- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Protein Kinase Regulation and GTPase Signaling
- Acute Lymphoblastic Leukemia research
- Cell Adhesion Molecules Research
- Acute Myeloid Leukemia Research
- Mitochondrial Function and Pathology
- Cellular Mechanics and Interactions
- Cell death mechanisms and regulation
- Chronic Myeloid Leukemia Treatments
- Metabolism, Diabetes, and Cancer
- Antifungal resistance and susceptibility
- Ubiquitin and proteasome pathways
- Enzyme Production and Characterization
- Cancer Immunotherapy and Biomarkers
- Photosynthetic Processes and Mechanisms
- Receptor Mechanisms and Signaling
- Protein Tyrosine Phosphatases
- Phytase and its Applications
- Platelet Disorders and Treatments
- Lung Cancer Treatments and Mutations
- Genomics and Chromatin Dynamics
- Immunotherapy and Immune Responses
- Chronic Lymphocytic Leukemia Research
University of Chicago
1994-2024
University of Chicago Medical Center
2021
Center for Rheumatology
1998-1999
University of Colorado Denver
1992-1996
National Jewish Health
1992-1996
Howard Hughes Medical Institute
1996
CTLA4 is a cell surface molecule that shares 30% homology with CD28 and binds B7 family members high affinity. Analysis of expression on murine T cells revealed up-regulation after stimulation anti-CD3 mAb in vitro further augmentation the addition exogenous IL-2 or anti-CD28 mAb. The effects were additive part independent, as increased mAb-induced IL-2-deficient mice. In contrast, was only minimally augmented by IL-4, IL-6, IL-7, IL-12. Expression induced inhibited anti-IL-2 plus anti-IL-2R...
Summary Plant cells undergoing programmed cell death (PCD) at late stages typically show chromatin condensation and endonucleolytic cleavage prior to obvious membrane or organelle ultrastructural changes. To investigate possible early PCD‐associated events, we used microscopic observations flow cytometry quantitate mitochondrial potential (ΔΨ m ) changes during PCD the single population levels using Arabidopsis protoplasts. A ΔΨ loss was commonly induced plant important for execution, as...
Abstract The B lymphocyte response to protein Ag is dependent upon the successful presentation T cells of Ag-derived, MHC class II-restricted peptides. cell receptor (BCR) facilitates this process by internalizing ligand and delivering it specialized compartment(s) (MHC II peptide-loading compartments (MIIC)) where processed into peptides loaded onto II. In addition efficiently targeting Ag, BCR can provide tyrosine kinase-dependent signals that augment possibly enhancing generation...
Expression of GTPase-deficient Gi2 alpha subunit (alpha i2) mutant polypeptides and overexpression the wild-type i2 polypeptide in Rat 1a, Swiss 3T3, NIH 3T3 fibroblasts altered normal growth regulation induced a loss contact inhibition. In 1a cells (but not or cells), expression allowed colony formation soft agar, which correlated with anchorage dependence decreased serum requirement. The regulatory properties by was significantly inhibited cotransfection dominant negative Ha-ras...
Functional expressionof recombinant wild-type phosphatase 2A catalytic subunit has been unsuccessful in the past.A nine-amino-acid peptide sequence (YP-YDVPDYA) derived from influenza hemagglutinin protein was used to modify NH2 and/or COOH terminus of subunit.Addition at allowed expression as a predominantly cytosolic enzyme.The 12CAS monoclonal antibody that recognizes immunoprecipitate epitope-tagged subunit.Assay immunoprecipitated demonstrated an okadaic acid-sensitive dephosphorylation...
The peptide C5a which is generated during the complement cascade an important chemotactic factor involved in inflammatory response. receptor (C5aR) primary sequence suggests that it has a serpentine structure of seven transmembrane domains typical classical G‐protein‐coupled receptors. To investigate signal transduction mechanism we transiently expressed C5aR combination with different G‐protein subunits human kidney 293 cells and measured PLC activity induced upon stimulation....
The B cell antigen receptor complex contains heterodimers of Ig-α and Ig-β. cytoplasmic tails each these chains contain two conserved tyrosines, phosphorylation which initiates the signal transduction cascades activated by complex. Although domains Ig-β have been expressed individually demonstrated to be competent units, we postulated that within context a heterodimer, could new, complementary or even synergistic functions. Therefore developed system compare transducing capacities dimers...
GTPase-inhibiting mutations of the alpha subunit (alpha i2) G protein, Gi2, result in constitutive activation i2 signal transduction functions. GTPase-inhibited mutant polypeptides, referred to as gip2 oncoproteins, have glutamine-205 mutated leucine i2Q205L). Expression i2Q205L polypeptide inhibits adenylyl cyclase stimulation, constitutively activates p42 mitogen-activated protein kinase, and transforms Rat 1a fibroblasts. The polypeptides are N-terminal-myristoylated, but function...
Abstract The B cell Ag receptor (BCR) is a multimeric complex, containing Igα and Igβ, capable of internalizing delivering specific Ags to specialized late endosomes, where they are processed into peptides for loading onto MHC class II molecules. By this mechanism, the presentation receptor-selected epitopes T cells enhanced by several orders magnitude. Previously, it has been reported that, under some circumstances, either or Igβ can facilitate Ags. However, we now demonstrate that if these...
Abstract Internal tandem duplication (-ITD) mutations of Fms-like tyrosine kinase 3 (FLT3) provide growth and pro-survival signals in the context established driver FLT3 mutant acute myeloid leukemia (AML). Maternal embryonic leucine zipper (MELK) is an aberrantly expressed gene identified as a target AML. The MELK inhibitor OTS167 induces cell death AML including cells with mutations, yet role mechanisms function are not understood. alone or combination inhibitors (TKIs) were used to...
Expression of GTPase-deficient Gi2 alpha subunit (alpha i2) mutant polypeptides and overexpression the wild-type i2 polypeptide in Rat 1a, Swiss 3T3, NIH 3T3 fibroblasts altered normal growth regulation induced a loss contact inhibition. In 1a cells (but not or cells), expression allowed colony formation soft agar, which correlated with anchorage dependence decreased serum requirement. The regulatory properties by was significantly inhibited cotransfection dominant negative Ha-ras...
We compared Ca2+ signaling and inositol polyphosphate metabolism in NIH-3T3 cells stably transfected with cDNA encoding either the wild-type G protein G16 alpha subunit or a GTPase-deficient 16 (Q212L-alpha 16). Constitutive activation of phosphoinositidase C (PIC) expressing Q212L-alpha was demonstrated by 1) an increased basal level [3H]inositol polyphosphates, 2) enhanced rate accumulation treated 10 mM LiCl, 3) incorporation into cell lipids. had diminished growth rate. Basal...