About

The provided page text does not contain a specific professional biography of Professor Ben Z. Stanger. It primarily describes the overall mission, research areas, and achievements of the Abramson Family Cancer Research Institute and mentions several investigators and their contributions, such as Dr. Carl June and Dr. Lewis Chodosh. However, there is no detailed information about Professor Ben Z. Stanger's research focus, background, or key contributions within the provided content.

Research topics

• Biology
• Cancer research
• Genetics
• Bioinformatics
• Cell biology
• Biochemistry
• Sociology
• Computer Science
• Immunology
• Molecular biology
• Internal medicine
• Medicine
• Data science
• Computational biology

Selected publications

• Additional file 9 of Tie2 inhibition disrupts TMEM doorway function and reduces dissemination in pancreatic ductal adenocarcinoma

  Figshare · 2026-05-16

  datasetOpen access

  Supplementary Material 9.

  PublisherDOI

• The HIF-2 transcription factor mediates resistance to ferroptosis in pancreatic cancer

  Molecular Cell · 2026-04-01 · 1 citations

  articleOpen access

  <h2>Summary</h2> Ferroptosis is an iron-dependent form of cell death converging on lipid peroxidation first identified by examining compounds with enhanced lethality to KRAS mutant cells. Despite over 90% of pancreatic ductal adenocarcinoma (PDAC) tumors harboring KRAS mutations, PDAC exhibits relative resistance to ferroptosis compared with other tumor types, and the mechanisms behind this resistance remain unclear. Here, we report that exposure to pancreatic tumor interstitial fluid in synergy with hypoxia induced robust protection against ferroptosis in a manner dependent on the hypoxia-inducible transcription factor 2 (HIF-2). HIF-2 upregulates the expression of both components of the system Xc⁻ cystine transporter and transsulfuration pathway enzymes CBS and CTH to increase intracellular cysteine levels, enabling anti-ferroptotic glutathione production. HIF-2 also induces the Parkin mitophagy factor and suppresses mitochondrial function and reactive oxygen species (ROS) generation. Altogether, our findings uncover an unforeseen role of the HIF-2 transcription factor as a coordinator of anti-ferroptotic mechanisms in pancreatic cancer.

  PublisherDOI

• Sequential platinum and PARP Inhibition enhances PD1 immunotherapy efficacy in murine Brca2 mutated pancreatic cancer

  Scientific Reports · 2026-01-31

  articleOpen access

  Pancreatic ductal adenocarcinoma (PDAC) is a challenging malignancy to treat, but emerging evidence suggests that specific subtypes may respond more favorably to certain therapies. BRCA-mutated PDAC represents a distinct subtype that is particularly sensitive to DNA-damaging therapies. The current standard of care for advanced BRCA-mutated PDAC involves induction platinum-based chemotherapy followed by maintenance therapy with a poly (ADP-ribose) polymerase inhibitor (PARPi). However, the randomized phase III POLO trial, upon which this standard is based, did not demonstrate an improved overall survival in patients who received olaparib compared to those who received placebo, highlighting the need for new therapeutic approaches. Additionally, there is a lack of robust models that recapitulate the tumor microenvironment of BRCA mutated PDAC, limiting the development of next-generation maintenance treatment options. In this study, we developed a syngeneic and immunocompetent mouse model of Brca2-mutated PDAC. The model demonstrated high sensitivity to cisplatin plus gemcitabine, but limited efficacy of PARPi monotherapy. Induction with platinum-based chemotherapy sensitized tumors to PARPi maintenance therapy and promoted an exhausted, T cell-inflamed tumor microenvironment. However, resistance emerged which was associated with CDX2 expression and tumor differentiation. The addition of anti-PD1 treatment to PARPi maintenance enhanced tumor regression and prolonged overall survival. These findings provide preclinical support for ongoing clinical trials investigating immunotherapy with PARPi as a maintenance strategy in homologous recombination-deficient PDAC.

