Ana deCarvalho

decarvalho Name: Ana C. deCarvalho
Area of Expertise: Cancer Biology, translational brain tumor research

Position: Assistant Scientist/Professor
Affiliation: Henry Ford Health System / Wayne State University



Brief Description of Research:
High grade gliomas (HGG) are aggressive tumors typically refractory to therapy. Currently HGG patients have very few FDA-approved treatment options, and few clinical trials open to newly diagnosed tumors. The standard of care is comprised of maximal tumor resection, followed by radiation therapy and treatment with the DNA-alkylating agent temozolomide, with modest efficacy in most cases. Among the leading challenges in treating these tumors are the molecular diversity within the patient population and the dynamic intra-tumor molecular heterogeneity. Taking advantage of the large volume of surgeries and specimens available at the Hermelin Brain Tumor Center (HBTC) at Henry Ford Hospital, I have developed a panel of HGG patient derived cancer stem-like cells/neurospheres and orthotopic xenografts (PDX), representing the molecular diversity encountered in the patient population. These models faithfully retain the somatic genomic alterations of the original tumors. The response of the PDX models to the standard of care also parallels the clinical outcomes, further qualifying them as an appropriate platform for testing new therapeutic strategies. We are currently employing the HGG patient-derived models to understand the molecular basis of resistance to therapy, focusing on the role of extrachromosomal oncogene amplification and DNA repair pathways.
5 Select Publications (trainees underlined):
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)

Shimada K, Reznik E, Stokes ME, Krishnamoorthy L, Bos PH, Song Y, Quartararo CE, Pagano NC, Carpizo DR, deCarvalho AC, Lo DC, Stockwell BR. (2018) Copper-Binding Small Molecule Induces Oxidative Stress and Cell-Cycle Arrest in Glioblastoma-Patient-Derived Cells. Cell Chem Biol. 25 (5):585-594 (PMID: 29576531)

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

Hasselbach LA, Irtenkauf SM, Lemke NW, Nelson KK, Berezovsky AD, Carlton ET, Transou AD, Mikkelsen T, deCarvalho AC (2014). Optimization of high grade glioma cell culture from surgical specimens for use in clinically relevant animal models and 3D immunocytochemistry Journal of Visualized Experiments, 83:e51088 (PMID: 24429465)