Houghton Lab

Dr. Houghton and staff

Peter Houghton, PhD

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

Our studies aim to understand the mechanisms of cancer initiation in children and use this information to develop more effective and less toxic treatments that will increase the cure rate and improve the quality of life for cancer survivors.

UTHSA Faculty Profile: Peter J. Houghton,, PhD

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 ten years of 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 trials.

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 the 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 the emergence of drug-resistant cells, and to explore the therapeutic value of combining selumetinib (or other 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 leverage 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 studied in each Project shown:

Lab Staff

Abhik-BandyopadhyayAbhik Bandyopadhyay, PhD
Research Scientist/ Animal Technician

Kathy-BondraKathryn Bondra
Research Associate

Vanessa-200x225Vanessa Del Pozo
Animal Technician, Vivarium

EdFavors-200x225Ed Favors
Supervisor, Laboratory – Vivarium

Samson-GhiluSamson Ghilu
Animal Technician – Vivarium

Trevor-HollandTrevor Holland
Research Assistant

Dmytro Kovalskyy, PhDDmytro Kovalskyy, PhD
Research Scientist- Senior

Fuyang-LiFuyang Li
Research Scientist

Andrew-RoblesAndrew Robles, PhD
Research Scientist

Anna-RogojinaAnna Rogojina, PhD
Research Scientist

Featured News

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All news

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 pediatric 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

Recent Publications:

Approaches to identifying drug resistance mechanisms to clinically relevant treatments in childhood rhabdomyosarcoma.Ghilu S, Morton CL, Vaseva AV, Zheng S, Kurmasheva RT, Houghton PJ. Cancer Drug Resist. 2022;5:80-89. doi: 10.20517/cdr.2021.112. Epub 2022 Jan 4. PMID: 35450020

Comprehensive surfaceome profiling to identify and validate novel cell-surface targets in osteosarcoma. Wang Y, Tian X, Zhang W, Zhang Z, Lazcano R, Hingorani P, Roth ME, Gill JD, Harrison DJ, Xu Z, Jusu S, Kannan S, Wang J, Lazar AJ, Earley EJ, Erickson SW, Gelb T, Huxley P, Lahdenranta J, Mudd G, Kurmasheva RT, Houghton P, Smith MA, Kolb EA, Gorlick R. Mol Cancer Ther. 2022 Mar 21:molcanther.0836.2021. doi: 10.1158/1535-7163.MCT-21-0836. Online ahead of print. PMID: 35312779

Comprehensive surfaceome profiling to identify and validate novel cell-surface targets in osteosarcoma. Wang Y, Tian X, Zhang W, Zhang Z, Lazcano R, Hingorani P, Roth ME, Gill JD, Harrison DJ, Xu Z, Jusu S, Kannan S, Wang J, Lazar AJ, Earley EJ, Erickson SW, Gelb T, Huxley P, Lahdenranta J, Mudd G, Kurmasheva RT, Houghton P, Smith MA, Kolb EA, Gorlick R.Mol Cancer Ther. 2022 Mar 21:molcanther.0836.2021. doi: 10.1158/1535-7163.MCT-21-0836. Online ahead of print. PMID: 35312779

Extrarenal Anaplastic Wilms Tumor: A Case Report With Genomic Analysis and Tumor Models.Willis KR, Sathe AA, Xing C, Koduru P, Artunduaga M, Butler EB, Park JY, Kurmasheva RT, Houghton PJ, Chen KS, Rakheja D.J Pediatr Hematol Oncol. 2022 May 1;44(4):147-154. doi: 10.1097/MPH.0000000000002413. Epub 2022 Feb 4. PMID: 35129140

Splice-switching of the insulin receptor pre-mRNA alleviates tumorigenic hallmarks in rhabdomyosarcoma.Khurshid S, Montes M, Comiskey DF Jr, Shane B, Matsa E, Jung F, Brown C, Bid HK, Wang R, Houghton PJ, Roberts R, Rigo F, Chandler D. NPJ Precis Oncol. 2022 Jan 11;6(1):1. doi: 10.1038/s41698-021-00245-5.PMID: 35017650

Single-cell RNA profiling identifies diverse cellular responses to EWSR1/FLI1 downregulation in Ewing sarcoma cells. Khoogar R, Li F, Chen Y, Ignatius M, Lawlor ER, Kitagawa K, Huang TH, Phelps DA, Houghton PJ.Cell Oncol (Dordr). 2022 Feb;45(1):19-40. doi: 10.1007/s13402-021-00640-x. Epub 2022 Jan 7. PMID: 34997546 [ ] 7

Altertoxin II, a Highly Effective and Specific Compound against Ewing Sarcoma.Robles AJ, Dai W, Haldar S, Ma H, Anderson VM, Overacker RD, Risinger AL, Loesgen S, Houghton PJ, Cichewicz RH, Mooberry SL. Cancers (Basel). 2021 Dec 7;13(24):6176. doi: 10.3390/cancers13246176.PMID: 34944795

Surfaceome Profiling of Rhabdomyosarcoma Reveals B7-H3 as a Mediator of Immune Evasion. Lavoie RR, Gargollo PC, Ahmed ME, Kim Y, Baer E, Phelps DA, Charlesworth CM, Madden BJ, Wang L, Houghton PJ, Cheville J, Dong H, Granberg CF, Lucien F.Cancers (Basel). 2021 Sep 9;13(18):4528. doi: 10.3390/cancers13184528.PMID: 34572755

Dihydroartemisinin Inhibits mTORC1 Signaling by Activating the AMPK Pathway in Rhabdomyosarcoma Tumor Cells. Luo J, Odaka Y, Huang Z, Cheng B, Liu W, Li L, Shang C, Zhang C, Wu Y, Luo Y, Yang S, Houghton PJ, Guo X, Huang S.Cells. 2021 Jun 1;10(6):1363. doi: 10.3390/cells10061363.PMID: 34205996

International Consensus on Minimum Preclinical Testing Requirements for the Development of Innovative Therapies For Children and Adolescents with Cancer.

Vassal G, Houghton PJ, Pfister SM, Smith MA, Caron HN, Li XN, Shields DJ, Witt O, Molenaar JJ, Colombetti S, Schüler J, Stancato LF.Mol Cancer Ther. 2021 Aug;20(8):1462-1468. doi: 10.1158/1535-7163.MCT-20-0394. Epub 2021 Jun 9. PMID: 34108262

Developing New Agents for Treatment of Childhood Cancer: Challenges and Opportunities for Preclinical Testing.Ghilu S, Kurmasheva RT, Houghton PJ.J Clin Med. 2021 Apr 4;10(7):1504. doi: 10.3390/jcm10071504.PMID: 33916592 [ ] 1

Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children’s Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force.Pacenta HL, Allen-Rhoades W, Langenau D, Houghton PJ, Keller C, Heske CM, Deel MD, Linardic CM, Shern JF, Stewart E, Turpin B, Harrison DJ, Khan J, Mascarenhas L, Skapek SX, Meyer WH, Hawkins DS, Chen EY, Amatruda JF, Hingorani P, Laetsch TW.J Clin Med. 2021 Apr 1;10(7):1416. doi: 10.3390/jcm10071416.PMID: 33915882.