Antonio Di Cristofano, Ph.D.

The main focus of my laboratory is the dissection of the complex array of signals, in the form of hormones, metabolites, and growth factors, that are integrated to govern the growth and maintenance of advanced cancers. We use the thyroid gland as an ideal model system to study the interaction between these signals in normal homeostasis as well as in the context of neoplastic transformation and progression. Additional, parallel work is in the context of Ewing sarcoma.

We utilize genetically engineered mouse models and cell line models to identify and deconstruct the signaling cascades altered during early neoplastic transformation to identify critical signaling nodes and to design and test in vivo innovative, rationally designed therapeutic approaches for advanced cancer

1. Inhibition Of One-Carbon Metabolism In Ewing Sarcoma Results In Profound And Prolonged Growth Suppression Associated With Purine Depletion.
   Zirpoli S, Copperman N, Patel S, Forrest A, Hou Z, Matherly LH, Loeb DM, Di Cristofano A. bioRxiv [Preprint]. 2025 Apr 29:2025.04.13.647987. doi: 10.1101/2025.04.13.647987.PMID: 40376089
2. A zebrafish xenotransplant model of anaplastic thyroid cancer to study tumor microenvironment and innate immune cell interactions in vivo.
   Michael C, Mendonça-Gomes JM, DePaolo CW, Di Cristofano A, de Oliveira S.
   Endocr Relat Cancer. 2024 May 15;31(7):e230195. doi: 10.1530/ERC-23-0195. Print 2024 Jul 1.PMID: 38657656
3. Anaplastic thyroid cancer cells upregulate mitochondrial one-carbon metabolism to meet purine demand, eliciting a critical targetable vulnerability.
   Sugarman AJ, Huynh LD, Shabro A, Di Cristofano A.
   Cancer Lett. 2023 Aug 1;568:216304. doi: 10.1016/j.canlet.2023.216304. Epub 2023 Jul 6.PMID: 37422127
4. Real-time, high-resolution imaging of tumor cells in genetically engineered and orthotopic models of thyroid cancer.
   Shanja-Grabarz X, Coste A, Entenberg D, Di Cristofano A.
   Endocr Relat Cancer. 2020 Oct;27(10):529-539. doi: 10.1530/ERC-20-0295.PMID: 32698130
5. Synergistic repression of thyroid hyperplasia by cyclin C and Pten.
   Jezek J, Wang K, Yan R, Di Cristofano A, Cooper KF, Strich R. 
   J Cell Sci. 2019 Aug 15;132(16):jcs230029. doi: 10.1242/jcs.230029.PMID: 31331961
6. PI3K/mTOR inhibition potentiates and extends palbociclib activity in anaplastic thyroid cancer.
   Wong K, Di Cristofano F, Ranieri M, De Martino D, Di Cristofano A.
   Endocr Relat Cancer. 2019 Apr 1;26(4):425-436. doi: 10.1530/ERC-19-0011. Epub 2019 Jan 1.PMID: 30699064
7. PI3K blockage synergizes with PLK1 inhibition preventing endoreduplication and enhancing apoptosis in anaplastic thyroid cancer.
   De Martino D, Yilmaz E, Orlacchio A, Ranieri M, Zhao K, Di Cristofano A.
   Cancer Lett. 2018 Dec 28;439:56-65. doi: 10.1016/j.canlet.2018.09.024. Epub 2018 Sep 19.PMID: 30243708
8. SGK1 Is a Critical Component of an AKT-Independent Pathway Essential for PI3K-Mediated Tumor Development and Maintenance.
   Orlacchio A, Ranieri M, Brave M, Arciuch VA, Forde T, De Martino D, Anderson KE, Hawkins P, Di Cristofano A.
   Cancer Res. 2017 Dec 15;77(24):6914-6926. doi: 10.1158/0008-5472.CAN-17-2105. Epub 2017 Oct 20.PMID: 29055016
9. Obatoclax kills anaplastic thyroid cancer cells by inducing lysosome neutralization and necrosis.
   Champa D, Orlacchio A, Patel B, Ranieri M, Shemetov AA, Verkhusha VV, Cuervo AM, Di Cristofano A.
   Oncotarget. 2016 Jun 7;7(23):34453-71. doi: 10.18632/oncotarget.9121.PMID: 27144341
10. Obatoclax overcomes resistance to cell death in aggressive thyroid carcinomas by countering Bcl2a1 and Mcl1 overexpression.
    Champa D, Russo MA, Liao XH, Refetoff S, Ghossein RA, Di Cristofano A.
    Endocr Relat Cancer. 2014 Oct;21(5):755-67. doi: 10.1530/ERC-14-0268. Epub 2014 Jul 10.PMID: 25012986