- Immunodeficiency and Autoimmune Disorders
- Virus-based gene therapy research
- Immune Response and Inflammation
- Asthma and respiratory diseases
- Mast cells and histamine
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Cell Function and Interaction
- Viral Infectious Diseases and Gene Expression in Insects
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Mitochondrial Function and Pathology
- MicroRNA in disease regulation
- Blood groups and transfusion
- Molecular Biology Techniques and Applications
- Parvovirus B19 Infection Studies
- Advanced Proteomics Techniques and Applications
- IL-33, ST2, and ILC Pathways
- Immunotherapy and Immune Responses
- Infectious Diseases and Mycology
- Monoclonal and Polyclonal Antibodies Research
- Food Allergy and Anaphylaxis Research
- Influenza Virus Research Studies
Massachusetts Institute of Technology
2023
Baylor College of Medicine
1985-2000
University of Alabama at Birmingham
1995
Cleveland Clinic
1995
Methodist Hospital
1985-1991
National Institute of Allergy and Infectious Diseases
1989
National Institutes of Health
1989
Houston Methodist
1985
Howard Hughes Medical Institute
1985
Bipar
1983
Abstract Neuroinflammation is a hallmark of neurodegenerative disorders including Alzheimer's disease (AD). Microglia, the brain's immune cells, express many AD‐risk loci identified in genome wide association studies and present promising target for anti‐inflammatory RNA therapeutics but are difficult to transfect with current methods. Here, several lipid nanoparticle (LNP) formulations examined, lead candidate that supports efficient delivery cultures human stem cell‐derived microglia‐like...
Interferon (IFN) gamma, a cardinal proinflammatory cytokine, induces expression of the gene products class II locus major histocompatibility complex (MHC), whereas IFN-alpha or -beta suppresses MHC expression. The mechanism IFN-beta-mediated inhibition has been unclear. Recently, novel factor termed transactivator (CIITA) identified as essential for IFN-gamma-induced transcription. We studied status CIITA messenger RNA (mRNA) accumulation and CIITA-driven transactivation in IFN-beta-treated...
We have used DNA transfection to identify several regions of the adenovirus genome needed induce replication defective parvovirus, adenovirus-associated virus (AAV). Previous studies indicated that only early functions are aid AAV. In this report, we demonstrate three restriction endonuclease fragments necessary for production infectious AAV in 293-31 cells (an type 5-transformed human embryonic kidney cell line). These map from 28.5 29.4, 59.5 75.9, and 89.7 100 units on 2 correspond...
Pervasive neuroinflammation occurs in many neurodegenerative diseases, including Alzheimer's disease (AD). SPI1/PU.1 is a transcription factor located at genome-wide significant AD-risk locus and its reduced expression associated with delayed onset of AD. We analyzed single-cell transcriptomic datasets from microglia human AD patients found an enrichment PU.1-binding motifs the differentially expressed genes. In hippocampal tissues transgenic mice neurodegeneration, we vastly increased...
Astrocytes are induced by interferon-gamma (IFN-gamma) to express class II major histocompatibility complex (MHC) antigens. Our previous studies demonstrated that IFN-gamma-initiated signaling events important for expression include activation of protein kinase C (PKC) and the Na+/H+ antiporter. We have extended these found tyrosine (PTK) activity is also required expression. Treatment astrocytes with inhibitors specific PKC PTK blocked INF-gamma-induced gene transcription, mRNA expression,...
The three primary capsid proteins (A, B, and C) of adeno-associated viruses have been shown previously to contain overlapping amino acid sequences (R. McPherson J. Rose, Virol. 46:523-529, 1983). In the present study we demonstrate definitively that these are encoded in right half virus 2 genome, one or both smallest RNA species (2.3- 2.6-kilobase RNA) account for their synthesis. Protein A (90 kilodaltons) apparently initiates from a site within intervening sequence, which is intact larger...
Abstract The potential for IL-5 to regulate human B cells is controversial despite its well established role as a regulatory factor murine cells. We hypothesized that the mechanism by which were stimulated would, with cells, determine their respond IL-5. Since Staphylococcus aureus Cowan strain I (SAC) and Moraxella catarrhalis (MCat) stimulate distinct interactions cell-surface Ig, we compared induce an IL-5-responsive state purified homogeneity. Neither SAC alone nor plus Ig production,...
The pharmacological factors involved in lipopolysaccharide (LPS)-induced host resistance against infection were investigated relation to the problem of endotoxin contamination preparations monoclonal antibody common structure endotoxin. When administered prophylactically, purified LPS (as low as 4 ng/kg mouse body weight) or contaminated with (assayed by Limulus amoebocyte lysate test) protective lethal challenge a clinical isolate Escherichia coli (P less than .01). Antibodies that...
Maternally transmitted antigen (Mta) is a murine cell surface class I-like that defined by specific cytotoxic lymphocyte reactivity. Mta unique in its expression requires cooperation between genetic elements both the Qa/Tla region of chromosome 17 and cytoplasm. In view known cytoplasmic, thus maternal, inheritance mitochondria, we have directly assessed their potential involvement expression. The mitochondria-specific lethal dye rhodamine 6G (R6G) was used to control input mitochondria into...
A recombinant plasmid containing a 5.6-kilobase-pair DNA fragment of the Treponema pallidum genome was characterized by endonuclease mapping, and encoded proteins were expressed in Escherichia coli analyzed use vitro transcription translation. One proteins, identified as having molecular weight 37,000 (37K protein), selected for further study. Initially, seroreactivity partially purified 37K antigen demonstrated immunoblotting. After its purification to near homogeneity, cloned T. protein...
IL-5 is an interdigitating homodimeric glycoprotein and a member of the helical bundle family cytokines. potent activator eosinophils specific promoter their differentiation. This activity has implicated in pathogenesis asthma allergic disease. A detailed understanding structure function required to develop immunomodulators IL-5-mediated inflammatory responses. We generated panel neutralizing anti-IL-5 mAbs which were used map functional domains on IL-5. In addition, nucleotide sequences for...
Two substrains of New Zealand Black (NZB) mice have been compared with respect to expression a maternally transmitted cell surface antigen, Mta, defined by cloned cytolytic T cells, and for restriction enzyme polymorphisms mitochondrial DNA (mtDNA). These independent assays maternal cytoplasmic inheritance provide strong evidence genetic contamination the NZB/BlPt substrain (NZB/Bl from Michael Potter's separate colony at National Institutes Health), in which typical NZB immunologic...