  PublisherOA PDFDOI

• Table S2 from Human Pancreatic Cancer Single-Cell Atlas Reveals Association of CXCL10&lt;sup&gt;+&lt;/sup&gt; Fibroblasts and Basal Subtype Tumor Cells

  2026-01-19

  articleOpen access

  &lt;p&gt;Supplemental Table S2&lt;/p&gt;

  PublisherDOI

• Table S3 from Human Pancreatic Cancer Single-Cell Atlas Reveals Association of CXCL10&lt;sup&gt;+&lt;/sup&gt; Fibroblasts and Basal Subtype Tumor Cells

  2026-01-19

  articleOpen access

  &lt;p&gt;Supplemental Table S3&lt;/p&gt;

  PublisherDOI

• Additional file 5 of Tie2 inhibition disrupts TMEM doorway function and reduces dissemination in pancreatic ductal adenocarcinoma

  Figshare · 2026-05-16

  otherOpen access

  Supplementary Material 5.

  PublisherDOI

• Abstract PR013: Dynamic kinome reprogramming and metabolic rewiring drive adaptive resistance to RAS inhibition in pancreatic cancer

  Cancer Research · 2026-03-05

  article

  Abstract Direct RAS inhibitors are poised to transform the treatment landscape for pancreatic ductal adenocarcinoma (PDAC), where frontline therapy remains cytotoxic chemotherapy with limited clinical benefit. Despite this progress, intrinsic and acquired resistance limit the depth and duration of response. While putative genetic resistance mechanisms explain approximately 50% of cases in non-small cell lung cancer, colorectal cancer, and PDAC, the non-genetic mechanisms driving the remaining 50% remain poorly defined. We utilized transcriptomics, proteomics, and CRISPR-Cas9 genetic screens to elucidate the adaptive programs driving KRAS-independent growth. We identified the activation of distinct transcriptional drivers—MYC, YAP-TEAD, and KEAP1-NRF2—that bypass KRAS inhibition to sustain the resistant state. Comparative RNA-sequencing revealed that MYC- and TEAD-driven networks share substantial overlap with RAS-regulated networks, converging on essential cell cycle and growth genes. In contrast, the KEAP1-NRF2 network operates via a distinct axis characterized by increased dependence on glutamine metabolism. We confirmed the enrichment of these signatures in both preclinical models and patient samples exhibiting resistance to RAS inhibition. We then sought to identify therapeutic strategies to target these resistant states. To identify the upstream signaling governing the YAP/TEAD transcriptional shift, we performed comprehensive phosphoproteomics on PDAC cell lines treated with RAS inhibitors. We observed dynamic kinome reprogramming characterized by the activation of RHO GTPase effector kinases, specifically PAK, ROCK, and PKN. Mechanistically, we demonstrate that pharmacological inhibition of ROCK or PAK decreases nuclear YAP localization and restores sensitivity to RAS inhibition. To identify therapeutic strategies to target NRF2-driven resistance, we leveraged our transcriptomics to identify a metabolic shift with increased reliance on glutamine metabolism. Functionally targeting this metabolic vulnerability with the clinically tractable glutamine antagonists, CB-839/telaglenastat or DRP-104/sirpiglenastat, significantly impaired tumor growth in NRF2-activated models. Collectively, these findings delineate a hierarchy where kinome remodeling drives the transcriptional and metabolic plasticity required for drug tolerance, highlighting the RHO-ROCK-YAP axis and NRF2-regulated glutamine metabolism as actionable targets to extend the durability of next-generation RAS therapies. Citation Format: Clint A. Stalnecker, Wen-Hsuan Chang, Brandon L. Mouery, Ryan D. Mouery, Oluwadara Coker, A. Cole. Edwards, Runying Yang, Crystal L. Pace, Laura E. Herring, Whitney L. Stutts, Joshua H. Choe, Alec J. Vaughan, Timour Baslan, Ben Z. Stanger, Kwok-Kin Wong, Thales Y. Papagiannakopoulos, Andrew J. Aguirre, Joseph D. Mancias, Adrienne D. Cox, Channing J. Der. Dynamic kinome reprogramming and metabolic rewiring drive adaptive resistance to RAS inhibition in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RAS Oncogenesis and Therapeutics; 2026 Mar 5-8; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(5_Suppl_1):Abstract nr PR013.

  PublisherDOI

• Additional file 6 of Tie2 inhibition disrupts TMEM doorway function and reduces dissemination in pancreatic ductal adenocarcinoma

  Figshare · 2026-05-16

  otherOpen access

  Supplementary Material 6.

