Houghton Lab

Peter Houghton, Ph.D.

Dr. Houghton and staff

Director, Greehey Children’s Cancer Research Institute

Rank: Professor
Department: Molecular Medicine
Office: 2.110.12
Tel: 210.562.9056
Email: houghtonp@uthscsa.edu

Our studies are aimed at understanding mechanisms of cancer initiation in children and using this information to develop more effective and less toxic treatments that will increase the cure rate and improve quality of life for cancer survivors.

Lab Research

Research Project A

Signaling pathways in childhood sarcoma

Our earlier studies have identified insulin-like growth factor (IGF) signaling as maintaining proliferation of sarcoma cells, and to be involved in angiogenesis by regulating vascular endothelial cell response to VEGF. The current studies, supported through a Program Project Grant from NCI, are aimed at identifying mechanisms of resistance to therapeutics that target the IGF-axis. These studies integrate IGF, STAT3 and NFκB signaling pathways in childhood sarcoma models both in vitro and in vivo.

More on Project A 

Research Project B:

The Pediatric Preclinical Consortium (PPTC)

The PPTC builds upon 10 years testing of novel agents against panels of cell lines in vitro and tumor xenografts models in mice that represent childhood solid tumors, brain tumors and acute lymphoblastic leukemias. Over 80 drugs or drug combinations have been tested in 83 models of childhood cancer (kidney cancers, sarcomas, neuroblastoma, brain cancers and acute lymphoblastic leukemia). These studies have identified novel drugs and drug combinations that are now in clinical trial.

More on Project B

Research Project C:

Low-Grade Glioma – Brain tumors

Low-Grade gliomas are ‘driven’ by an activated mutant protein ‘BRAF’. We identified a drug that inhibits a kinase (MEK) downstream in the signaling cascade and causes death of these cancer cells. The drug, selumetinib, has recently completed phase I testing through the Pediatric Brain Tumor Consortium (PBTC), and shows promising activity. This project builds upon our initial work to develop effective therapies that prevent or retard emergence of drug-resistant cells, and to explore the therapeutic value of combining selumetinib (or alternate MEK inhibitors) with radiation therapy.

More on Project C  

Goal

The overall goal of this Program Project Grant is to acquire a comprehensive understanding of the interrelationship between NF-κB, STAT3, and IGF signaling pathways in childhood sarcomas (rhabdomyosarcoma, Ewing sarcoma, osteosarcoma) that can be leveraged to develop novel more effective therapies for treating patients. These goals will be achieved through the combined expertise of the principal investigators in childhood sarcoma biology and pediatric cancer drug development, the incorporation of unique small and large animal models of childhood sarcoma, and the broad interactions between Projects 1-3. The basic premise for the work proposed is that each of the three pathways to be studied is important for sarcoma cell proliferation and survival, but that by virtue of the dynamic nature of cellular signaling, these pathways are interactive and combinatorial inhibition may be essential to achieve maximum therapeutic efficacy. A schematic showing Project interactions and specific pathways to be studied in each Project are shown:

Lab Staff

Ivan Xavier Albino Flores
Graduate Research Assistant

Abhik Bandyopadhyay, Ph.D.
Research Scientist/ Animal Technician

Andra Leman Bates
Graduate Research Assistant

Argentina Becker, Ph.D.
Postdoctoral Fellow

Kathryn Bondra
Research Associate

Vanessa Del Pozo
Animal Technician, Vivarium

Trevor Holland
Research Assistant

Roxanne Khoogar
Postdoctoral Fellow

Dmytro Kovalskyy, Ph.D.
Research Scientist- Senior

Dias Kurmashev, Ph.D.
Bioinformatician

Fuyang Li
Research Scientist

Doris Phelps
Director, Laboratory

Andrew Robles, Ph.D.
Research Scientist

Anna Rogojina, Ph.D.
Research Scientist

Matthew Rotondi, Ph.D.
Postdoctoral Fellow

Terry Shackelford, Ph.D.
Adjunct Faculty

Angelina Vaseva, Ph.D.
Assistant Professor/Research

Review Articles

  • A review of new agents evaluated against pediatric acute lymphoblastic leukemia by the Pediatric Preclinical Testing Program. Jones L, Carol H, Evans K, Richmond J, Houghton PJ, Smith MA, Lock RB.Leukemia. 2016 Nov;30(11):2133-2141. doi: 10.1038/leu.2016.192. Epub 2016 Jul 15. Review.PMID:27416986
  • Identifying novel therapeutic agents using xenograft models of pediatric cancer. Kurmasheva RT, Houghton PJ.Cancer Chemother Pharmacol. 2016 Aug;78(2):221-32. doi: 10.1007/s00280-016-3042-6. Epub 2016 May 18. Review.PMID: 27193096
  • Preclinical Childhood Sarcoma Models: Drug Efficacy Biomarker Identification and Validation. Geier B, Kurmashev D, Kurmasheva RT, Houghton PJ.Front Oncol. 2015 Aug 26;5:193. doi: 0.3389/fonc.2015.00193. eCollection 2015. Review.PMID:26380223
  • Targeting FANCD2 for therapy sensitization. Shen C, Houghton PJ.Oncotarget. 2014 Jun 15;5(11):3426-7. No abstract available. PMID:24913333
  • Rhabdomyosarcoma: current challenges and their implications for developing therapies. Hettmer S, Li Z, Billin AN, Barr FG, Cornelison DD, Ehrlich AR, Guttridge DC, Hayes-Jordan A, Helman LJ, Houghton PJ, Khan J, Langenau DM, Linardic CM, Pal R, Partridge TA, Pavlath GK, Rota R, Schäfer BW, Shipley J, Stillman B, Wexler LH, Wagers AJ, Keller C. Cold Spring Harb Perspect Med. 2014 Nov 3;4(11):a025650. doi: 10.1101/cshperspect.a025650. Review.PMID: 25368019
  • Drug discovery in paediatric oncology: roadblocks to progress. Adamson PC, Houghton PJ, Perilongo G, Pritchard-Jones K.Nat Rev Clin Oncol. 2014 Dec;11(12):732-9. doi: 10.1038/nrclinonc.2014.149. Epub 2014 Sep 16. Review.PMID:25223555
  • Targeting FANCD2 for therapy sensitization. Shen C, Houghton PJ.Oncotarget. 2014 Jun 15;5(11):3426-7. No abstract available. PMID:24913333
  • Regulation of mammalian target of rapamycin complex 1 (mTORC1) by hypoxia: causes and consequences. Cam H, Houghton PJ. Target Oncol. 2011 Jun;6(2):95-102. doi: 10.1007/s11523-011-0173-x. Epub 2011 Apr 16. Review.PMID: 21499767
  • Targeting angiogenesis in childhood sarcomas. Bid HK, Houghton PJ. Sarcoma. 2011;2011:601514. doi: 10.1155/2011/601514. Epub 2010 Dec 9. PMID: 21197468 Everolimus. Houghton PJ. Clin Cancer Res. 2010 Mar 1;16(5):1368-72. doi: 10.1158/1078-0432.CCR-09-1314. Epub 2010 Feb 23. Review.PMID: 20179227