A5052842636- Cell death mechanisms and regulation
- Mechanisms of cancer metastasis
- Lung Cancer Research Studies
- Melanoma and MAPK Pathways
- Cancer therapeutics and mechanisms
- Graphene and Nanomaterials Applications
- Cancer Mechanisms and Therapy
- Peptidase Inhibition and Analysis
- Cancer Research and Treatments
- RNA Interference and Gene Delivery
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Bone health and treatments
- Cancer, Hypoxia, and Metabolism
- Synthesis and biological activity
- RNA modifications and cancer
- interferon and immune responses
- Advanced biosensing and bioanalysis techniques
- Microtubule and mitosis dynamics
- Lung Cancer Treatments and Mutations
- Bacteriophages and microbial interactions
- Histone Deacetylase Inhibitors Research
- Bone Tumor Diagnosis and Treatments
- Sarcoma Diagnosis and Treatment
- Protist diversity and phylogeny
Johns Hopkins University
2013-2025
University of Baltimore
2012-2025
Johns Hopkins Medicine
2011-2024
Sidney Kimmel Comprehensive Cancer Center
2013-2023
Memorial Sloan Kettering Cancer Center
2014
The Wistar Institute
2013
Molecular Oncology (United States)
2013
Johns Hopkins Hospital
2013
DEVCOM Army Research Laboratory
2011
Small-cell lung cancer (SCLC) is an aggressive malignancy with limited therapeutic options. The dismal prognosis in SCLC part associated upregulation of BCL-2 family anti-apoptotic proteins, including BCL-XL and MCL-1. Unfortunately, the currently available inhibitors except inhibitors, are not clinically relevant because various on-target toxicities. We, therefore, aimed to develop effective safe strategy targeting these proteins DT2216 (our platelet-sparing degrader) AZD8055 (an mTOR...
Overexpression of the antiapoptotic protein Bcl-2 is observed in majority small cell lung cancer (SCLC) cases and associated with resistance to chemotherapy. While targeting hematologic malignancies continues show signs promise, translating BH3 mimetic ABT-737 (or ABT-263; navitoclax) clinic for solid tumors has remained problematic, limited single-agent activity early-phase clinical trials. Here, we used patient-derived xenograft (PDX) models SCLC study demonstrated that responses are short...
Abstract Purpose: Small cell lung cancer (SCLC) is a highly aggressive and deadly malignancy. Two major factors contributing to the high mortality of SCLC are early metastasis rapid development therapy resistance. Recent research suggests upregulation epithelial-mesenchymal transition (EMT) program EMT transcription factor Twist1 correlated with accelerated tumor progression chemoradiation (CRT) resistance in SCLC. However, causal relationship between these aspects biology has not been...
Small cell lung cancer (SCLC) is an aggressive disease with one of the highest case-fatality rates among cancer. The recommended therapy for SCLCs has not changed significantly over past 30 years; new therapeutic approaches are a critical need. TP53 mutated in majority SCLC cases and its loss required transgenic mouse models disease. We synthesized array biodegradable poly(β-amino ester) (PBAE) polymers that self-assemble DNA assayed transfection efficiency p53-mutant H446 line using...
Chordomas are rare primary bone tumors that occur along the neuraxis. Primary treatment is surgery, often followed by radiotherapy. Treatment options for patients with recurrence limited and, notably, there no FDA approved therapeutic agents. Development of has been paucity preclinical model systems. We have established and previously reported initial characterization first patient-derived chordoma xenograft model. In this study, we further characterize demonstrate it continues to resemble...
Abstract Most patients with lung squamous cell carcinoma (LSCC) undergo chemotherapy, radiotherapy, and adjuvant immunotherapy for locally advanced disease. The efficacy of these treatments is still limited because dose-limiting toxicity or locoregional recurrence. New combination approaches targets such as actionable oncogenic drivers are needed to advance treatment options LSCC. Moreover, other chemotherapy-ineligible limited. As such, there a critical need the development selective potent...
