A5057870036- Cytokine Signaling Pathways and Interactions
- Cell death mechanisms and regulation
- Synthesis and biological activity
- Metal complexes synthesis and properties
- Cancer therapeutics and mechanisms
- PI3K/AKT/mTOR signaling in cancer
- DNA Repair Mechanisms
- RNA modifications and cancer
- Synthesis and Reactions of Organic Compounds
- Cancer Genomics and Diagnostics
- Cancer Mechanisms and Therapy
- Computational Drug Discovery Methods
- PARP inhibition in cancer therapy
- Radiation Therapy and Dosimetry
- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Treatments and Mutations
- MicroRNA in disease regulation
- Advanced biosensing and bioanalysis techniques
- Adipokines, Inflammation, and Metabolic Diseases
- Chromosomal and Genetic Variations
- Molecular Biology Techniques and Applications
- Bioactive Compounds and Antitumor Agents
- Bacteriophages and microbial interactions
- ATP Synthase and ATPases Research
Emory University
2015-2025
Cancer Institute (WIA)
2015-2022
Winship Cancer Institute
2014-2021
Emory Healthcare
2015
Zero to Three
2014
Central South University
2013
University of Illinois Urbana-Champaign
2013
Seoul National University
2007
Seoul National University Hospital
2005-2007
A major challenge affecting the outcomes of patients with lung cancer is development acquired radioresistance. However, mechanisms underlying resistance to therapy are not fully understood. Here, we discovered that ionizing radiation induces phosphorylation Janus-associated kinase (JAK)-2 and STAT3 in association increased levels Bcl2/Bcl-XL various human cells. To uncover new mechanism(s) radioresistance cancer, established cell model systems As compared radiosensitive parental cells (i.e.,...
It has been demonstrated that regular exercise improves the quality of life in patients undergoing treatment for lung cancer and associated with reductions cancer-specific mortality colon breast cancer. The direct effects cardiovascular on tumor biology, however, remain unknown. authors evaluated a mouse model adenocarcinoma.Luciferase-tagged A549 adenocarcinoma cells were injected through tail vein nude male mice. Then, mice underwent weekly bioluminescent imaging until tumors clearly...
Lung cancer patients with KRAS mutation(s) have a poor prognosis due in part to the development of resistance currently available therapeutic interventions. Development new class anticancer agents that directly targets may provide more attractive option for treatment KRAS-mutant lung cancer. Here we identified small molecule agonist, KRA-533, binds GTP/GDP-binding pocket KRAS. In vitro GDP/GTP exchange assay reveals KRA-533 activates by preventing cleavage GTP into GDP, leading accumulation...
Abstract Bcl-XL is a major antiapoptotic protein in the Bcl-2 family whose overexpression more widely observed human lung cancer cells than that of Bcl-2, suggesting biologically relevant and therefore better therapeutic target for cancer. Here, we screened small molecules selectively BH3 domain (aa 90–98) binding pocket using UCSF DOCK 6.1 program suite NCI chemical library database. We identified two new inhibitors (BXI-61 BXI-72) exhibit selective toxicity against compared with normal...
DNA double-strand breaks (DSBs) are mainly repaired either by homologous recombination (HR) or nonhomologous end-joining (NHEJ) pathways. Here, we showed that myeloid cell leukemia sequence 1 (Mcl-1) acts as a functional switch in selecting between HR and NHEJ Mcl-1 was cycle-regulated during HR, with its expression peaking S/G2 phase. While endogenous depletion reduced enhanced NHEJ, overexpression resulted net increase over NHEJ. directly interacted the dimeric Ku protein complex via Bcl-2...
Rationale: Bak is a major proapoptotic Bcl2 family member and required molecule for apoptotic cell death.High levels of endogenous were observed in both small lung cancer (SCLC) non-small (NSCLC) lines.Increased expression was correlated with poor prognosis NSCLC patients, suggesting that protein an attractive target therapy.The BH3 domain functions as death to initiate death.Thus, the discovery agonist.Methods: The binding pocket (aa75-88) chosen docking site screening activators using UCSF...
