A5064877683- Pancreatic and Hepatic Oncology Research
- Phagocytosis and Immune Regulation
- Cancer Immunotherapy and Biomarkers
- Glioma Diagnosis and Treatment
- Cancer Research and Treatments
- RNA Research and Splicing
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Cancer Treatment and Pharmacology
- Hepatocellular Carcinoma Treatment and Prognosis
- Pancreatic function and diabetes
- CAR-T cell therapy research
- Advanced Electron Microscopy Techniques and Applications
- RNA and protein synthesis mechanisms
- Cancer, Hypoxia, and Metabolism
- CRISPR and Genetic Engineering
- Endoplasmic Reticulum Stress and Disease
- Pancreatitis Pathology and Treatment
- Hippo pathway signaling and YAP/TAZ
- Genetics and Neurodevelopmental Disorders
- Zebrafish Biomedical Research Applications
- Chemokine receptors and signaling
- Genetics, Aging, and Longevity in Model Organisms
- Genomics, phytochemicals, and oxidative stress
- Genetic factors in colorectal cancer
Purdue University West Lafayette
2015-2022
Children's Cancer Therapy Development Institute
2021-2022
Boston Children's Hospital
2017-2022
Harvard University
2017-2019
Boston Children's Museum
2018
Center for Cancer Research
2017
Liposarcomas (LPSs) are the most common soft-tissue cancer. Because of lack animal models, cellular origin and molecular regulation LPS remain unclear. Here, we report that mice with adipocyte-specific activation Notch signaling (Ad/N1ICD) develop complete penetrance. Lineage tracing confirms adipocyte Ad/N1ICD LPS. The resembles human dedifferentiated in histological appearance, anatomical localization, gene expression signature. Before transformation, adipocytes undergo dedifferentiation...
We hypothesized that basic helix–loop–helix (bHLH) MIST1 (BHLHA15) is a “scaling factor” universally establishes secretory morphology in cells perform regulated secretion. Here, we show targeted deletion of caused dismantling the apparatus diverse exocrine cells. Parietal (PCs), whose function to pump acid into stomach, normally lack and do not Forced expression PCs them expand their apical cytoplasm, rearrange mitochondrial/lysosome trafficking, generate large granules. Mist1 induced cohort...
Polo-like kinase 1 (Plk1) plays an important role in cell-cycle regulation. Recent work has suggested that Plk1 could be a biomarker of gemcitabine response pancreatic ductal adenocarcinoma (PDAC). Although targeting to treat PDAC been attempted clinical trials, the results were not promising, and mechanisms resistance inhibition is poorly understood. In addition, progression requires further elucidation. Here, we showed was associated with poor outcomes patients PDAC. inducible transgenic...
Transcriptional networks that govern secretory cell specialization, including instructing cells to develop a unique cytoarchitecture, amass extensive protein synthesis machinery, and be embodied respond endoplasmic reticulum (ER) stress, remain largely uncharacterized. In this study, we discovered the transcription factor MIST1 (Bhlha15), previously shown essential for cytoskeletal organization activity, also functions as potent ER stress-inducible transcriptional regulator. Genome-wide DNA...
Abstract Occurrence of resistance to olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) approved in ovarian carcinoma, has already been shown clinical settings. Identifying combination treatments sensitize tumor cells and/or overcome olaparib is critical. Polo-like kinase 1 (PLK1), master regulator mitosis, also involved the DNA damage response promoting homologous recombination (HR)-mediated repair and recovery from G2/M checkpoint. We hypothesized that PLK1 inhibition could...
PURPOSE This phase II study evaluated the efficacy and tolerability of onvansertib, a polo-like kinase 1 (PLK1) inhibitor, in combination with fluorouracil, leucovorin, irinotecan (FOLFIRI) + bevacizumab for second-line treatment KRAS -mutant metastatic colorectal cancer (mCRC). PATIENTS AND METHODS multicenter, open-label, single-arm enrolled patients -mutated mCRC previously treated oxaliplatin fluorouracil or without bevacizumab. Patients received onvansertib (15 mg/m 2 once daily on days...
The Wnt/β-catenin signaling pathway has been identified as one of the predominantly upregulated pathways in castration-resistant prostate cancer (CRPC). However, whether targeting β-catenin will prove effective a CRPC treatment remains unknown. Polo-like kinase 1 (Plk1) is critical regulator many cell cycle events, and its level significantly elevated upon castration mice carrying xenograft tumors. Indeed, inhibition Plk1 shown to inhibit tumor growth several vivo studies. Here, we show that...
