About

M. Celeste Simon, Ph.D., is a Professor in the Department of Cell and Developmental Biology at the University of Pennsylvania Perelman School of Medicine. Her research focuses on cancer cell metabolism, tumor immunology, metastasis, and responses to oxygen and nutrient deprivation in the tumor microenvironment. Her laboratory studies how vascular insufficiency in solid tumors creates microenvironments with limited oxygen and blood-borne nutrients, triggering complex adaptive responses mediated by molecular mechanisms such as hypoxia-inducible factors (HIF), mTOR signaling, autophagy, and ER stress responses. The overall goal of her research is to elucidate the molecular mechanisms by which changes in oxygen and nutrient availability modulate normal tissue homeostasis and contribute to cancer progression, with particular emphasis on metabolic reprogramming, metastasis, and immune interactions in cancers such as kidney, liver, pancreatic, and soft tissue sarcoma.

Research topics

• Cell biology
• Biology
• Cancer research
• Biochemistry
• Genetics
• Chemistry
• Medicine
• Evolutionary biology
• Computational biology
• Pathology

Selected publications

• Korneales Crosslinking beim Keratokonus: Real-Life-Daten und KRC-Empfehlungen

  Die Ophthalmologie · 2026-03-18

  article
  PublisherDOI

• Additional file 1 of Profiling of rare immune cell populations and integrative analysis identify immune ecotypes in newly diagnosed meningiomas

  Figshare · 2026-03-18

  articleOpen access

  Supplementary Material 1.

  PublisherDOI

• Additional file 1 of Profiling of rare immune cell populations and integrative analysis identify immune ecotypes in newly diagnosed meningiomas

  Figshare · 2026-03-18

  articleOpen access

  Supplementary Material 1.

  PublisherDOI

• Profiling of rare immune cell populations and integrative analysis identify immune ecotypes in newly diagnosed meningiomas

  Acta Neuropathologica Communications · 2026-03-18

  articleOpen access

  Meningiomas (MGMs) are the most common primary intracranial tumors in adults with a substantial subset exhibiting aggressive clinical behavior. Immunotherapy represents a potential alternative treatment option, even though MGMs have traditionally been considered “immunologically cold” tumors. This study explored less characterized immune cell subsets —B cells, natural killer (NK) cells, and granulocytes— and their associations with major immune cell populations as well as their prognostic implications. For this purpose, we performed tissue cytometry analysis in a clinically well-annotated multi-center cohort of 97 newly diagnosed MGMs encompassing all WHO grades (1, 2, 3) and DNA methylation classes (benign, intermediate, malignant). Resulting infiltration data were integrated with previously published data on tumor-associated macrophages (TAMs) and tumor-infiltrating T lymphocytes (TILs) to identify MGM immune ecotypes. Overall, infiltration rates of B cells, NK cells, neutrophils, and eosinophils showed lower frequencies and varied widely across tumors. Notably, we observed significantly lower numbers of B cells in MGM with losses in chromosomal arms 10q and 22q, while lower number of T cells were found in patients with a loss of chromosomal arm 1p. In addition, NK cells and eosinophils were enriched in grade 1 and benign tumors, whereas neutrophils predominated in malignant cases. Despite their relatively low abundance, elevated neutrophil frequencies turned out to be an independent of prognostic factor for poor survival. Importantly, subsequent integration of TAM and TIL data derived from the same patient cohort unraveled five distinct immune ecotypes, each displaying characteristic immune cell infiltration patterns and differential survival outcomes. Altogether, this study provides an expanded overview of various rare immune cell subtypes in MGM and demonstrates their integration into different prognostic immune ecotypes, enabling better stratification in future clinical studies.

  PublisherDOI

• Clinical Significance of Preoperative Serum CEA and CA 19-9 Level in Different Stages of Gastric Cancer.

  PubMed · 2025-07-01

  article

  The aim of this prospective study was to identify any relationship of CEA, CA 19-9 with different stages of carcinoma stomach. The current study was conducted at the Department of General Surgery, Bangabandhu Sheikh Mujib Medical University, Bangladesh from January 2021 to February 2022. In this cross-sectional observational study, 52 patients with histologically established stomach cancer were enrolled. Patient was categorized into two groups (elevated /not elevated CEA and CA19-9 group) after preoperative measurement of CEA and CA19-9 level. About 65.4% of cancers are stage III, 23.1% are stage IV, but stage I tumors account for only 1.9% of all malignancies. In stage I, II, III, IV stomach cancer, CEA increased by 4.3%, 13%, 60.9%, 21.7% and CA19-9 increased by 0.0%, 21.1%, 63.2%, 15.8%. Gastric cancer with raised serum CEA and CA 19-9 level may present as advanced stage. Any extensive surgery in this stage may produce poorer outcome. In GC, CA 19-9 and CEA may be used as monitoring and prognostic tool.

