- ATP Synthase and ATPases Research
- Heat shock proteins research
- MicroRNA in disease regulation
- Immune cells in cancer
- Endoplasmic Reticulum Stress and Disease
- Glioma Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Crystallization and Solubility Studies
- Immune Cell Function and Interaction
- X-ray Diffraction in Crystallography
- Protein Degradation and Inhibitors
- Hormonal Regulation and Hypertension
- Peptidase Inhibition and Analysis
- Histone Deacetylase Inhibitors Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Metal complexes synthesis and properties
- Extracellular vesicles in disease
- Immunotherapy and Immune Responses
- Ubiquitin and proteasome pathways
- Biochemical and Molecular Research
- Tissue Engineering and Regenerative Medicine
- PARP inhibition in cancer therapy
- Ferrocene Chemistry and Applications
- Acute Myeloid Leukemia Research
- Hemophilia Treatment and Research
The Ohio State University
2013-2024
Nationwide Children's Hospital
2021-2024
Zero to Three
2023
Rasmussen College
2021-2022
KU Leuven
2019-2021
The Ohio State University Wexner Medical Center
2021
Center for Neuro-Oncology
2015-2017
University of Ferrara
1999-2017
Neurological Surgery
2015
Azienda Ospedaliera Universitaria Integrata Verona
2014
Significance MicroRNAs (miRNAs) are small, noncoding RNAs regulating gene expression. The aberrant expression of miRNAs is commonly associated with cancer. can be packaged in exosomes/microvesicles secreted by the cells and involved cell-to-cell signaling communication; tumor-secreted promote tumor spread growth surrounding microenvironment. Apoptosis reported to take place wasting muscle cancer cachexia, a debilitating syndrome multiple types cancer, although mechanism remains elusive. This...
Recent studies have shown the importance of dynamic tumor microenvironment (TME) in high-grade gliomas (HGGs). In particular, myeloid cells are known to mediate immunosuppression glioma; however, it is still unclear if play a role low-grade glioma (LGG) malignant progression. Here, we investigate cellular heterogeneity TME using single-cell RNA sequencing murine model that recapitulates progression LGG HGG. LGGs show increased infiltrating CD4
Purpose: HSP90, a highly conserved molecular chaperone that regulates the function of several oncogenic client proteins, is altered in glioblastoma. However, HSP90 inhibitors currently clinical trials are short-acting, have unacceptable toxicities, or unable to cross blood-brain barrier (BBB). We examined efficacy onalespib, potent, long-acting novel inhibitor as single agent and combination with temozolomide (TMZ) against gliomas vitro vivoExperimental Design: The effect onalespib on its...
Abstract Tat, the trans activation protein of HIV, is produced early upon infection to promote and expand HIV replication transmission. However, Tat appears also have effects on target cells, which may affect Ag recognition both during after vaccination. In particular, targets dendritic cells induces their maturation Ag-presenting functions, increasing Th1 T cell responses. We show in this work that modifies catalytic subunit composition immunoproteasomes B either expressing or treated with...
Histone deacetylase inhibitors (HDACi) have proven activity in hematologic malignancies, and their FDA approval multiple myeloma (MM) T-cell lymphoma highlights the need for further development of this drug class. We investigated AR-42, an oral pan-HDACi, a first-in-man phase 1 dose escalation clinical trial. Overall, treatment was well tolerated, no DLTs were evident, MTD defined as 40 mg dosed three times weekly weeks 28-day cycle. One patient each with MM mantle cell demonstrated disease...
// Alessandro Canella 1, * , Hector Cordero Nieves Douglas W. Sborov 2 Luciano Cascione 3 Hanna S. Radomska 1 Emily Smith 4 Andrew Stiff Jessica Consiglio 9 Enrico Caserta Lara Rizzotto Nicola Zanesi Volinia Stefano 5 Balveen Kaur 6 Xiaokui Mo 7 John C. Byrd 8 Yvonne A. Efebera Craig Hofmeister Flavia Pichiorri Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA Oncology/Hematology Fellowship, Lymphoma & Genomics Research Program, IOR...