Gemcitabine is the standard-of-care for chemotherapy in patients with pancreatic adenocarcinoma and it can directly incorporate into DNA or inhibit ribonucleotide reductase to prevent replication and, thus, tumor cell growth. Most tumors, however, develop resistance gemcitabine. Polo-like kinase 1 (Plk1), a critical regulator many cycle events, significantly elevated human cancer. In this study, we show that Plk1 required G1/S transition inhibition of reduces synthesis rate cancer cells....
Acinar cells of the exocrine pancreas are tasked with synthesizing, packaging and secreting vast quantities pro-digestive enzymes to maintain proper metabolic homeostasis for organism. Because synthesis high levels hydrolases is potentially dangerous, prone acute pancreatitis (AP), a disease that targets acinar cells, leading acinar-ductal metaplasia (ADM), inflammation fibrosis—events can transition into earliest stages pancreatic ductal adenocarcinoma. Despite wealth information concerning...
Abstract Diffuse intrinsic pontine glioma (DIPG), a rare pediatric brain tumor, afflicts approximately 350 new patients each year in the United States. DIPG is noted for its lethality, as fewer than 1% of survive to five years. Multiple clinical trials involving chemotherapy, radiotherapy, and/or targeted therapy have all failed improve outcomes. Recently, high-throughput sequencing cohort samples identified potential therapeutic targets, including interleukin 13 receptor subunit alpha 2...
Fibrolamellar carcinoma (FLC) is a primary liver cancer that most commonly arises in adolescents and young adults background of normal tissue has poor prognosis due to lack effective chemotherapeutic agents. The DNAJB1-PRKACA gene fusion (DP) been reported the majority FLC tumors; however, its oncogenic mechanisms remain unclear. Given paucity cellular models, particular tumor cell lines, we hypothesized engineering DP HEK293T cells would provide insight into effects gene. We used...
Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric cancer with unmet clinical need. DIPG invasive in nature, where tumor cells interweave into the fiber nerve tracts of pons making unresectable. Accordingly, novel approaches combating disease are utmost importance and receptor-driven cell invasion context under-researched area. Here, we investigated impact on mediated by PLEXINB1, PLEXINB2, platelet growth factor receptor (PDGFR)α, PDGFRβ, epithelial (EGFR), activin 1...
Abstract Background: Onvansertib (Onv) is an oral, small molecule, selective PLK1 kinase inhibitor that demonstrated clinical activity at tolerated drug exposures in combination with FOLFIRI/Bevacizumab (Bev) the 2nd-line treatment of mutated KRAS (mKRAS) metastatic colorectal cancer (mCRC) (Lenz, JCO, 2022). Here we explored biomarkers response to therapy and their associated biology. Methods: In a Phase 1b/2 study, mKRAS mCRC patients prior exposure oxaliplatin (with or without Bev) were...
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma for which subsets of patients have longstanding unmet clinical needs. For example, children with alveolar rhabdomyosarcoma and metastases at diagnosis will experience only 8% disease-free 5-year survival nonlocalized unresectable recurrent disease. Hence, development novel therapeutic strategies urgently needed to improve outcomes. The Plexin-Semaphorin pathway largely unexplored research. However, emerging interest in...
Abstract Introduction: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare variant of (HCC) that preferentially affects young adults with no underlying liver disease. Overall patient outcome poor due to the lack effective treatment options. Recent studies have shown 400 kb pair deletion resulting in DNJAB1-PRKACA fusion transcript and protein majority FL-HCC tumors. The exact oncogenic mechanism this yet be elucidated. In our previous we had noted upregulation p53 phosphorylated tumor...
<div>Abstract<p>Polo-like kinase 1 (Plk1) plays an important role in cell-cycle regulation. Recent work has suggested that Plk1 could be a biomarker of gemcitabine response pancreatic ductal adenocarcinoma (PDAC). Although targeting to treat PDAC been attempted clinical trials, the results were not promising, and mechanisms resistance inhibition is poorly understood. In addition, progression requires further elucidation. Here, we showed was associated with poor outcomes patients...
Supplementary Figure from Targeting Plk1 Sensitizes Pancreatic Cancer to Immune Checkpoint Therapy