Ana deCarvalho, Ph.D.
Department
Oncology and Pharmacology
Research interests
- Brain tumor pre-clinical research
- Development of patient derived models
- Experimental therapeutics: mechanisms of resistance and target validation
- Tumor evolution and drivers of plasticity and stemness
Research description
RESEARCH DESCRIPTION
High-grade glioma, the most common and aggressive primary brain tumor in adults, carries a dismal prognosis and resists standard treatments of surgery, radiation, and DNA-alkylating chemotherapy. The Hermelin Brain Tumor Center (HBTC) at Henry Ford Hospital maintains one of the world's largest brain tumor biorepositories and contributed significantly to The Cancer Genome Atlas (TCGA). Harnessing this resource, our team has generated a panel of cancer stem-like cells from freshly resected high-grade gliomas, recapitulating key clinical genomic alterations. These models support in vitro assays and patient-derived orthotopic xenografts (PDX) in mice, fueling a preclinical program that addresses key challenges to better outcomes: interpatient molecular diversity, co-activation of multiple oncogenic pathways, absent predictive biomarkers, and tumor plasticity/evolution.
We are assessing investigational and clinical compounds in these models, correlating responses with pre- and post-treatment multi-omics profiling to uncover biomarkers. By dissecting therapy-driven genomic and phenotypic shifts underlying resistance, we design and validate innovative combination therapies. These efforts in clinically faithful models promise to refine trial designs and enable patient stratification for optimal interventions.
PubMed - my bibliography
https://www.ncbi.nlm.nih.gov/sites/myncbi/1bIT-hyTrLckG/bibliography/43477571/public/?sort=date&direction=ascending
Recent publications
Complete list of published work here.
Selected publications
Berezovsky A, Nuga O, Datta I, Bergman K, Sabedot T, Gurdziel K, Irtenkauf S, Hasselbach L, Meng Y, Mueller C, Petricoin EF-III, Brown S, Purandare N, Aras S, Mikkelsen T, Poisson L, Noushmehr H, Ruden D, deCarvalho AC. Impact of Developmental State, p53 Status, and Interferon Signaling on Glioblastoma Cell Response to Radiation and Temozolomide Treatment (2025) PLoS ONE 20(2): e0315171. https://doi.org/10.1371/journal.pone.0315171
Malta TM, Sabedot TS, Morosini NS, Datta I, Garofano L, Vallentgoed WR, Varn FS, Aldape K, D'Angelo F, Bakas S, Barnholtz-Sloan JS, Gan HK, Hasanain M, Hau AC, Johnson KC, Cazacu S, deCarvalho AC, Khasraw M, Kocakavuk E, Kouwenhoven MCM, Migliozzi S, Niclou SP, Niers JM, Ormond DR, Paek SH, Reifenberger G, Sillevis Smitt PA, Smits M, Stead LF, van den Bent MJ, Van Meir EG, Walenkamp A, Weiss T, Weller M, Westerman BA, Ylstra B, Wesseling P, Lasorella A, French PJ, Poisson LM, Consortium TG, Verhaak RGW, Iavarone A, Noushmehr H. The epigenetic evolution of glioma is determined by the IDH1 mutation status and treatment regimen. (2024) Cancer Res. 84(5):741 – 756. PubMed PMID: 38117484.
Ye LF, Reznik E, Korn JM, Lin F, Yang G, Malesky K, Gao H, Loo A, Pagliarini R, Mikkelsen T, Lo DC, deCarvalho AC*, Stockwell BR (2020)*. Patient-derived glioblastoma cultures as a tool for small-molecule drug discovery. Oncotarget 11(4):443-451 (PMID 32064048) (*) co-corresponding authors.
Snyder J, Poisson LM, Noushmehr H, Castro AV, deCarvalho AC, Robin A, Mukherjee A, Lee I, Walbert T (2019). Clinical and research applications of a brain tumor tissue bank in the age of precision medicine. Personalized Medicine 16(2):145-156 (PMID 30816054)
deCarvalho AC, Kim H, Poisson LM, Winn ME, Mueller C, Cherba D, Koeman J, Seth A, Protopopov A, Felicella M, Zheng S, Multani A, Zhang Y, Zhang J, Nam DH, Petricoin EF, Chin L, Mikkelsen T, Verhaak RGW (2018). Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma. Nat Genet. 50 (5): 708 – 717 (PMID: 29686388)
Irtenkauf SM, Sobiechowski S, Hasselbach LA, Nelson KK, Transou AD, Carlton ET, Mikkelsen T, deCarvalho AC (2017) Optimization of glioblastoma mouse orthotopic xenograft models for translational research. Comparative Medicine 67(4):300-314. (PMID: 28513420)
Berezovsky AD, Poisson LM, Cherba D, Webb CP, Transou AD, Lemke NW, Hong X, Hasselbach LA, Irtenkauf SM, Mikkelsen T, deCarvalho AC. (2014) Sox2 promotes malignancy in glioblastoma by regulating plasticity and astrocytic differentiation. Neoplasia, 16(3):193-206 (PMID: 24726753) COVER ARTICLE
Education/training
PhD (2001), Florida State University, Tallahassee, FLCourses taught
CB7210 Fundamentals of Cancer Biology
CB7240 Principles of Cancer Therapy
CB7300 Epigenomics and Transcriptomics
CB7300 Cancer Genomics and Data Analysis
CB7700 Recent Developments in Cancer Biology
PHC7650_2109_001 Current Topics in Cancer Pharmacology