A5030495022- interferon and immune responses
- Influenza Virus Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- CAR-T cell therapy research
- Viral gastroenteritis research and epidemiology
- Lymphoma Diagnosis and Treatment
- Viral Infections and Outbreaks Research
- SARS-CoV-2 and COVID-19 Research
- HER2/EGFR in Cancer Research
- Acute Lymphoblastic Leukemia research
- Macrophage Migration Inhibitory Factor
- Disaster Response and Management
- NF-κB Signaling Pathways
- Estrogen and related hormone effects
- Endometriosis Research and Treatment
- Animal health and immunology
- Acute Myeloid Leukemia Research
- Plant Virus Research Studies
- Chronic Myeloid Leukemia Treatments
- Viral Infections and Immunology Research
- Hepatitis B Virus Studies
- Cancer-related gene regulation
- Cytokine Signaling Pathways and Interactions
- Nuclear Receptors and Signaling
Loxo Oncology at Lilly (United States)
2024
Sutro Biopharma (United States)
2021-2023
Kineta (United States)
2010-2022
Seattle University
2010
Fred Hutch Cancer Center
2008
University of California, Irvine
2004-2006
ABSTRACT Human papillomavirus (HPV) types from the beta genus (beta-HPVs) have been implicated in development of skin cancer. A potentially important aspect their carcinogenic role is ability E6 protein to degrade proapoptotic family member Bak, which gives cells survive UV damage. However, it unknown if Bak limited certain beta-HPV or whether expression keratinocytes affects other proteins for apoptosis signaling. We tested abilities several representative members beta-HPVs and protect...
ABSTRACT The cellular response to virus infection is initiated when pathogen recognition receptors (PRR) engage viral pathogen-associated molecular patterns (PAMPs). This process results in induction of downstream signaling pathways that activate the transcription factor interferon regulatory 3 (IRF3). IRF3 plays a critical role antiviral immunity drive expression innate immune genes, including those encoding factors, type 1 interferon, and modulatory cytokines, act concert restrict...
STRO-002 is a novel homogeneous folate receptor alpha (FolRα) targeting antibody-drug conjugate (ADC) currently being investigated in the clinic as treatment for ovarian and endometrial cancers. Here, we describe discovery, optimization, antitumor properties of STRO-002. was generated by conjugation cleavable 3-aminophenyl hemiasterlin linker-warhead (SC239) to nonnatural amino acid para-azidomethyl-L-phenylalanine incorporated at specific positions within high affinity anti-FolRα antibody...
COVID-19 emergency use authorizations and approvals for vaccines were achieved in record time. However, there remains a need to develop additional safe, effective, easy-to-produce, inexpensive prevention reduce the risk of acquiring SARS-CoV-2 infection. This is due difficulties vaccine manufacturing distribution, hesitancy, and, critically, increased prevalence variants with greater contagiousness or reduced sensitivity immunity. Antibodies from eggs hens (immunoglobulin Y; IgY) that...
ABSTRACT Human papillomaviruses (HPVs) belonging to the Betapapillomavirus genus have recently been implicated in squamous cell carcinomas of skin, though mechanisms by which they initiate carcinogenesis are unclear. We show that human foreskin keratinocytes (HFKs) expressing several betapapillomavirus E6 (beta-E6) proteins display life span extension, but not extent seen HFKs HPV type 16 (16E6). Additionally, we demonstrate beta-E6 can differentially activate telomerase. 38E6 exhibit...
Arenaviruses are a significant cause of hemorrhagic fever, an often-fatal disease for which there is no approved antiviral therapy. Lassa fever in particular generates high morbidity and mortality West Africa, where the endemic, recent outbreak Nigeria was larger more geographically diverse than usual. We developing LHF-535, small-molecule viral entry inhibitor that targets arenavirus envelope glycoprotein, as therapeutic candidate other fevers origin. Using lentiviral pseudotype infectivity...
ABSTRACT There is a growing need for novel antiviral therapies that are broad spectrum, effective, and not subject to resistance due viral mutations. Using high-throughput screening methods, including computational docking studies an interferon-stimulated gene 54 (ISG54)-luciferase reporter assay, we identified class of isoflavone compounds act as specific agonists innate immune signaling pathways cause activation the interferon regulatory factor (IRF-3) transcription factor. The activated...
The cellular protein, poly(rC) binding protein 2 (PCBP2), is known to function in picornavirus cap-independent translation. We have further examined the RNA properties and protein–protein interactions of PCBP2 necessary for studied its putative multimerization utilizing yeast two-hybrid assay vitro biochemical methods, including glutathione S-transferase (GST) pull-down assays gel filtration. Through genetic analysis, domain has been localized second K-homologous (KH) between amino acids 125...
LHF-535 is a small-molecule antiviral currently under development as therapeutic option to treat Lassa fever and other viral hemorrhagic fevers of arenavirus origin. The human safety pharmacokinetics were evaluated in two phase 1 trials healthy volunteers.
Abstract Nectin-4 is an immunoglobulin-like antigen overexpressed in a variety of cancers including bladder, breast, NSCLC, and gastric. Normal tissues skin, salivary glands, bladder esophagus express only low to medium levels making the protein attractive target for cancer therapies. The approval enfortumab vedotin-ejfv, anti-Nectin-4 based antibody-drug conjugate (ADC) with microtubule inhibitor payload, either as single agent or combination pembrolizumab has been significant advancement...
Abstract LHF-535 is a small molecule antiviral currently in development for the treatment of Lassa fever, zoonotic disease endemic West Africa that generates significant morbidity and mortality. Current options are inadequate, there no approved therapeutics or vaccines fever. was evaluated lethal guinea pig model pathogenesis, using once-daily administration fixed dose (50 mg/kg/day) initiating either 1 3 days after inoculation with virus. reduced viremia clinical signs protected all animals...
ABSTRACT COVID-19 emergency use authorizations and approvals for vaccines were achieved in record time. However, there remains a need to develop additional safe, effective, easy-to-produce, inexpensive prevention reduce the risk of acquiring SARS-CoV-2 infection. This is due difficulties vaccine manufacturing distribution, hesitancy, and, critically, increased prevalence variants with greater contagiousness or reduced sensitivity immunity. Antibodies from eggs hens (immunoglobulin Y; IgY)...
Abstract Retinoic acid inducible gene I (RIG-I) is essential for directing and priming the host immune response against many RNA viruses. A diverse small molecule library was used in a cell-based screening approach to identify drug-like compounds that could target RIG-I signaling pathway induce downstream IRF3 drive innate antiviral immunity. We identified activate discrete subsets of genes. class hydroxyquinoline activation immunity cultured cells decrease viral load infectious virus...
Abstract Viral sensing by RIG-I and downstream activation of antiviral defenses along with the induction innate immune cytokines is essential from protection against influenza A virus (IAV) infection. We have identified a novel, small-molecule agonist, KIN1148, which binds activates to signal IRF3 response. are developing this molecule as an adjuvant enhance vaccination pandemic H1N1 (pH1N1) IAV. Ex vivo treatment dendritic cells KIN1148 leads their maturation. determined ability suboptimal...
Abstract We have identified a panel of small molecule immunomodulators that activate IRF3 and induce innate immune signaling to drive an antigen-specific protective response against viral infections. Our lead adjuvant candidate, KIN1148, binds retinoic acid inducible gene-I (RIG-I) induces RIG-I activation. Studies using the H1N1 influenza virus challenge model demonstrate immunization with monovalent split vaccine (SV) KIN1148 is dose sparing protects mice lethal A/California/04/2009...