  Publisher

• Author Correction: FBP1 controls liver cancer evolution from senescent MASH hepatocytes

  Nature · 2025-01-31 · 1 citations

  erratumOpen access
  PublisherOA PDFDOI

• Osalmid sensitizes clear cell renal cell carcinoma to navitoclax through a STAT3/BCL-XL pathway

  Cancer Letters · 2025-01-31 · 6 citations

  articleOpen access
  PublisherOA PDFDOI

• Branched chain amino acids and their aberrant metabolism in cancer

  Trends in cancer · 2025-11-20 · 4 citations

  articleSenior author
  PublisherDOI

• Chemoresistance of TP53 mutant acute myeloid leukemia requires the mevalonate byproduct, geranylgeranyl pyrophosphate, for induction of an adaptive stress response

  Leukemia · 2025-07-09 · 9 citations

  articleOpen access

  Abstract Acute myeloid leukemia with mutations in TP53 ( TP53 mut AML) is fatal with a median survival of 6 months. RNA sequencing on purified AML patient samples showed that TP53 mut AML had higher expression of mevalonate pathway genes. Using novel, isogenic TP53 mut AML cell lines and primary samples, we determined that TP53 mut AML resistance to AML chemotherapy cytarabine (AraC) correlated with increased mevalonate pathway activity, a lower induction of reactive oxygen species (ROS), and a mitochondrial response with increased mitochondrial mass and oxidative phosphorylation. Pretreatment with the statin class of mevalonate pathway inhibitors reversed these effects and chemosensitized TP53 mut AML. The geranylgeranyl pyrophosphate (GGPP) branch of the mevalonate pathway was required for TP53 mut AML chemoresistance. In addition to its role in mitochondria biogenesis, we identified a novel function of GGPP in regulating glutathione for management of AraC-induced ROS. However, statins alone were inadequate to fully reverse chemoresistance in vivo and in a retrospective study of 364 TP53 mut AML patients who received chemotherapy concurrently with a statin. Finally, we identified clinical settings and strategies to successfully target the mevalonate pathway, particularly to address the unmet need of TP53 mut AML.

  PublisherOA PDFDOI

• BMAL1 and ARNT enable circadian HIF2α responses in clear cell renal cell carcinoma

  Nature Communications · 2025-07-01 · 7 citations

  articleOpen access

  Circadian disruption enhances cancer risk, and many tumors exhibit disordered circadian gene expression. We show rhythmic gene expression is unexpectedly robust in clear cell renal cell carcinoma (ccRCC). The core circadian transcription factor BMAL1 is closely related to ARNT, and we show that BMAL1-HIF2α regulates a subset of HIF2α target genes in ccRCC cells. Depletion of BMAL1 selectively reduces HIF2α chromatin association and target gene expression and reduces ccRCC growth in culture and in xenografts. Analysis of pre-existing data reveals higher BMAL1 in patient-derived xenografts that are sensitive to growth suppression by a HIF2α antagonist (PT2399). BMAL1-HIF2α is more sensitive than ARNT-HIF2α is to suppression by PT2399, and the effectiveness of PT2399 for suppressing xenograft tumor growth in vivo depends on the time of day at which it is delivered. Together, these findings indicate that an alternate HIF2α heterodimer containing the circadian partner BMAL1 influences HIF2α activity, growth, and sensitivity to HIF2α antagonist drugs in ccRCC cells.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01EY009845

  NIH · $2.3M · 2003

• NIH Grant R01HL066310

  NIH · $6.1M · 2018

• Metabolic Influences on Complex Tumor Neighborhoods

  NIH · $8.5M · 2017–2030

• Radiobiology and Imaging Program

  NIH · $93.0M · 1997–2027

• NIH Grant P01CA104838

  NIH · $23.5M · 2021

Frequent coauthors

• Brian Keith

  430 shared

• Nicolas Skuli

  California University of Pennsylvania

  303 shared

• Ellen Puré

  University of Pennsylvania

  139 shared

• Lijoy K. Mathew

  109 shared

• Romain Riscal

  104 shared

• T.S. Karin Eisinger‐Mathason

  103 shared

• Joseph L. Kissil

  Moffitt Cancer Center

  94 shared

• Freddy Radtke

  Swiss Cancer Center Léman

  91 shared

Labs

• M. Celeste Simon LaboratoryPI

Education

• B.A., Microbiology

  Miami University

  1977

• M.S., Microbiology

  Ohio State University

  1980

• Ph.D., Molecular Biology

  The Rockefeller University

  1985

Awards & honors

• Nuclear speckles regulate functional programs in cancer (202…
• FBA1 is a nonenzymatic safety valve preventing insulin hyper…
• Blocking methionine catabolism induces senescence and confer…
• Gastric Cancer Research Award (2022)
• Cholesterol auxotrophy as a targetable vulnerability in clea…