A5040657862- Ion Channels and Receptors
- Biochemical Analysis and Sensing Techniques
- Olfactory and Sensory Function Studies
- interferon and immune responses
- Ocular Diseases and Behçet’s Syndrome
- Systemic Lupus Erythematosus Research
- Hereditary Neurological Disorders
- Immune cells in cancer
- Ion channel regulation and function
- Connexins and lens biology
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Chemical Sensor Technologies
- Pain Mechanisms and Treatments
- Allergic Rhinitis and Sensitization
- Vector-borne infectious diseases
- RNA regulation and disease
- Coenzyme Q10 studies and effects
- Asthma and respiratory diseases
- Plant Stress Responses and Tolerance
- Chemokine receptors and signaling
- Mosquito-borne diseases and control
- Immune Response and Inflammation
- RNA Research and Splicing
- Toxin Mechanisms and Immunotoxins
- Viral Infections and Vectors
University of Pennsylvania
2022-2025
Johns Hopkins University
2013-2024
Johns Hopkins Medicine
2014-2024
Harvard University
2015
University of Washington
1999-2015
Stanford Health Care
2015
Portland State University
1999
University of South Carolina
1999
Southwest Minnesota State University
1999
Ball State University
1999
Abstract Pathways that control, or can be exploited to alter, the increase in airway smooth muscle (ASM) mass and cellular remodeling occur asthma are not well defined. Here we report expression of odorant receptors (ORs) belonging superfamily G-protein coupled (GPCRs), as canonical olfaction machinery (G olf AC3) human bronchi. In primary cultures isolated ASM, identified mRNA for multiple ORs. Strikingly, OR51E2 was most highly enriched OR transcript mapped olfactome lung-resident cells. a...
Hematopoietic stem cell transplantation (HSCT) can replace endogenous microglia with circulation-derived macrophages but has high mortality. To mitigate the risks of HSCT and expand potential for replacement, we engineered an inhibitor-resistant CSF1R that enables robust replacement. A glycine to alanine substitution at position 795 human (G795A) confers resistance multiple inhibitors, including PLX3397 PLX5622. Biochemical cell-based assays show no discernable gain or loss function. G795A-...
Blood-CNS barrier disruption is a hallmark of numerous neurological disorders, yet whether breakdown sufficient to trigger neurodegenerative disease remains unresolved. Therapeutic strategies mitigate hyperpermeability are also limited. Dominant missense mutations the cation channel transient receptor potential vanilloid 4 (TRPV4) cause forms hereditary motor neuron disease. To gain insights into cellular basis these we generated knock-in mouse models TRPV4 channelopathy by introducing two...
Abstract The cation channel transient receptor potential vanilloid 4 (TRPV4) is one of the few identified ion channels that can directly cause inherited neurodegeneration syndromes, but molecular mechanisms are unknown. Here, we show in vivo expression a neuropathy-causing TRPV4 mutant (TRPV4 R269C ) causes dose-dependent neuronal dysfunction and axonal degeneration, which rescued by genetic or pharmacological blockade activity. triggers increased intracellular Ca 2+ through...
Recent studies have highlighted the important roles that "sensory" receptors (olfactory receptors, taste and orphan "GPR" receptors) play in a variety of tissues, including kidney. Although several identified individual sensory kidney, there has not been systematic analysis renal repertoire receptors. In this study, we identify novel belonging to GPR (n = 76), olfactory receptor 6), 11) gene families. A reverse transcriptase (RT)- PCR screening strategies were used which subsequently...
Abstract TRPV4 is a cell surface-expressed calcium-permeable cation channel that mediates cell-specific effects on cellular morphology and function. Dominant missense mutations of cause distinct, tissue-specific diseases, but the pathogenic mechanisms are unknown. Mutations causing peripheral neuropathy localize to intracellular N-terminal domain whereas skeletal dysplasia in multiple domains. Using an unbiased screen, we identified cytoskeletal remodeling GTPase RhoA as interactor....
Microglia, the brain’s resident macrophages, can be reconstituted by surrogate cells - a process termed “microglia replacement.” To expand microglia replacement toolkit, we here introduce estrogen-regulated (ER) homeobox B8 (Hoxb8) conditionally immortalized cell model for generation of immune from murine bone marrow, as versatile replacement. We find that ER-Hoxb8 macrophages are highly comparable to primary marrow-derived (BMD) in vitro, and, when transplanted into microglia-free brain,...
Microglia, the brain’s resident macrophages, can be reconstituted by surrogate cells - a process termed “microglia replacement.” To expand microglia replacement toolkit, we here introduce estrogen-regulated (ER) homeobox B8 (Hoxb8) conditionally immortalized cell model for generation of immune from murine bone marrow, as versatile replacement. We find that ER-Hoxb8 macrophages are highly comparable to primary marrow-derived (BMD) in vitro, and, when transplanted into microglia-free brain,...
To characterize 2 novel TRPV4 mutations in unrelated families exhibiting the Charcot-Marie-Tooth disease type 2C (CMT2C) phenotype.Direct CMT gene testing was performed on with CMT2C. A 4-fold symmetric tetramer model of human generated to map locations these relative previously identified disease-causing (neuropathy, skeletal dysplasia, and osteoarthropathy). Effects expression, localization, channel activity were determined by immunocytochemical, immunoblotting, Ca(2+) imaging,...
Notch signaling is a highly conserved intercellular pathway with tightly regulated and pleiotropic roles in normal tissue development homeostasis. Dysregulated has also been implicated human disease, including multiple forms of cancer, represents an emerging therapeutic target. Successful such therapeutics requires detailed understanding potential on-target toxicities. Here, we identify autosomal dominant mutations the canonical ligand Jagged1 (or JAG1) as cause peripheral nerve disease 2...
Ubiquitin (Ub)-mediated regulation of plasmalemmal ion channel activity canonically occurs via stimulation endocytosis. Whether ubiquitination can modulate by alternative mechanisms remains unknown. Here, we show that the transient receptor potential vanilloid 4 (TRPV4) cation is multiubiquitinated within its cytosolic N-terminal and C-terminal intrinsically disordered regions (IDRs). Mutagenizing select lysine residues to block but not IDR resulted in a marked elevation TRPV4-mediated...
The Aedes aegypti mosquito transmits both dengue virus (DENV) and Zika (ZIKV) . Individuals in endemic areas are at risk for infection with viruses, as well repeated DENV infection. In the presence of anti-DENV antibodies, outcomes secondary range from mild to life threatening. Furthermore, role cross-reactive antibodies on course ZIKV remains unclear. We assessed ability mAbs or polyclonal immunoglobulin isolated after vaccination upregulate type I IFN production by plasmacytoid DCs (pDCs)...
Microglia, the brain's resident macrophages, can be reconstituted by surrogate cells - a process termed "microglia replacement." To expand microglia replacement toolkit, we here introduce estrogen-regulated (ER) homeobox B8 (Hoxb8) conditionally immortalized cell model for generation of immune from murine bone marrow, as versatile replacement. We find that ER-Hoxb8 macrophages are highly comparable to primary marrow-derived (BMD) in vitro, and, when transplanted into microglia-free brain,...
Olfactory receptors (ORs) are chemosensory G Protein Coupled Receptors that comprise the largest mammalian gene family. ORs serve to identify odors in nose, and also act as chemosensors a variety of other tissues. We previously identified 8 renal ORs; here, we undertook directed RT‐PCR screen for 10 (primers were validated using genomic DNA, taking advantage fact lack introns). 4 murine consistently present multiple kidney samples: 31, 746, 1418 1426 (Olfr31, Olfr746, Olfr1418, Olfr1426;...
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