A5028869949- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- Kruppel-like factors research
- Pancreatic function and diabetes
- Phagocytosis and Immune Regulation
- Cancer Cells and Metastasis
- Pancreatitis Pathology and Treatment
- Cancer Immunotherapy and Biomarkers
- Biochemical Analysis and Sensing Techniques
- Histone Deacetylase Inhibitors Research
- Cancer-related gene regulation
- FOXO transcription factor regulation
- Abdominal vascular conditions and treatments
- Radiomics and Machine Learning in Medical Imaging
- Diet, Metabolism, and Disease
- Renal and related cancers
- Hibiscus Plant Research Studies
- Blood properties and coagulation
- Lymphoma Diagnosis and Treatment
- Health and Medical Research Impacts
- Immune cells in cancer
- Wnt/β-catenin signaling in development and cancer
- Pediatric Hepatobiliary Diseases and Treatments
- Single-cell and spatial transcriptomics
Henry Ford Health System
2021-2024
Michigan State University
2024
University of Michigan
2019-2022
LMU Klinikum
2017-2020
Ludwig-Maximilians-Universität München
2017-2020
Michigan Center for Translational Pathology
2020
Klinikum rechts der Isar
2014-2018
Technical University of Munich
2015-2018
München Klinik
2017
Acinar-to-ductal metaplasia (ADM) occurring in cerulein-mediated pancreatitis or oncogenic Kras-driven pancreatic cancer development is accompanied by extensive changes the transcriptional program. In this process, acinar cells shut down expression of specific differentiation genes and re-express usually found embryonic progenitor cells. Previous studies have demonstrated that a loss acinar-specific transcription factors sensitizes towards transformation, ultimately resulting development....
Background and aims Besides well-defined genetic alterations, the dedifferentiation of mature acinar cells is an important prerequisite for pancreatic carcinogenesis. Acinar-specific genes controlling cell homeostasis are extensively downregulated during cancer development; however, underlying mechanisms poorly understood. Now, we devised a novel in vitro strategy to determine genome-wide dynamics epigenetic landscape Design With our carcinogenic sequence, performed global gene expression...
Pancreatic ductal adenocarcinoma (PDA) initiation and progression are accompanied by an immunosuppressive inflammatory response. Here, we evaluated the immunomodulatory role of chemosensory signaling in metaplastic tuft cells (MTCs) analyzing GNAT3, a gustatory pathway G-protein expressed MTCs, during PDA progression.
Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at advanced tumor stages with chemotherapy as the only treatment option. Transcriptomic analysis has defined a classical and basal‑like PDAC subtype, which are regulated by epigenetic modification. The present study aimed to determine if drug‑induced reprogramming of pancreatic cancer cells affects subtype identity chemosensitivity. Classical cell lines PaTu‑S, Capan‑1, Capan‑2, Colo357, PaTu‑T, PANC‑1 MIAPaCa‑2, were treated for...
Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion normal cells into precancerous lesions, to progression carcinoma subtypes associated with aggressiveness and therapeutic response. We discovered that acinar cell differentiation, maintained by transcription factor PDX1, suppresses broad gastric identity in metaplasia, neoplasia, classical subtype PDAC mouse human. identified receptor tyrosine kinase ROR2 as marker metaplasia-like...
Summary Pancreatic ductal adenocarcinoma (PDA) is partly initiated through the transdifferentiation of acinar cells to metaplastic ducts that act as precursors neoplasia and cancer. Tuft are solitary chemosensory not found in normal pancreas but arise metaplasia neoplasia, diminishing neoplastic lesions progress carcinoma. Metaplastic tuft (mTCs) function suppress tumor progression communication with microenvironment, their fate during unknown. To determine mTCs PDA progression, we have...
Pancreatic ductal adenocarcinoma (PDA) is partly initiated through the transdifferentiation of acinar cells to metaplasia, which progresses neoplasia and cancer. Tuft (TCs) are chemosensory not found in normal pancreas but arise cancer precursor lesions diminish during progression carcinoma. These metaplastic TCs (mTCs) suppress tumor communication with microenvironment, their fate unknown. To determine mTCs PDA progression, we created a dual recombinase lineage trace model, wherein...
Abstract Background Hepatoblastoma (HB) and pediatric hepatocellular carcinoma (HCC) are the most common malignant liver tumors in childhood. Both tumor types exhibit genetic epigenetic alterations WNT/β-catenin signaling pathway, which is a key regulator of progenitor cells embryonic development. The demonstrate high rate β-catenin mutations gene expression changes several WNT antagonists. However, role inhibitory factor secreted frizzled-related protein 1 (SFRP1) has not been addressed...