The majority of hepatitis C virus (HCV)-infected individuals fail to resolve the infection and become chronically infected despite presence HCV-specific CTL responses directed different HCV-derived peptide antigens. Only a minority is able clear by mounting efficient early after acute infection, but at present it not whether viral clearance associated with defined specificity. To elucidate those improvement disease, we analyzed 16 HLA-A2-presented, epitopes in 12 patients, 14 patients...
Abstract A 2‐kDa synthetic derivative of the macrophage‐activating lipopeptide (MALP‐2) from Mycoplasma fermentans is a potent inducer monocytes/macrophages and improves immunogenicity antigens co‐administered by systemic mucosal routes. Dendritic cells (DC) are most antigen‐presenting cells, which able to prime naive T in vivo . To elucidate underlying mechanisms MALP‐2 adjuvanticity, we analyzed its activity on bone marrow‐derived murine DC. In vitro stimulation immature DC with resulted...
The platinum mixed-phosphine complexes (SP-4,2)-[PtCl(8-MTT)(PPh3)(PTA)] (2) and cis-[Pt(8-MTT)2(PPh3)(PTA)] (3) (MTTH2 = 8-(methylthio)theophylline, PTA 1,3,5-triaza-7-phosphaadamantane) have been prepared from the precursor cis-[PtCl2(PPh3)(PTA)] (1), which has fully characterized by X-ray diffraction determination. Antiproliferative activity tests indicated that presence of one lipophilic PPh3 hydrophilic makes 1−3 more active than analogues bearing two or PTA. reactivity...
Multiple myeloma (MM) is a hematological malignancy caused by microenviromentally aided persistence of plasma cells in the bone marrow. The role that extracellular vesicles (EVs), microvesicles and exosomes, released MM have cell-to-cell communication signaling marrow currently unknown. This paper describes proteomic content EVs derived from MM.1S U266 cell lines. First, we compared protein identifications between cellular lysates each line finding large overlap identifications. Next,...
Bio-engineered scaffolds used in orthopedic clinical applications induce different tissue responses after implantation. In this study, non-stoichiometric Mg(2+) ions and stoichiometric apatites, which are surgery as bone substitutes, have been assayed vitro with human adult mesenchymal stem cells (hMSC) to evaluate cytocompatibility osteoconductivity. hMSCs from the marrow aspirates of patients were isolated analyzed by flow cytometry for surface markers Stro1, CD29, CD44, CD71, CD73, CD90,...
Multiple myeloma remains incurable and the majority of patients die within 5 years diagnosis. Reolysin, infusible form human reovirus (RV), is a novel viral oncolytic therapy associated with antitumor activity likely resulting from direct oncolysis virus-mediated immune response. Results our phase I clinical trial investigating single agent Reolysin in relapsed multiple confirmed tolerability, but no objective responses were evident, because virus selectively entered cells did not actively...
Proficient DNA repair by homologous recombination (HR) facilitates resistance to chemoradiation in glioma stem cells (GSC). We evaluated whether compromising HR targeting HSP90, a molecular chaperone required for the function of key proteins, using onalespib, long-acting, brain-penetrant HSP90 inhibitor, would sensitize high-grade gliomas vitro and vivo.The ability onalespib deplete client impair capacity, glioblastoma (GBM) was GSCs, vivo zebrafish mouse intracranial xenograft models. The...
Gliomas are one of the leading causes cancer-related death in adolescent and young adult (AYA) population. Two-thirds AYA glioma patients affected by low-grade gliomas (LGGs), but there no specific treatments. Malignant progression is supported immunosuppressive stromal component tumor microenvironment (TME) exacerbated M2 macrophages a paucity cytotoxic T cells. A single intravenous dose engineered bone-marrow-derived myeloid cells that release interleukin-2 (GEMys-IL2) was used to treat...
