Peter J Houghton

Nationwide Children's Hospital, Columbus, Ohio, United States

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Publications (295)1153.49 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: BackgroundAZD1480 is an ATP competitive inhibitor of Janus kinases 1 and 2 (JAK1, 2) that has been shown to inhibit the growth of solid tumor models. This agent was selected for testing the putative role of JAK/STAT signaling in the standard PPTP solid tumor models.ProceduresAZD1480 was tested against the PPTP in vitro cell line panel at concentrations from 1.0 nM to 10 μM and against the PPTP in vivo solid tumor xenograft panels at (60 mg/kg once daily (SID) × 5) for three consecutive weeks. Additional studies evaluated 5 to 20 mg/kg BID × 5 with SID dosing at 7–30 mg/kg at weekends for three consecutive weeks.ResultsIn vitro the median relative IC50 (rIC50) for the PPTP cell lines was 1.5 µM, with a range from 0.3 µM to 5.9 µM. The two cell lines with rIC50 values of 0.3 µM both had ALK activating genomic alterations. AZD1480 demonstrated statistically significant differences (P < 0.05) in EFS distribution compared to control in 89% of the solid tumor xenografts. AZD1480 induced intermediate (EFS T/C > 2) or high-level growth inhibition in 15 of 30 (50%) solid tumor xenografts. Tumor regressions were observed in three of six Wilms tumor models at doses that induced inhibition of Stat3(Y705) phosphorylation.ConclusionsAZD1480 demonstrated significant tumor growth inhibition against most PPTP solid tumor xenografts, similar to that observed for antiangiogenic agents tested by the PPTP. Tumor regressing activity was noted for Wilms tumor xenografts. Pediatr Blood Cancer 2014;XX:XX–XX. © 2014 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 08/2014; · 2.35 Impact Factor
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    ABSTRACT: Predictive biomarkers are required to identify patients who may benefit from the use of BH3 mimetics such as ABT-263. This study investigated the efficacy of ABT-263 against a panel of patient-derived pediatric acute lymphoblastic leukemia (ALL) xenografts and utilized cell and molecular approaches to identify biomarkers that predict in vivo ABT-263 sensitivity. Experimental Design: The in vivo efficacy of ABT-263 was tested against a panel of 31 patient-derived ALL xenografts comprised of MLL-, BCP- and T-ALL subtypes. Basal gene expression profiles of ALL xenografts were analyzed and confirmed by quantitative RT-PCR, protein expression and BH3 profiling. An in vitro co-culture assay with immortalized human mesenchymal cells was utilized to build a predictive model of in vivo ABT-263 sensitivity. Results: ABT-263 demonstrated impressive activity against pediatric ALL xenografts, with 19 of 31 achieving objective responses. Among BCL2 family members, in vivo ABT-263 sensitivity correlated best with low MCL1 mRNA expression levels. BH3 profiling revealed that resistance to ABT-263 correlated with mitochondrial priming by NOXA peptide, suggesting a functional role for MCL1 protein. Using an in vitro co-culture assay, a predictive model of in vivo ABT-263 sensitivity was built. Testing this model against 11 xenografts predicted in vivo ABT-263 responses with high sensitivity (50%) and specificity (100%). Conclusion: These results highlight the in vivo efficacy of ABT-263 against a broad range of pediatric ALL subtypes and shows that a combination of in vitro functional assays can be used to predict its in vivo efficacy.
    Clinical Cancer Research 06/2014; · 7.84 Impact Factor
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    ABSTRACT: Glembatumumab vedotin is an antibody-auristatin conjugate that targets cells expressing the transmembrane glycoprotein NMB (GPNMB, also known as osteoactivin). It has entered clinical evaluation for adult cancers that express GPNMB, including melanoma and breast cancer.
