proteostasis. In cancer cells, also becomes a nucleating site stabilization multiprotein complexes including signaling pathways and transcription complexes. Here we described role this form, referred to as oncogenic HSP90, in regulation cytosolic metabolic proliferating B-cell lymphoma cells. Oncogenic assisted organization enzymes into non-membrane-bound functional compartments. Under experimental conditions that conserved proteostasis,...
The A1 family of eukaryotic aspartic proteinases (APs) forms one the 16 AP families. Although best characterized families, recent increase in genome sequence data has revealed many fungal homologs with novel characteristics. This study was performed to explore space and obtain an in-depth understanding evolution. Using a comprehensive phylogeny approximately 700 sequences from complete proteomes 87 fungi 20 nonfungal eukaryotes, 11 major clades APs were defined which clade I largely...
Background Protein superfamilies can be divided into subfamilies of proteins with different functional characteristics. Their sequences classified hierarchically, which is part sequence function assignation. Typically, there are no clear subfamily hallmarks that would allow pattern-based assignation by this task mostly achieved based on the similarity principle. This hampered lack a score cut-off both sensitive and specific. Results HMMER Cut-off Threshold Tool (HMMERCTTER) adds reliable...
Species of the genus Halomonas are salt-tolerant organisms that have a versatile metabolism and can degrade variety xenobiotic compounds, utilizing them as their sole carbon source. In this study, we examined genome isolate from hydrocarbon-contaminated site to search for chemosensory genes might be responsible observed chemotactic behavior organism well other responses environmental cues.Using genome-wide comparative tools, our was identified strain titanicae (strain KHS3), together with...
The discovery of the human histamine H4 receptor (H4R) has contributed to our understanding role in numerous physiological and pathological conditions, including tumor development progression. lymph nodes patients with malignant lymphomas have shown contain high levels histamine, however, less is known regarding expression function H4R T-cell lymphoma (TCL). In this work we demonstrate isoforms (mRNA protein) three aggressive TCL (OCI-Ly12, Karpas 299, HuT78). Histamine specific agonists...
Abstract The germinal center (GC) dark zone (DZ) and light (LZ) regions spatially separate expansion diversification from selection of antigen-specific B-cells to ensure antibody affinity maturation B cell memory. DZ LZ differ significantly in their immune composition despite the lack a physical barrier, yet determinants this polarization are poorly understood. This study provides novel insights into signals controlling asymmetric T-cell distribution between regions. We identify...
Abstract About 40% of diffuse large B-cell lymphoma (DLBCL) pts do not respond to immunochemotherapy. In human and murine models, we others have shown that the microenvironment (LME) changes with disease progression treatment resistance. This cell-LME co-evolutionary process results in expansion treatment-resistant cells as well reduced infiltration T reprogramming CAFs TAMs into immune suppressive entities. Our analysis relapse or refractory (RR)-DLBCLs showed only an depleted LME but also...
Abstract Bexarotene is a specific retinoid X receptor agonist that has been used for the treatment of cutaneous T-cell lymphoma (CTCL). Because bexarotene causes hypothyroidism, it requires administration levothyroxine. However, levothyroxine, in addition to its ubiquitous nuclear receptors, can activate αVβ3 integrin overexpressed CTCL, potentially interfering antineoplastic effect bexarotene. We thus investigated biological levothyroxine relation treatment. Although isolated CTCL cells...
Eqolisins are rare acid proteases found in archaea, bacteria and fungi. Certain fungi secrete acids as part of their lifestyle interestingly these also have many eqolisin paralogs, up to nine paralogs been recorded. This suggests a process functional redundancy diversification has occurred, which was the subject research we performed describe here.We identified homologs by means iterative HMMER analysis NR database. The sequences were scrutinized for new hallmarks molecular dynamics...