  PublisherDOI

• Additional file 5 of Tie2 inhibition disrupts TMEM doorway function and reduces dissemination in pancreatic ductal adenocarcinoma

  Figshare · 2026-05-16

  otherOpen access

  Supplementary Material 5.

  PublisherDOI

• Tie2 inhibition disrupts TMEM doorway function and reduces dissemination in pancreatic ductal adenocarcinoma

  Journal of Experimental & Clinical Cancer Research · 2026-05-16

  articleOpen access

  BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic malignancy with limited treatment options. Metastatic dissemination is the principal cause of mortality in PDAC, yet the cellular mechanism by which PDAC tumor cells enter the bloodstream remains unknown. A portal of intravasation is the Tumor Microenvironment of Metastasis (TMEM) doorways. The TMEM doorway is composed of a tumor cell, a Tie2 + macrophage, and endothelial cell, in direct contact triggering a brief, localized vascular opening that permits intravasation. METHODS: We performed time-lapse intravital microscopy in PDAC mouse models to visualize serum extravasation and tumor cell intravasation. TMEM doorway density was quantified using immunohistochemistry of resected human PDAC specimes. TMEM doorway activity was quantified by aligned immunohistochemistry/immunofluorescence of tumor specimens. Mechanistic underpinnings of intravasation were tested using an in vitro intravasation transendothelial migration (iTEM) assay. Tie2 signaling was inhibited in vivo with the Tie2 inhibitor rebastinib (~ 0.44 mg/day in chow for 3 weeks). A macrophage-specific Tie2 conditional knockout mouse was generated to evaluate macrophage Tie2-mediated PDAC dissemination. The therapeutic impact of Tie2 blockade was evaluated in an orthotopic perioperative PDAC model incorporating distal pancreatectomy and perioperative FOLFIRINOX plus rebastinib. Statistical analyses used included Mann-Whitney and Kruskal-Wallis tests for clinicopathologic comparisons, one-way ANOVA with Tukey's post hoc test for iTEM, Student's t-test for two-group comparisons, and Kaplan-Meier survival analysis with log-rank testing. RESULTS: In vivo imaging revealed transient, localized vascular openings spatially linked to TMEM doorways. PDAC tumor cell intravasation was observed at TMEM doorways. TMEM doorways were detectable in human PDAC tissues; higher TMEM density was associated with aggressive pathologic factors and was reduced after neoadjuvant therapy. Tie2 inhibition selectively impaired macrophage-driven vascular opening and reduced TMEM doorway activity, diminished tumor cell transendothelial migration, and lowered disseminated tumor cell burden in vivo. In therapeutic studies, Tie2 inhibition combined with FOLFIRINOX improved survival compared with FOLFIRINOX alone. CONCLUSIONS: Intravasation and dissemination is TMEM doorway mediated in PDAC. TMEM doorway function is mediated by Tie2 signaling. Inhibition of Tie2 pharmacologically and genetically decreases TMEM doorway function and PDAC dissemination. Tie2 inhibition may have therapeutic potential combined with chemotherapy or emerging therapies for PDAC.

  PublisherDOI

Recent grants

• Microphysiological systems for modeling autoimmunity in type 1 diabetes

  NIH · $2.3M · 2019–2024

• Mechanisms of bile duct reprogramming

  NIH · $4.3M · 2009–2021

• NIH Grant UC4DK104196

  NIH · $72k · 2019

• NIH Grant R01CA169123

  NIH · $3.1M · 2018

• NIH Grant R03DK076583

  NIH · $156k · 2010

Frequent coauthors

• Jinyang Li

  University of Hong Kong

  315 shared

• Robert H. Vonderheide

  182 shared

• Robert J. Norgard

  179 shared

• Salina Yuan

  University of Pennsylvania

  143 shared

• Jason R. Pitarresi

  University of Massachusetts Chan Medical School

  116 shared

• Takeshi Katsuda

  UPMC Hillman Cancer Center

  105 shared

• Andrew D. Rhim

  98 shared

• Yogev Sela

  95 shared

Education

• B.S., Life Sciences

  Massachusetts Institute of Technology

  1988

• Ph.D., Genetics

  Harvard Medical School

  1997

• M.D.

  Harvard Medical School

  1997

Awards & honors

• Elected into the National Academy of Medicine