Tara L. Hogenson
A5024460103- Pancreatic and Hepatic Oncology Research
- Chromatin Remodeling and Cancer
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Mechanisms of cancer metastasis
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Epigenetics and DNA Methylation
- Hedgehog Signaling Pathway Studies
- Cancer-related Molecular Pathways
- Pancreatic function and diabetes
- Pancreatitis Pathology and Treatment
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Advanced Breast Cancer Therapies
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Ubiquitin and proteasome pathways
- Protein Tyrosine Phosphatases
- Neuroendocrine Tumor Research Advances
- Gallbladder and Bile Duct Disorders
- RNA Research and Splicing
- Tumors and Oncological Cases
- Genomic variations and chromosomal abnormalities
- Genetic factors in colorectal cancer
Novel (United States)
2014-2024
Mayo Clinic
2014-2024
WinnMed
2024
Mayo Clinic in Arizona
2013-2023
Novelis (Canada)
2021
BACKGROUNDA patient-derived organoid (PDO) platform may serve as a promising tool for translational cancer research. In this study, we evaluated PDO's ability to predict clinical response gastrointestinal (GI) cancers.METHODSWe generated PDOs from primary and metastatic lesions of patients with GI cancers, including pancreatic ductal adenocarcinoma, colorectal cholangiocarcinoma. We compared PDO the observed donor same treatments.RESULTSWe report an approximately 80% concordance rate between...
Direct blockade of KRAS driver mutations in colorectal cancer (CRC) has been challenging. Targeting SOS1, a guanine nucleotide exchange factor, arisen as an attractive approach for KRAS-mutant CRC. Here, we describe the development novel SOS1 degraders and their activity patient-derived CRC organoids (PDO). The design these proteolysis-targeting chimera was based on crystal structures cereblon SOS1. synthesis used 6- 7-OH groups quinazoline core anchor points to connect lenalidomide. Fifteen...
Adenosquamous cancer of the pancreas (ASCP) is a subtype pancreatic that has worse prognosis and greater metastatic potential than more common ductal adenocarcinoma (PDAC) subtype. To distinguish genomic landscape ASCP identify actionable targets for this lethal cancer, we applied DNA content flow cytometry to series 15 tumor samples including five patient-derived xenografts (PDX). We interrogated purified sorted fractions from these with whole-genome copy-number variant (CNV), whole-exome...
<p>Supplementary Figure 8 shows the expression of GLI target genes in all experimental groups.</p>
<p>Supplementary Figure 1 shows correlation of SNP rs1992901 and GLI2 Transcript Expression.</p>
<p>Supplementary Figure 2 describes the characterization of impact Gli2 overexpression in pancreas development. showing that loss has no on development or survival vivo.</p>
<p>Supplementary Figure 3 shows Gli2 expression in CRG and KCRG mice Gli luciferase activity ΔNGli2-transfected cells.</p>
<p>Supplementary Figure 6 describes RNA-seq shows differential gene expression induced by oncogenic KRAS.</p>
<p>Supplementary Figure 7 shows how oncogenic KRAS modulates GLI target gene expression.</p>
<p>Supplementary Figure 9 shows that Gli2 does not change H3K27Ac enrichment at Ccnd1 promoter downstream of oncogenic KRAS.</p>
<p>Supplementary Figure 5 shows the IHC results looking at CD4 and CD8 expression in KC KCRG mice. The show no difference immune landscape between these mouse models.</p>
<p>Supplementary Figure 10 shows not differences in H3K4me1 enrichment at Ccnd1 promoter mutant KRAS cells.</p>
<p>Supplementary Figure 4 shows the validation of Kras signaling activation and chronic pancreatitis phenotypic examples in KC KCRG mice.</p>
The Hedgehog-regulated transcription factors GLI1 and GLI2 play overlapping roles in development disease; however, the mechanisms underlying their interplay remain elusive. We report for first time that physically functionally interact cancer cells. were shown to co-immunoprecipitate PANC1 pancreatic cells RMS13 rhabdomyosarcoma Mapping analysis demonstrated zinc finger domains of both proteins are required heteromerization. RNAi knockdown either or inhibited expression many...
Abstract It has been challenging to target mutant KRAS (mKRAS) in colorectal cancer (CRC) and other malignancies. Recent efforts have focused on developing inhibitors blocking molecules essential for activity. In this regard, SOS1 inhibition arisen as an attractive approach mKRAS CRC given its role a guanine nucleotide exchange factor GTPase. Here, we demonstrated the translational value of blockade CRC. We used patient‐derived organoids (PDOs) preclinical models evaluate their sensitivity...
Approximately 80% of pancreatic cancer patients suffer from cachexia, and one-third die due to cachexia-related complications such as respiratory failure cardiac arrest. Although there has been considerable research into cachexia mechanisms interventions, are, date, no FDA-approved therapies. A major contributing factor for the lack therapy options could be animal models accurately recapitulate human condition. In this study, we generated an aged model compare progression in young versus...
Germline mutations in CDKN2A, encoding the tumor suppressor p16, are responsible for a large proportion of familial melanoma cases and also increase risk pancreatic cancer. We identified four families through cancer probands that were affected by both cancers. These bore germline missense variant CDKN2A (47T>G), p16-L16R mutant protein associated with high occurrence. Here, we investigated biological significance this variant. When transfected into p16-null cells, was expressed at lower...
Monozygotic twins share an identical DNA sequence but typically display some level of phenotypic discordance. The cause this discordance is often unknown. Two known contributing factors to phenotype are genetics and environment. While the mechanism for genetic effect defined through sequence, expression environmental less defined. With emergence field epigenetics, researchers have begun consider it important factor phenotype. Exposure various has been shown on individual's epigenetic marks...
Genomic testing has increased the quantity of information available to oncologists. Unfortunately, many identified sequence alterations are variants unknown significance (VUSs), which thus limit clinician's ability use these findings inform treatment. We applied a combination in silico prediction and molecular modeling tools laboratory techniques rapidly define actionable VUSs.Exome sequencing was conducted on 308 tumors from various origins. Most single nucleotide within gene coding regions...
<p>Supplementary Figure 6 describes RNA-seq shows differential gene expression induced by oncogenic KRAS.</p>