D. G. Kirsch

Enhancing radiotherapy response via intratumoral injection of the TLR9 agonist CpG to stimulate CD8 T cells in an autochthonous mouse model of sarcoma

This study shows that combining radiotherapy with CpG, a TLR9 agonist, enhances tumor response in a mouse sarcoma model by boosting CD8 T cell activity.

Loss of function of Atrx leads to activation of alternative lengthening of telomeres in a primary mouse model of sarcoma

This study shows that loss of Atrx in a mouse sarcoma model activates the ALT telomere maintenance pathway independently of telomerase, leading to telomere instability and APB formation.

Ataxia-telangiectasia mutated (Atm) disruption sensitizes spatially-directed H3.3K27M/TP53 diffuse midline gliomas to radiation therapy

This study shows that disrupting ATM enhances radiation therapy efficacy in p53-mutant DMGs but not p53-wildtype DMGs using mouse models.

Expression of the CIC-DUX4 fusion oncoprotein mimics human CIC-rearranged sarcoma in genetically engineered mouse models

This study generates genetically engineered mouse models of CIC-DUX4 sarcoma that spontaneously develop tumors and express the fusion protein, validating CIC-DUX4 as a transcriptional activator.

Atrx deletion impairs cGAS-STING signaling and increases response to radiation and oncolytic herpesvirus in sarcoma

This study shows that ATRX deletion in sarcomas increases sensitivity to radiation and oncolytic herpesvirus by impairing cGAS-STING signaling and reducing immune response.

56Fe ion exposure increases the incidence of lung and brain tumors at a similar rate in male and female mice

This study shows that 56Fe ion exposure increases lung and brain tumor incidence similarly in male and female mice, with 56Fe ions causing faster tumor development than X-rays.

p53 promotes revival stem cells in the regenerating intestine after severe radiation injury

Both CD8 and CD4 T cells contribute to immunosurveillance preventing the development of neoantigen-expressing autochthonous sarcomas

This study develops an autochthonous murine sarcoma model and shows that both CD8 and CD4 T cells are required for immunosurveillance against neoantigen-expressing tumors.

p53 and RB Cooperate to Suppress Transposable Elements

This study shows that loss of p53 and RB in mouse cells leads to epigenetic changes and upregulation of transposable elements, suggesting they work together to suppress transposons and prevent tumorigenesis.

Temporary knockdown of p53 during focal limb irradiation increases the development of sarcomas

This study shows that temporarily knocking down p53 during radiation therapy increases the risk of sarcoma development in mice.

Atm loss does not radiosensitize a primary mouse model of Pten-deleted brainstem glioma

This study develops a mouse model of PTEN-mutated brainstem glioma and finds that ATM deletion does not enhance radiation efficacy in this model.

Loss of the chromatin remodeler, ATRX, promotes aggressive features of osteosarcoma with increased NF-κB signaling and integrin receptor binding

This study shows that loss of ATRX in osteosarcoma promotes aggressive tumor features through NF-κB signaling and integrin receptor binding, suggesting new therapeutic targets.

13C tracer analysis identifies extensive recycling of endogenous CO2 in vivo

This study uses 13C tracing to show that endogenous CO2 recycling is significant in vivo, affecting isotopologue distribution and providing insights for metabolic studies.

Tumor genotype dictates radiosensitization after Atm deletion in brainstem gliomas

This study shows that deleting Atm in p53-deficient brainstem gliomas enhances radiosensitivity, while p53 wild-type tumors respond to radiotherapy regardless of Atm status.

Activation of Notch1 drives the development of radiation-induced thymic lymphoma in p53 wild-type mice

This study identifies Notch1 activation as a key driver of radiation-induced thymic lymphoma in p53 wild-type mice through genomic and functional analyses.

The Na+/K+ ATPase Regulates Glycolysis and Modifies Immune metabolism in Tumors

This study shows that Na+/K+ ATPase inhibition via digoxin disrupts glycolysis in tumor and healthy cells, alters immune metabolism, and changes tumor microenvironment composition.

Disruption of oncogenic targeting by ISWI via phosphorylation of a prion-like domain

The paper shows that ionizing radiation disrupts oncogenic interactions between the fusion oncoprotein FUS-CHOP and the chromatin remodeler ISWI via phosphorylation of FUS-CHOP's prion-like domain, explaining radiation sensitivity in myxoid liposarcoma.

A single cell atlas reveals distinct immune landscapes in transplant and primary tumors that determine response or resistance to immunotherapy

The paper compares immune landscapes in transplant and primary tumors after immunotherapy and radiotherapy, finding that transplant tumors respond better due to CD8+ T cell enrichment.

Dietary methionine restriction targets one carbon metabolism in humans and produces broad therapeutic responses in cancer

This study shows that dietary methionine restriction affects one carbon metabolism in humans and produces therapeutic responses in cancer by altering metabolic pathways.

Bridging the translational gap: Implementation of multimodal small animal imaging strategies for tumor burden assessment in a co-clinical trial

The paper develops and validates quantitative imaging protocols for preclinical tumor burden assessment in a co-clinical trial using multimodal small animal imaging.