Abstract Extra copies of centrosomes are frequently observed in cancer cells. To survive and proliferate, cells have developed strategies to cluster extra-centrosomes form bipolar mitotic spindles. The aim this study was investigate whether centrosome clustering (CC) inhibition (CCi) would preferentially radiosensitize non–small cell lung (NSCLC). Griseofulvin (GF; FDA-approved treatment) inhibits CC, combined with radiation treatment (RT), resulted a significant increase the number NSCLC...
Bisphosphonates are used clinically to treat disorders of calcium metabolism and malignant bone disease known inhibit cancer cell growth, adhesion, invasion. However, clinical use these agents for the treatment extraskeletal is limited because low permeability. We recently described a bisphosphonamidate prodrug strategy efficient intracellular release bisphosphonates, including clodronate (CLO), in non-small lung cells. To evaluate anticancer activity this class across many types, (CLO...
Chordomas are primary bone tumors that arise in the cranial base, mobile spine, and sacrococcygeal region, affecting patients of all ages. Currently, there no approved agents for chordoma patients. Here, we evaluated anti-tumor efficacy small molecule inhibitors target oncogenic pathways chordoma, as single combination, to identify novel therapeutic approaches with greatest translational potential. A panel compounds was screened vivo against patient-derived xenograft (PDX) models potentially...
Background/Aim: Small-cell lung cancer (SCLC) is aggressive and confers poor prognosis. Although SCLC shows more response to chemotherapy than other types of cancer, it difficult cure because its frequent recurrence. New drugs molecular targets need be identified. Materials Methods: We investigated the effect nelfinavir, an HIV protease inhibitor, on cells in preclinical treatment studies using patient-derived xenograft (PDX) mouse models. Results: Nelfinavir inhibited cell proliferation...
Abstract In this study, we investigated the contributions of epithelial-mesenchymal transition (EMT) program to small cell lung cancer (SCLC) tumorigenesis and chemoradiation (CRT) response. SCLC is a highly aggressive deadly neuroendocrine malignancy. Two major factors that contribute high mortality are (1) early metastasis (2) rapid development therapy resistance. Recent research suggests upregulation EMT transcription factor Twist1 correlated with accelerated tumor progression CRT...
Abstract Lung squamous cell carcinoma (LSCC) is the second most prevalent type of lung cancer with no FDA-approved targeted therapies. Platinum-based chemotherapy and immunotherapy remain cornerstone current treatments for advanced LSCC, 5-year survival rate less than 10%. Despite abundant knowledge mutational landscape there a paucity effective Amplification chromosome 3q26 common genomic alteration in LSCC this leads to overexpression oncogenic kinases like TNIK. TNIK amplification occurs...
Abstract Chemoradiation (CRT) is the standard first-line therapy for limited stage small cell lung cancer (LS-SCLC), which characterized by early metastasis, intrinsic-acquired CRT resistance and tumor recurrence. confers a 20-25% 5-year overall survival in patients with LS-SCLC. In this study, we utilized patient-derived xenograft (PDX) models to demonstrate of SCLC identified candidate genes from various PDX that represent majority molecular subtypes (n=4 include SCLC-A SCLC-N subtypes)....
Abstract Non-small cell lung carcinoma (NSCLC) is a major cause of cancer mortality. High expression the epithelial-to-mesenchymal transition transcription factor TWIST1 strongly associated with metastatic cancers and treatment resistance. Additionally, can upregulate O-GlcNAcylation which (1) required to suppress fail-safe programs such as oncogene (KRasG12D)-induced senescence (OIS) accelerate tumorigenesis in primary NSCLC tumors, (2) potential modulator DNA repair/radiation response. To...
<p>Combinations of NCB-0846 with conventional chemotherapeutic agents were either antagonistic or additive.</p>
<p>Short-term TNIK inhibition radiosensitized LSCC cells.</p>
<p>Mechanisms of radiosensitization via TNIK inhibition.</p>
<p>TNIK inhibition promoted micronucleus formation in LSCC cells post-ionizing radiation.</p>
<p>TNIK inhibition altered the cell cycle and promoted death post-IR.</p>
<p>Cisplatin did not affect TNIK inhibition-mediated radiosensitization.</p>
<p>TNIK inhibition induced mitotic catastrophe in TNIKhigh cells.</p>
<p>DNA-PK inhibition enhanced TNIK inhibition-induced radiosensitization.</p>