A. Califano

Epigenetic targeting of PGBD5-dependent DNA damage in SMARCB1-deficient sarcomas

The paper identifies ATR as a target for combination EZH2 epigenetic therapy in SMARCB1-deficient sarcomas, showing that EZH2 inhibition promotes DNA damage via PGBD5, and that ATR inhibition enhances therapeutic responses.

NSD2 maintains lineage plasticity and castration-resistance in neuroendocrine prostate cancer

This study identifies NSD2 as a key driver of lineage plasticity and castration-resistance in neuroendocrine prostate cancer, showing its inhibition can restore sensitivity to AR inhibitors.

Ras-dependent activation of BMAL2 regulates hypoxic metabolism in pancreatic cancer

This study identifies BMAL2 as a KRAS-dependent regulator of hypoxic metabolism in pancreatic cancer, showing it stabilizes HIF1A and destabilizes HIF2A under hypoxia.

Tumor Explants Elucidate a Cascade of Paracrine SHH, WNT, and VEGF Signals Driving Pancreatic Cancer Angiosuppression

The paper identifies a paracrine signaling cascade involving SHH, WNT, and VEGF that suppresses angiogenesis in pancreatic cancer using tumor explant models.

Therapeutic modulation of the blood-brain barrier and ischemic stroke by a bioengineered FZD4-selective WNT surrogate

This study develops a bioengineered FZD4-selective WNT surrogate that improves BBB function and reduces ischemic stroke damage in mice.

Single-Cell RNAseq Analysis Reveals Robust Anti-PD-1-Mediated Increase of Immune Infiltrate in Metastatic Castration-Sensitive Prostate Cancer

The paper analyzes single-cell RNAseq data from metastatic castration-sensitive prostate cancer patients treated with anti-PD-1 immunotherapy, showing increased immune infiltrate and identifying therapy-resistant tumor subpopulations and druggable targets.

Case Study of Single-cell Protein Activity Based Drug Prediction for Precision Treatment of Cholangiocarcinoma

The paper develops a single-cell framework to prioritize drugs for cholangiocarcinoma by analyzing subpopulations and validating predictions in patient-derived xenografts.

Systematic Elucidation and Pharmacological Targeting of Tumor-Infiltrating Regulatory T Cell Master Regulators

The paper identifies 17 master regulators of tumor-infiltrating regulatory T cells (TI-Tregs) and shows that targeting TRPS1 reduces tumor growth and enhances PD-1 inhibitor efficacy.

OncoLoop: A network-based precision cancer medicine framework

OncoLoop predicts and validates drug sensitivity in tumors and their models by leveraging perturbational profiles of oncology drugs, showing success in prostate cancer models and patient cohorts.

Identification and validation of a non-genetically encoded vulnerability to XPO1 inhibition in malignant rhabdoid tumors - expanding patient-driven discovery beyond the Nof1.

This study identifies XPO1 activation as a non-genetic vulnerability in malignant rhabdoid tumors using patient-driven discovery and validates selinexor as a potential therapeutic.

Network-based identification and pharmacological targeting of host cell master regulators induced by SARS-CoV-2 infection

This study identifies host cell master regulators affected by SARS-CoV-2 and develops a method to find drugs that reverse their inactivation without harming beneficial immune responses.

A Community Challenge for Pancancer Drug Mechanism of Action Inference from Perturbational Profile Data

The paper hosts a DREAM Challenge to evaluate computational models for predicting drug polypharmacology using perturbational profile data from 32 kinase inhibitors.

Developmental and MAPK-responsive transcription factors drive distinct malignant subtypes and genetic dependencies in pancreatic cancer

The paper identifies three developmental lineages in pancreatic cancer driven by master regulators and shows their association with MAPK activity and therapeutic vulnerabilities.

The transcriptomic response of cells to a drug combination is more than the sum of the responses to the monotherapies

The paper shows that drug combination transcriptional responses are not simply additive and develops a prediction algorithm with 0.84 AUROC for synergistic combinations.

AFF3 and BACH2 are master regulators of metabolic inflexibility, β/α-cell transition, and dedifferentiation in type 2 diabetes

The paper identifies AFF3 and BACH2 as master regulators of metabolic inflexibility, β/α-cell transition, and dedifferentiation in type 2 diabetes using single-cell analysis of human islets.

Unbiased Assessment of H-STS cells as high-fidelity models for gastro-enteropancreatic neuroendocrine tumor drug mechanism of action analysis

The paper assesses H-STS cells as models for drug mechanism analysis in gastro-enteropancreatic neuroendocrine tumors using molecular criteria rather than histological features.