Abstract Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion normal cells into precancerous lesions to progression carcinoma subtypes associated with aggressiveness and therapeutic response. We discovered that acinar cell differentiation, maintained by transcription factor Pdx1, suppresses broad gastric identity in metaplasia, neoplasia, classical subtype PDAC mouse human. have identified receptor tyrosine kinase Ror2 as marker metaplasia...
Abstract Pancreatic Cancer has a 12% 5-year survival rate due to late-stage detection and lack of many chemotherapy or targeted therapy options. TIGIT is an immune checkpoint inhibitor being explored in clinical trials pancreatic cancer the implications its ligand (CD155) promoting evasion. marker T cell exhaustion plays key role inhibition anti-tumor responses. We hypothesize that anti-TIGIT therapy, conjunction with other therapies targeting tumor microenvironment, could reverse...
Abstract Introduction The major driver for pancreatic ductal adenocarcinoma (PDAC) is oncogenic KRAS. However, adult acinar cells, a probable origin of PDAC, are largely refractory to KrasG12D-mediated transformation. With the concomitant loss transcription factors that regulate cell differentiation, such as Pdx1 (Pancreatic and Duodenal Homeobox 1), cells undergo rapid identity switch, known acinar-to-ductal metaplasia (ADM). How cooperates with Kras induce transformation unclear. Methods...
Abstract Study of early pancreas neoplasia in humans had previously been limited by lack available tissue. Recent work our group on deceased donor pancreata identified pancreatic intraepithelial (PanIN) lesions non-diseased organs and defined a transcriptomic signature for the microenvironment these pre-cancerous lesions. Prevalence PanINs healthy human tissue was higher than expected established novel model to expand understanding complex biology precursor Epigenetic changes chromatin...
Abstract Pancreatic ductal adenocarcinoma (PDAC) has a dismal 12% 5-year survival rate (SEER) due to lack of early detection biomarkers and resistance standard therapeutic options (surgery, chemotherapy, radiation). Black African Americans (BAA) have 20% increased incidence PDAC compared those with European Ancestry (EA). TIGIT, an immune checkpoint receptor, is marker T cell exhaustion plays key role in the inhibition anti-tumor responses. Recent studies demonstrated that receptor...
Abstract Introduction: Reprogramming of pancreas cell fate drives development pancreatic ductal adenocarcinoma (PDAC). Acinar cells, the most probable origin cancer, undergo a rapid identity switch towards duct-like phenotype upon KrasG12D expression and when combined with pancreatitis or loss acinar differentiation factors. Metaplastic dysplastic cells are heterogeneous proportion acquiring features reminiscent gastric lineages. While some signatures maintained in classical PDAC subtype,...
e16314 Background: While ground has been gained, pancreatic ductal adenocarcinoma (PDAC) continues to have a low 5-year survival of 13%. This is owed partially lack early detection biomarkers and resistance standard therapeutic options. TIGIT, an immune checkpoint receptor, marker T-cell exhaustion plays key role in the inhibition anti-tumor responses. TIGIT inhibitors are being explored clinical trials PDAC. Here we evaluate expression cohort PDAC patients correlate level intensity with...
By Madison George. Pancreatic ductal adenocarcinoma (PDAC) has a dismal 12% 5-year survival rate (SEER) due to lack of early detection biomarkers and resistance standard therapeutic options (surgery, chemotherapy, radiation).
Abstract Study of early pancreas neoplasia in humans had previously been limited by lack available tissue. Recent work our group on deceased donor pancreata identified pancreatic intraepithelial (PanIN) lesions non-diseased organs and defined a transcriptomic signature for the microenvironment these pre-cancerous lesions. Prevalence PanINs healthy human tissue was higher than expected established novel model to expand understanding complex biology precursor Epigenetic changes chromatin...
Abstract Introduction Reprogramming of pancreas cell fate drives development pancreatic ductal adenocarcinoma (PDAC). Acinar cells, the most probable origin cancer, undergo a rapid identity switch towards duct-like phenotype upon KrasG12D expression and when combined with pancreatitis or loss acinar differentiation factors. Metaplastic neoplastic cells are heterogeneous proportion acquiring features reminiscent gastric lineages. While some signatures maintained in classical PDAC subtype,...
Abstract Pancreatic ductal adenocarcinoma (PDA) is partly initiated through the transdifferentiation of acinar cells to metaplastic ducts that act as precursors neoplasia and cancer. Tuft are solitary chemosensory not found in normal pancreas but arise metaplasia neoplasia, diminishing neoplastic lesions progress carcinoma. Metaplastic tuft (mTCs) function suppress tumor progression communication with microenvironment, their fate during unknown. To determine mTCs PDA progression, we have...
<p>ROR2 is associated with gastric identity.</p>
<p>Ablation of <i>Ror2</i> promotes tissue transformation.</p>