Complexes [Pt(mu-N,S-8-TT)(PPh(3))(2)](2) (1), [Pt(mu-S,N-8-TT)(PTA)(2)](2) (2), [Pt(8-TTH)(terpy)]BF(4) (3), cis-[PtCl(8-MTT)(PPh(3))(2)] (4), cis-[Pt(8-MTT)(2)(PPh(3))(2)] (5), cis-[Pt(8-MTT)(8-TTH)(PPh(3))(2)] (6), cis-[PtCl(8-MTT)(PTA)(2)] (7), cis-[Pt(8-MTT)(2)(PTA)(2)] (8), and trans-[Pt(8-MTT)(2)(py)(2)] (9) (8-TTH(2) = 8-thiotheophylline; 8-MTTH 8-(methylthio)theophylline; PTA 1,3,5-triaza-7-phosphaadamantane) are presented studied by IR multinuclear ((1)H, (31)P[(1)H]) NMR...
The new water-soluble ruthenium(II) mononuclear complexes [RuCp(X)(PTA)(L)] (X = 8-thio-theophyllinate (TTH−), L PTA (1), PPh3 (7)); 8-methylthio-theophyllinate (8-MTT−), (2), (8)), 8-benzylthio-theophyllinate (8-BzTT−), (3), (9)) and binuclear [{RuCp(PTA)(L)}2-μ-(Y-κN7,N′7)] (Y bis(S-8-thiotheophyllinate)methane (MBTT2−), (4), (10)), 1,2-bis(S-8-thiotheophyllinate)ethane (EBTT2−), (5), (11)), 1,3-bis(S-8-thiotheophyllinate)propane (PBTT2−); (6), (12)) have been synthesized characterized by...
In several types of thalassemia (including beta(0)39-thalassemia), stop codon mutations lead to premature translation termination and mRNA destabilization through nonsense-mediated decay. Drugs (for instance aminoglycosides) can be designed suppress termination, inducing a ribosomal readthrough. These findings have introduced new hopes for the development pharmacologic approach cure this disease. However, effects aminoglycosides on globin carrying beta-thalassemia not yet been investigated....
Abstract Wharton's jelly from the umbilical cord is a noncontroversial source of mesenchymal stem cells (WJMSCs) with high plasticity, proliferation rate and ability to differentiate towards multiple lineages. WJMSCs different donors have been characterized for their osteogenic potential. Although there large evidence recently scientific debate has focused on MSCs selection, establishing predictable elements discriminate most promising osteoprogenitor cell In present study comparative...
We investigated the spontaneous ribosome readthrough, virtually unexplored in genes encoding secreted proteins, over coagulation F9 nonsense mutations. Expression of recombinant factor IX (FIX) eukaryotic cells demonstrated appreciable levels FIX molecules for mutations p.R162* (5 ± 0.3% rFIX-wt antigen levels), p.R294* (3.1 1.1%) and p.R298* (2.5 0.7%), but not p.L103*. Western blotting revealed a large proportion truncated molecules, which correlated with small amounts full-length...
Low-grade glioma (LGG) is the most common brain tumor affecting pediatric patients (pLGG) and BRAF mutations constitute frequent genetic alterations. Within spectrum of pLGGs, approximately 70%-80% diagnosed with transforming pleomorphic xanthoastrocytoma (PXA) harbor V600E mutation. However, impact cell regulation tumor-infiltrating immune cells their contribution to progression remains unclear. Moreover, efficacy inhibitors in treating pLGGs limited compared on BRAF-mutated melanoma. Here...
The 26S proteasome is a multicatalytic protease complex that plays an essential role in intracellular protein degradation. We have synthesized and tested series of arecoline peptide derivatives where the portion derives from screening tripeptide sequences, moiety has been considered as potential substrate for catalytic threonine. Derivatives 17-19 are best compounds series, showing chymotryptic-like (beta5) inhibition (IC(50) congruent with 1 microM) favorable pharmacokinetic properties.