A5091039685- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- RNA modifications and cancer
- Lymphoma Diagnosis and Treatment
- Advanced biosensing and bioanalysis techniques
- Chronic Lymphocytic Leukemia Research
- RNA Interference and Gene Delivery
- Lung Cancer Treatments and Mutations
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Protease and Inhibitor Mechanisms
- Acute Lymphoblastic Leukemia research
- Chronic Myeloid Leukemia Treatments
- IgG4-Related and Inflammatory Diseases
- Food Allergy and Anaphylaxis Research
- Amino Acid Enzymes and Metabolism
- Acute Myeloid Leukemia Research
- Phagocytosis and Immune Regulation
- RNA regulation and disease
- Surface Chemistry and Catalysis
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Calcium signaling and nucleotide metabolism
- Autoimmune and Inflammatory Disorders Research
- Occupational and environmental lung diseases
University of Illinois Chicago
2023-2024
University of Illinois Hospital & Health Sciences System
2024
Illinois College
2023
University of Michigan
2014-2020
Sylvester Comprehensive Cancer Center
2018
University of Miami
2018
Jackson Memorial Hospital
2017
University of Rochester Medical Center
2015
University of Chicago
2007-2012
Case Western Reserve University
2007
Heterozygous mutations encoding abnormal forms of the death receptor Fas dominantly interfere with Fas-induced lymphocyte apoptosis in human autoimmune lymphoproliferative syndrome. This effect, rather than depending on ligand-induced oligomerization, was found to stem from ligand- independent interaction wild-type and mutant receptors through a specific region extracellular domain. Preassociated complexes were living cells by means fluorescence resonance energy transfer between variants...
RNA represents a prominent class of biomolecules. Present in all living systems, plays many essential roles gene expression, regulation, and development. Accordingly, biological processes depend on the accurate enzymatic processing, modification, cleavage RNA. Understanding catalytic mechanisms these enzymes therefore an important goal defining systems at molecular level.In this context, molecules bearing 3′- or 5′-S-phosphorothiolate linkages comprise what are arguably among most incisive...
Antibodies that bind protein antigens are indispensable in biochemical research and modern medicine. However, knowledge of RNA-binding antibodies their application the ever-growing RNA field is lacking. Here we have developed a robust approach using synthetic phage-display library to select specific antigen-binding fragments (Fabs) targeting large functional RNA. We solved crystal structure first Fab-RNA complex at 1.95 A. Capability phasing contact formation suggests Fab provides...
Existing evidence suggests that the Varkud satellite (VS) ribozyme accelerates cleavage of a specific phosphodiester bond using general acid-base catalysis. The key functionalities are nucleobases adenine 756 in helix VI ribozyme, and guanine 638 substrate stem loop. This results bell-shaped dependence reaction rate on pH, corresponding to groups with p K = 5.2 8.4. However, it is not possible from those data determine which nucleobase acid, base. We have therefore made substrates 5′ oxygen...
Within the three-dimensional architectures of RNA molecules, divalent metal ions populate specific locations, shedding their water molecules to form chelates. These interactions help adopt and maintain conformations frequently make essential contributions function. Defining locations these site-bound remains challenging despite growing database structures. Metal-ion rescue experiments have provided a powerful approach identify distinguish catalytic within active sites, but ability such that...
Lack of sufficient quantities isotopically labeled materials has precluded the use heavy atom isotope effects to investigate mechanisms nucleotidyl transfer reactions in nucleic acids. Here we achieve regioselective opening 2,2'-cyclouridine with [(18)O2]benzoic acid/potassium hydride, allowing an efficient "one-pot" synthesis [2'-18O]uridine 88% yield. Conversion corresponding phosphoramidite enables solid-phase [2'-(18)O] RNA substrates for effect studies transferases and hydrolases.
Oligoribonucleotides containing a 5′-phosphorothiolate linkage have provided effective tools to study the mechanisms of RNA catalysis, allowing resolution kinetic ambiguity associated with mechanistic dissection and providing strategy establish between catalysis specific functional groups. However, challenges their synthesis limited wider application these modified nucleic acids. Here, we describe general semisynthetic obtain oligoribonucleotides reliably relatively efficiently. The approach...
This work describes a general method for the synthesis of oligoribonucleotides containing site-specific nonbridging phosphorodithioate linkage via automated solid-phase using 5'-O-DMTr-2'-O-TBS-ribonucleoside 3'-N,N-dimethyl-S-(2,4-dichlorobenzyl) phosphorothioamidites (2a-2d). The 3'-phosphorothioamidites (2a-2d) can be conveniently prepared in good yields (86-99%) one-pot reaction from corresponding 5'-O-DMTr-2'-O-TBS-ribonucleosides (1a-1d).
Philadelphia chromosome-like (Ph-like) genetic alterations define a subset of B lymphoblastic leukemia/lymphoma (B-ALL), which represents separate provisional entity in the World Health Organization 2016 updated classification. However, these have not been described outside context B-ALL.Cytogenomic array and molecular analysis identified Ph-like signature mixed-phenotype acute leukemia (MPAL), B/myeloid, confirmed using conventional immunophenotypic cytochemical analysis.Flow cytometry...
Systemic mastocytosis (SM) is characterized by a clonal proliferation of aberrant mast cells within extracutaneous sites. In subset SM cases, second associated hematologic non‐mast cell disease (AHNMD) also present, usually myeloid origin. Polymerase chain reaction and targeted fluorescence in situ hybridization studies have provided evidence that, at least some the are related clonally to neoplastic AHNMD. this work, single nucleotide polymorphism microarray (SNP‐A) was used characterize...
Abstract Introduction/Objective Fibrin-associated large B-cell lymphoma (FA-LBCL) is a proliferation of EBV-positive B- cells in association with fibrinous debris, typically the context prostheses, hematomas, pseudocysts and myxomas. It newly described entity extremely rare, no deaths reported as direct result. indolent not visible on imaging, instead being found incidentally microscopy. mainly diagnosis exclusion characterized by sheets neoplastic lymphocytes contained within fibrin...
A fundamental requirement for growth of rapidly proliferating cells is metabolic adaptation to promote synthesis biomass 1 . ATP citrate lyase (ACLY) a critical enzyme responsible cytosolic acetyl-CoA, the key building component de novo fatty acid and links vital pathways such as carbohydrate lipid metabolism 2 The mechanisms ACLY regulation are not completely understood function by tyrosine phosphorylation unknown. Here we show using mass-spectrometry-driven phosphoproteomics metabolomics...