A5025446338- Drug Transport and Resistance Mechanisms
- RNA Interference and Gene Delivery
- Cancer therapeutics and mechanisms
- DNA and Nucleic Acid Chemistry
- Ferrocene Chemistry and Applications
- Cancer Immunotherapy and Biomarkers
- Glioma Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Histone Deacetylase Inhibitors Research
- Immune cells in cancer
- Protein Degradation and Inhibitors
- Immunotherapy and Immune Responses
- Multiple Myeloma Research and Treatments
- CAR-T cell therapy research
- Metal complexes synthesis and properties
- Cytokine Signaling Pathways and Interactions
- Antibiotics Pharmacokinetics and Efficacy
- Toxin Mechanisms and Immunotoxins
- Acute Lymphoblastic Leukemia research
- Cancer Genomics and Diagnostics
- Research on Leishmaniasis Studies
- Cancer Research and Treatments
- Cell death mechanisms and regulation
- Advanced Breast Cancer Therapies
- Cancer Mechanisms and Therapy
University of California, Los Angeles
2022-2025
Dana-Farber Cancer Institute
2019-2024
Harvard University
2020-2024
UCLA Health
2024
The Ohio State University
2017-2019
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2018
The Ohio State University Wexner Medical Center
2017
Paclitaxel is among the most widely used anticancer drugs and known to cause a dose-limiting peripheral neurotoxicity, initiating mechanisms of which remain unknown. Here, we identified murine solute carrier organic anion–transporting polypeptide B2 (OATP1B2) as mediator paclitaxel-induced neurotoxicity. Additionally, using established tests assess acute chronic found that genetic or pharmacologic knockout OATP1B2 protected mice from mechanically induced allodynia, thermal hyperalgesia,...
Despite decades of effort, the sensitivity patient tumors to individual drugs is often not predictable on basis molecular markers alone. Therefore, unbiased, high-throughput approaches match effective drugs, without requiring a priori hypotheses, are critically needed. Here, we improved upon method that previously reported and developed called dynamic BH3 profiling (HT-DBP). HT-DBP microscopy-based, single-cell resolution assay enables chemical screens hundreds thousands candidate freshly...
Abstract Immune checkpoint inhibitor (ICI) immunotherapy leverages the body’s own immune system to attack cancer cells but leads unwanted autoimmune side effects in up 60% of patients. Such immune-related adverse events (IrAEs) may lead treatment interruption, permanent organ dysfunction, hospitalization, and premature death. Thyroiditis is one most common IrAEs, cause thyroid IrAEs remains unknown. In this study, we use a new, physiologically relevant mouse model ICI-associated autoimmunity...
Abstract In many cancers, mortality is associated with the emergence of relapse multidrug resistance (MDR). Thus far, investigation cancer mechanisms has largely focused on acquired genetic mutations. Using acute myeloid leukemia (AML) patient-derived xenografts (PDX), we systematically elucidated a basis MDR and identified drug sensitivity in relapsed AML. We derived pharmacologic for 22 AML PDX models using dynamic BH3 profiling (DBP), together genomics transcriptomics. vivo resistant...
Abstract Over 50% of GBM cases involve EGFR alterations, yet their impact on the tumor microenvironment (TME) remains unclear. Previous studies suggest overexpression fosters an immunosuppressive TME dominated by tumor-associated macrophages (TAM), which inhibit immune cell infiltration and activity. This "cold" nature contributes to poor responses treatments, including checkpoint blockade (ICB), has shown limited effectiveness compared other malignancies. We hypothesized that alterations...
Signal transducer and activator of transcription 1 (STAT1) mediates interferon gamma signaling which activates the expression various genes related to apoptosis, inflammation, cell cycle angiogenesis. Several experimental clinical studies have investigated role STAT1 in primary tumor growth breast cancer; however, its metastasis remains be determined. To determine cancer metastasis, we analyzed WT or STAT1−/− mice orthotopically implanted with metastatic 4T1.2 cells. Primary development was...
Abstract Improvement in survival has been achieved for children and adolescents with AML but is largely attributed to enhanced supportive care as opposed the development of better treatment regimens. High risk subtypes continue have poor outcomes event free rates <40% despite use high intensity chemotherapy combination hematopoietic stem cell transplant. Here we combine high-throughput screening, intracellular accumulation assays, vivo efficacy studies identify therapeutic strategies...
<p>Supplemental Table 2 shows sample IDs submitted for RNA-seq.</p>
<p>Supplemental Table 4 shows raw baseline BH3 profiling data on matched pre- and post-resistant AML PDX models.</p>
<p>Supplemental Figure 2 shows RNA-seq signature of drug-resistant AML PDX models.</p>
<p>Supplemental Figure 3 shows MDR mechanisms contribute to drug resistance in AML PDX models.</p>
<p>Supplemental Table 3 shows overlapping gene sets contributing to KEGG pathway enrichment between acquired resistant PDX models and relapsed AML patients.</p>
<p>Supplemental Figure 6 shows drug response data in AML patient samples at diagnosis and relapse.</p>
<p>Supplemental Table 1 shows clinical and genetic characteristics for AML PDXs.</p>
<p>Supplemental Table 1 shows clinical and genetic characteristics for AML PDXs.</p>
<p>Supplemental table legends 1-4.</p>
<p>Supplemental Figure 11 shows comparison of leukemia-related genetic mutations in drug-resistant and parental AML PDX models.</p>
<p>Supplemental Figure 8 shows ex vivo DBP profiling in AML PDX models guides generation of drug-resistant PDXs.</p>
<p>Supplemental Figure 12 shows targeted agents cluster by mechanism of action.</p>
<p>Supplemental Figure 9 shows FLT-3 ITD+ AML cell lines and PDX models are sensitive to inhibitors identified by DBP across compartments.</p>
<p>Supplemental Figure 7 shows relapsed or primary refractory AML patients demonstrate reduced ex vivo drug sensitivity compared to diagnosis patients.</p>
<p>Supplemental Figure 1 shows dynamic BH3 profiling of healthy human CD34+ cells.</p>
<p>Supplemental Figure 11 shows comparison of leukemia-related genetic mutations in drug-resistant and parental AML PDX models.</p>