A5044403338- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- Genetic factors in colorectal cancer
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Lung Cancer Research Studies
- Chemical Reactions and Isotopes
- Neuropeptides and Animal Physiology
- MicroRNA in disease regulation
- Receptor Mechanisms and Signaling
- Pain Mechanisms and Treatments
- Protein Kinase Regulation and GTPase Signaling
- Microtubule and mitosis dynamics
- PI3K/AKT/mTOR signaling in cancer
- Fibroblast Growth Factor Research
- Cancer Cells and Metastasis
- Genetics, Bioinformatics, and Biomedical Research
- Cancer therapeutics and mechanisms
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Ubiquitin and proteasome pathways
- Neuroscience and Neuropharmacology Research
- Single-cell and spatial transcriptomics
- Multiple Myeloma Research and Treatments
- Cancer-related gene regulation
Stanford University
2018-2023
Stratford University
2022
Translational Genomics Research Institute
2013-2014
Temple University
1987-1991
University of Minnesota
1991
The kinase LKB1 is a critical tumor suppressor in sporadic and familial human cancers, yet the mechanisms by which it suppresses growth remain poorly understood. To investigate tumor-suppressive capacity of four canonical families substrates vivo, we used CRISPR/Cas9-mediated combinatorial genome editing mouse model oncogenic KRAS-driven lung adenocarcinoma. We demonstrate that members SIK family are for constraining development. Histologic gene-expression similarities between LKB1-...
Phagocytosis is a key macrophage function, but how phagocytosis shapes tumor-associated (TAM) phenotypes and heterogeneity in solid tumors remains unclear. Here, we utilized both syngeneic novel autochthonous lung tumor models which neoplastic cells express the fluorophore tdTomato (tdTom) to identify TAMs that have phagocytosed vivo. Phagocytic tdTompos upregulated antigen presentation anti-inflammatory proteins, downregulated classic proinflammatory effectors compared tdTomneg TAMs....
While much evidence implicates substance P (SP), an endogenous neurokinin (NK), as a primary sensory transmitter of acute pain in mammalian spinal cord, its role continuous (tonic) is less clear. Although glutamate co-localized with SP dorsal root ganglion neurons, nociceptive processing uncertain. antagonists NKs and excitatory amino acids (EAAs) have been found to be antinociceptive some assays, they not tested against tonic pain. We hypothesize that: (1) EAAs contribute signaling...
Cancer genotyping has identified a large number of putative tumor suppressor genes. Carcinogenesis is multistep process, but the importance and specific roles many these genes during initiation, growth, progression remain unknown. Here we use multiplexed mouse model oncogenic KRAS-driven lung cancer to quantify impact 48 known on diverse aspects carcinogenesis at an unprecedented scale resolution. We uncover previously understudied functional suppressors that constrain in vivo. Inactivation...
Abstract LKB1 is among the most frequently altered tumor suppressors in lung adenocarcinoma. Inactivation of Lkb1 accelerates growth and progression oncogenic KRAS-driven tumors mouse models. However, molecular mechanisms by which constrains tumorigenesis whether cancer state that stems from deficiency can be reverted remains unknown. To identify processes governed vivo, we generated an allele enables inactivation at initiation subsequent restoration established tumors. Restoration...
Abstract Lung cancer is the leading cause of death worldwide, with lung adenocarcinoma being most common subtype. Many oncogenes and tumor suppressor genes are altered in this type, discovery oncogene mutations has led to development targeted therapies that have improved clinical outcomes. However, a large fraction adenocarcinomas lacks known oncogenes, genesis treatment these oncogene-negative tumors remain enigmatic. Here, we perform iterative vivo functional screens using quantitative...
Abstract Background The outcome of patients with metastatic colorectal carcinoma (mCRC) following first line therapy is poor, median survival less than one year. purpose this study was to identify candidate therapeutically targetable somatic events in mCRC patient samples by whole genome sequencing (WGS), so as obtain targeted treatment strategies for individual patients. Methods Four were recruited, all whom had received > 2 prior regimens. Percutaneous needle biopsies metastases...
The proposition that tonic nociception models are more analogous to clinical pain than traditional acute prompted our previous development of a modified mouse paw formalin test. To discern possible modulatory roles and site(s) action endogenous opioid systems, the receptor-preferring agonists sufentanil (mu), U-50,488H (kappa) [D-Pen2,5]enkephalin (DPDPE, delta) were evaluated for antinociceptive activity in paradigm by systemic (except DPDPE), spinal supraspinal routes. All observations...
Substance P (3 micrograms/kg), neurokinin A (20 B (6 micrograms/kg) and acetylcholine (875 all produced salivation upon i.v. infusion in the anesthetized rat. Against single equivalent agonist doses, atropine (135 micrograms/kg i.v.) blocked both acetylcholine- B-, but not substance P- or A-induced salivation. [D-Pro2,D-Trp7,9]-substance (1 mg/kg i.v.), a putative antagonist, reduced responses to mammalian neurokinins caused 2-fold potentiation of acetylcholine-induced...
ABSTRACT Lung cancer is the leading cause of death worldwide, with lung adenocarcinoma being most common subtype. Many oncogenes and tumor suppressor genes are altered in this type discovery oncogene mutations has led to development targeted therapies that have improved clinical outcomes. However, a large fraction adenocarcinomas lacks known oncogenes, genesis treatment these oncogene-negative tumors remain enigmatic. Here, we perform iterative vivo functional screens using quantitative...
<div>Abstract<p>Lung cancer is the leading cause of death worldwide, with lung adenocarcinoma being most common subtype. Many oncogenes and tumor suppressor genes are altered in this type, discovery oncogene mutations has led to development targeted therapies that have improved clinical outcomes. However, a large fraction adenocarcinomas lacks known oncogenes, genesis treatment these oncogene-negative tumors remain enigmatic. Here, we perform iterative <i>in vivo</i>...