A5029728787- Colorectal Cancer Treatments and Studies
- Lung Cancer Treatments and Mutations
- Cancer, Hypoxia, and Metabolism
- Cancer therapeutics and mechanisms
- Cancer Treatment and Pharmacology
- Medical Imaging Techniques and Applications
- Gastric Cancer Management and Outcomes
- Cancer Cells and Metastasis
- HER2/EGFR in Cancer Research
- Acute Myeloid Leukemia Research
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Epigenetics and DNA Methylation
- Cancer, Stress, Anesthesia, and Immune Response
- Endoplasmic Reticulum Stress and Disease
- Cancer Immunotherapy and Biomarkers
- Single-cell and spatial transcriptomics
- Nanoplatforms for cancer theranostics
- FOXO transcription factor regulation
- Pancreatic function and diabetes
- Antioxidant Activity and Oxidative Stress
- Immune cells in cancer
- Atherosclerosis and Cardiovascular Diseases
- Chronic Myeloid Leukemia Treatments
Memorial Sloan Kettering Cancer Center
1991-2024
Kettering University
2024
Spanish National Cancer Research Centre
2018-2022
Hospital Universitario Virgen de las Nieves
2014
Helmholtz Zentrum München
2012
Ludwig-Maximilians-Universität München
2012
Dana-Farber Cancer Institute
2009
Abstract The most prominent homozygous deletions in cancer affect chromosome 9p21.3 and eliminate CDKN2A/B tumor suppressors, disabling a cell-intrinsic barrier to tumorigenesis. Half of deletions, however, also encompass type I interferon (IFN) gene cluster; the consequences this co-deletion remain unexplored. To functionally dissect other large genomic we developed flexible deletion engineering strategy, MACHETE (molecular alteration chromosomes with engineered tandem elements). Applying...
With the combination of KRASG12C and EGFR inhibitors, KRAS is becoming a druggable target in colorectal cancer. However, secondary resistance limits its efficacy. Using cell lines, patient-derived xenografts, patient samples, we detected heterogeneous pattern putative alterations expected primarily to prevent inhibition ERK signaling by drugs at progression. Serial analysis blood samples on treatment demonstrates that most these are low frequency except for amplification, recurrent mechanism...
Ionizing radiation (IR) can cause gastrointestinal syndrome (GIS), a lethal disorder, by means of unknown mechanisms. We show that high-dose irradiation increases unconventional prefoldin RPB5 interactor (URI) levels in mouse intestinal crypt, but organ regeneration correlates with URI reductions. overexpression intestine protects mice from radiation-induced GIS, whereas halving expression sensitizes to IR. specifically inhibits β-catenin stem cell-like label-retaining (LR) cells, which are...
Intestinal epithelium regenerates rapidly through proliferation of intestinal stem cells (ISCs), orchestrated by potent mitogens secreted within the crypt niche. However, mechanisms regulating these mitogenic factors remain largely unknown. Here, we demonstrate that transit-amplifying (TA) cells, marked unconventional prefoldin RPB5 interactor (URI), control R-spondin production to guide ISC proliferation. Genetic URI ablation in mice injures TA reducing their survival capacity, leading an...
Enteroviruses are suspected to contribute insulin-producing β cell loss and hyperglycemia-induced diabetes. However, mechanisms not fully defined. Here, we show that coxsackievirus B type 4 (CVB4) infection in human islet-engrafted mice rat insulinoma cells displays of unconventional prefoldin RPB5 interactor (URI) PDX1, affecting function identity. Genetic URI ablation the mouse pancreas causes PDX1 depletion cells. Importantly, diabetic heterozygous overexpressing more glucose tolerant....
Perturbations in intermediary metabolism contribute to the pathogenesis of acute myeloid leukemia (AML) and can produce therapeutically actionable dependencies. Here, we probed whether alpha-ketoglutarate (aKG) represents a specific vulnerability AML. Using functional genomics, metabolomics, mouse models, identified aKG dehydrogenase complex, which catalyzes conversion succinyl CoA, as molecular dependency across multiple models adverse-risk Inhibition 2-oxoglutarate (OGDH), E1 subunit...
We describe a mouse model of rectal cancer (RC) involving rapid tumor organoid engraftment via orthotopic transplantation in an immunocompetent setting. This approach uses simple mechanical disruption to allow engraftment, avoiding the use dextran sulfate sodium. The resulting RC tumors invaded from mucosal surface and metastasized distant organs. Histologically, closely resemble human mirror remodeling microenvironment response radiation. murine thus recapitulates key aspects pathogenesis...
Abstract Senescence is a form of stable proliferative arrest that occurs in response to various forms cellular stress. In established cancer, these include unresolved DNA damage triggered by chemotherapeutic agents or irradiation, re-establishment tumor suppressive programs, and drugs target cell cycle progression. Senescent cells take on “Senescence Associated Secretory Phenotype” SASP, characterized increased expression proinflammatory cytokines other factors modulate the tissue...
SUMMARY Somatic chromosomal deletions are prevalent in cancer, yet their functional contributions remain ill-defined. Among the most prominent of these events chromosome 9p21.3, which disable a cell intrinsic barrier to tumorigenesis by eliminating CDKN2A/B tumor suppressor genes. However, half 9p21.3 encompass cluster 16 type I interferons (IFNs) whose co-deletions have not been functionally characterized. To dissect how and other genomic impact we developed MACHETE (Molecular Alteration...
<div>Abstract<p>With the combination of KRAS<sup>G12C</sup> and EGFR inhibitors, KRAS is becoming a druggable target in colorectal cancer. However, secondary resistance limits its efficacy. Using cell lines, patient-derived xenografts, patient samples, we detected heterogeneous pattern putative alterations expected primarily to prevent inhibition ERK signaling by drugs at progression. Serial analysis blood samples on treatment demonstrates that most these are low...
<p>Characterization of acquired resistance in vitro models</p>
<div>Abstract<p>With the combination of KRAS<sup>G12C</sup> and EGFR inhibitors, KRAS is becoming a druggable target in colorectal cancer. However, secondary resistance limits its efficacy. Using cell lines, patient-derived xenografts, patient samples, we detected heterogeneous pattern putative alterations expected primarily to prevent inhibition ERK signaling by drugs at progression. Serial analysis blood samples on treatment demonstrates that most these are low...
<p>C106 resistant cells drug withdrawal and Patient #12 MSK-Impact data</p>
<p>C106 cell lines single sequencing analysis</p>
<p>RW7213 cell lines sequencing analysis</p>
<p>Characterization of acquired resistance in vitro models</p>
<p>Oncoprint of baseline alterations in CRC patients who developed resistance to KRAS G12C and EGFR inhibitors</p>
<p>C106 resistant cells drug withdrawal and Patient #12 MSK-Impact data</p>