Abstract The exchange of genes between cells is known to play an important physiological and pathological role in many organisms. We show that circulating tumor DNA (ctDNA) facilitates cell-specific gene transfer human cancer explain part the mechanisms behind this phenomenon. As ctDNA migrates into nucleus, genetic information transferred. Cell targeting integration require ERVL, SINE or LINE sequences. Chemically manufactured AluSp MER11C sequences replicated multiple myeloma (MM) cell...
Abstract A rationale exists for pharmacologic manipulation of the serine (S)184 phosphorylation site proapoptotic Bcl2 family member Bax as an anticancer strategy. Here, we report refinement agonist SMBA1 to generate CYD-2-11, which has characteristics a suitable clinical lead compound. CYD-2-11 targeted structural pocket proximal S184 in C-terminal region Bax, directly activating its activity by inducing conformational change enabling formation homooligomers mitochondrial membranes. In...
Mcl-1 is a unique antiapoptotic Bcl2 family protein that functions as gatekeeper in manipulating apoptosis and survival cancer cells. Akt an oncogenic kinase regulates multiple cellular its activity significantly elevated human cancers. Here we discovered cross-talk between promoting lung cell growth. Depletion of endogenous from cells using CRISPR/Cas9 or shRNA decreased activity, leading to suppression growth vitro xenografts. Mechanistically, directly interacted via PEST domain with at...
Multiple myeloma (MM) is a heterogeneous plasma cell malignancy and remains incurable. B-cell lymphoma-2 (BCL2) protein correlates with the survival drug resistance of cells. BH3 mimetics have been developed to disrupt binding between BCL2 its pro-apoptotic family partners for treatment MM, but limited therapeutic efficacy. We recently identified small molecule BDA-366 as BH4 domain antagonist, converting it from an anti-apoptotic into molecule. In this study, we demonstrated that induces...
High-linear energy transfer ionizing radiation, derived from high charge (Z) and (E) (HZE) particles, induces clustered/complex DNA double-strand breaks (DSBs) that include small fragments, which are not repaired by the non-homologous end-joining (NHEJ) pathway. The homologous recombination (HR) repair pathway plays a major role in repairing DSBs induced HZE particles. Mre11 complex (Mre11/Rad50/NBS1)-mediated resection of DSB ends is required step preparing for via HR Here we found...
Patient-derived xenograft (PDX) models for cancer research have recently attracted considerable attention in both the academy and industry (Hidalgo et al., 2014; Wilding Bodmer, 2014). PDX been developed from different tumor types including lung to improve drug development process. These are used pre-clinical evaluation can be predictive results of clinical outcomes because they conserve original characteristics such as heterogeneity, complexity molecular diversity (Kopetz 2012)....
High linear energy transfer (LET) radiation from space heavy charged particles or a heavier ion radiotherapy machine kills more cells than low LET radiation, mainly because high radiation-induced DNA damage is difficult to repair. Relative biological effectiveness (RBE) the ratio of effects generated by radiation. Previously, our group and others demonstrated that cell-killing RBE involved in interference with non-homologous end joining but not homologous recombination This effect...
Space radiation is characterized by high-linear energy transfer (LET) ionizing radiation. The relationships between the early biological effects of space and probability cancer in humans are poorly understood. Bcl2 not only functions as a potent antiapoptotic molecule but also an oncogenic protein that induces DNA replication stress. To test role mechanism high-LET radiation-induced lung carcinogenesis, we created lung-targeting transgenic C57BL/6 mice using CC10 promoter to drive expression...
Abstract A variety of organisms have been shown to altered physiology or developed pathology due gene transfer, but mammals never do so. Here, we show that circulating tumor DNA (ct) can promote cell-specific horizontal transfer (HGT) between human cancer cells and explain the mechanisms behind this phenomenon. Once ctDNA enters host cell, it migrates nucleus integrates into cell’s genome, thereby transferring its genetic information. We determine retrotransposons ERVL, SINE, LINE families...