Peter Houghton, Ph.D.
Director - Greehey Children’s Cancer Research Institute
Cancer Pharmacology/Drug development for pediatric solid tumors
The lab focuses on developing novel approaches to the treatment of childhood cancer, with funded projects on childhood sarcoma, low-grade glioma, and developing new in vivo models. Our research focuses on fundamental aspects of tumorigenesis, such as identifying proteins that interact with fusion oncogenes that are essential for tumor cell proliferation and survival, and on understanding proliferative signals that are required for proliferation and survival. For pediatric sarcoma, our focus is on growth factor signaling, and understanding the basis for intrinsic and acquired resistance to inhibitors of insulin-like growth factor signaling. Our studies of childhood glioma focus on tumors with mutated (activated) BRAF signaling and exploiting this defect to develop novel therapeutic approaches to prevent the development of drug resistance. A unifying theme running through all studies is the use of Patient-Derived Xenografts (PDX) where tumors from patients are engrafted into immune-incompetent mice. These models provide clinically relevant tissue to study biologic characteristics and to test new therapeutic approaches. The lab is a member of the Pediatric Preclinical Testing Consortium, supported by the NCI to evaluate novel therapeutics. The lab also has a major effort in developing and molecularly characterizing new PDX models of both leukemias and solid tumors from Hispanic patients in Texas.
Related diseases: Pediatric sarcomas (rhabdomyosarcoma, Ewing sarcoma), low-grade brain tumors (glioma), pediatric cancers of the kidney (atypical teratoid/rhabdoid), and nephroblastoma (Wilms tumor)
Techniques: Contemporary molecular biology techniques, patient-derived xenografts (PDX), single-cell sequencing, CyTOF, cell sorting, FACs, protein purification, mass spectrometry, cell culture.
Research & Grants
Singh M, Leasure JM, Chronowski C, Geier B, Bondra K, Duan W, Hensley LA, Villalona-Calero M, Li N, Vergis AM, Kurmasheva RT, Shen C, Woods G, Sebastian N, Fabian D, Kaplon R, Hammond S, Palanichamy K, Chakravarti A, Houghton PJ. FANCD2 is a potential therapeutic target and biomarker in alveolar rhabdomyosarcoma harboring the PAX3-FOXO1 fusion gene. doi: 10.1158/1078-0432.CCR-13-0556. Epub 2014 Apr 30.PMID: 24787670
Cam M, Bid HK, Xiao L, Zambetti GP, Houghton PJ, Cam H. J. p53/TAp63 and AKT regulate mammalian target of rapamycin complex 1 (mTORC1) signaling through two independent parallel pathways in the presence of DNA damage. Biol Chem. 2014 Feb 14;289(7):4083-94. doi: 10.1074/jbc.M113.530303. Epub 2013 Dec 23.PMID: 24366874
Bid HK, Roberts RD, Cam M, Audino A, Kurmasheva RT, Lin J, Houghton PJ, Cam H. ΔNp63 promotes pediatric neuroblastoma and osteosarcoma by regulating tumor angiogenesis. Cancer Res. 2014 Jan 1;74(1):320-9. doi: 10.1158/0008-5472.CAN-13-0894. Epub 2013 Oct 23.PMID: 24154873
Balkhi MY, Iwenofu OH, Bakkar N, Ladner KJ, Chandler DS, Houghton PJ, London CA, Kraybill W, Perrotti D, Croce CM, Keller C, Guttridge DC. miR-29 acts as a decoy in sarcomas to protect the tumor suppressor A20 mRNA from degradation by HuR.Sci Signal. 2013 Jul 30;6(286):ra63. doi: 10.1126/scisignal.2004177. Erratum in: Sci Signal. 2013 Sep 10;6(292):er6. Balkhi, Mumtaz Y [corrected to Balkhi, M Y]. PMID: 23901138
Shen C, Houghton PJ. The mTOR pathway negatively controls ATM by up-regulating miRNAs. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11869-74. doi: 10.1073/pnas.1220898110. Epub 2013 Jul 1.PMID: 23818585