    Pediatric Blood & Cancer 06/2014; · 2.35 Impact Factor
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    Changxian Shen, Peter J Houghton
    Oncotarget 06/2014; · 6.64 Impact Factor
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    ABSTRACT: mTOR is a new promising oncological target. However, most clinical studies reported only modest antitumor activity during mTOR-targeted monotherapies, including studies in osteosarcomas, emphasizing a need for improvement. We hypothesized that the combination with rationally selected other therapeutic agents may improve response. In this study, we examined the efficacy of the mTOR-inhibitor temsirolimus combined with cisplatin or bevacizumab on the growth of human osteosarcoma xenografts (OS-33 and OS-1) in vivo, incorporating functional imaging techniques and microscopic analyses to unravel mechanisms of response. In both OS-33 and OS-1 models, the activity of temsirolimus was significantly enhanced by the addition of cisplatin (TC) or bevacizumab (TB). Extensive immunohistochemical analysis demonstrated apparent effects on tumor architecture, vasculature, apoptosis and the mTOR-pathway with combined treatments. 18F-FLT-PET scans showed a remarkable decrease in 18F-FLT signal in TC- and TB-treated OS-1 tumors, which was already noticeable after one week of treatment. No baseline uptake was observed in the OS-33 model. Both immunohistochemistry and 18F-FLT-PET demonstrated that responses as determined by caliper measurements underestimated the actual tumor response. Although 18F-FLT-PET could be used for accurate and early response monitoring for temsirolimus-based therapies in the OS-1 model, we could not evaluate OS-33 tumors with this molecular imaging technique. Further research on the value of the use of 18F-FLT-PET in this setting in osteosarcomas is warranted. Overall, these findings urge the further exploration of TC and TB treatment for osteosarcoma (and other cancer) patients. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 04/2014; · 6.20 Impact Factor
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    ABSTRACT: We report results of a phase I trial designed to estimate the maximum tolerated dose (MTD), describe dose-limiting toxicities (DLT), and characterize the pharmacokinetic profile of MK-2206, an AKT inhibitor, in children with refractory or recurrent malignancies. MK-2206 was administered either every other day (Schedule 1), or once a week (Schedule 2) in a 28-day cycle. Dose escalations in increments of ∼30% were independently made in each part using the rolling-six design. Serial pharmacokinetic (PK) studies were obtained. Biological studies include analysis of PI3K/PTEN/AKT-cell signaling pathway in pre and post-therapy in PBMC and in tumors at diagnosis or recurrence. Fifty patients (26 males, median age 12.6 years [range, 3.1-21.9]) with malignant glioma (16), ependymoma (4), hepatocellular carcinoma (3), gliomatosis cereberi (2), or other tumors (22) were enrolled; 40 were fully evaluable for toxicity (Schedule 1, n = 23; Schedule 2, n = 17). Schedule 1 DLTs included: grade 3 dehydration in 1/6 patients at 28 mg/m(2) ; grade 4 hyperglycemia and neutropenia in 1/6 patients at 45 mg/m(2) ; and grade 3 rash in 3/6 patients at dose level 4 (58 mg/m(2) ). Schedule 2 DLTs included: grade 3 alkaline phosphatase in 1/6 patients at 90 mg/m(2) ; grade 3 rash in 1/6 patients at 120 mg/m(2) ; and grade 3 rash in 2/6 patients at 155 mg/m(2) . The recommended pediatric phase 2 dose of MK-2206 is 45 mg/m(2) /dose every other day or 120 mg/m(2) /dose weekly. PK appeared linear over the dose range studied. Pediatr Blood Cancer 2014;9999:1-6. © 2014 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 03/2014; · 2.35 Impact Factor
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    ABSTRACT: Medulloblastoma is the most common type of pediatric brain tumor. Although numerous factors influence patient survival rates, more than 30% of all cases will ultimately be refractory to conventional therapies. Current standards of care are also associated with significant morbidities, giving impetus for the development of new treatments. We have previously shown that oncolytic measles virotherapy is effective against medulloblastoma, leading to significant prolongation of survival and even cures in mouse xenograft models of localized and metastatic disease. Because medulloblastomas are known to be highly vascularized tumors, we reasoned that the addition of angiogenesis inhibitors could further enhance the efficacy of oncolytic measles virotherapy. Toward this end, we have engineered an oncolytic measles virus that express a fusion protein of endostatin and angiostatin, two endogenous and potent inhibitors of angiogenesis. Oncolytic measles viruses encoding human and mouse variants of a secretable endostatin/angiostatin fusion protein were designed and rescued according to established protocols. These viruses, known as MV-hE:A and MV-mE:A respectively, were then evaluated for their anti-angiogenic potential and efficacy against medulloblastoma cell lines and orthotopic mouse models of localized disease. Medulloblastoma cells infected by MV-E:A readily secrete endostatin and angiostatin prior to lysis. The inclusion of the endostatin/angiostatin gene did not negatively impact the measles virus' cytotoxicity against medulloblastoma cells or alter its growth kinetics. Conditioned media obtained from these infected cells was capable of inhibiting multiple angiogenic factors in vitro, significantly reducing endothelial cell tube formation, viability and migration compared to conditioned media derived from cells infected by a control measles virus. Mice that were given a single intratumoral injection of MV-E:A likewise showed reduced numbers of tumor-associated blood vessels and a trend for increased survival compared to mice treated with the control virus. These data suggest that oncolytic measles viruses encoding anti-angiogenic proteins may have therapeutic benefit against medulloblastoma and support ongoing efforts to target angiogenesis in medulloblastoma.
    BMC Cancer 03/2014; 14(1):206. · 3.33 Impact Factor
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    ABSTRACT: PF-03084014, a γ-secretase inhibitor, was tested against the PPTP in vitro cell line panel (1.0 nM to 10 μM) and against the in vivo xenograft panels (administered orally twice daily on Days 1–7 and 15–21). PF-03084014 demonstrated limited in vitro activity, with no cell line achieving ≥50% inhibition. PF-03084014 induced significant differences in EFS distribution in 14 of 35 (40%) solid tumor xenografts, and 1 of 9 ALL xenografts (which lacked a NOTCH1 mutation), but objective responses were not observed. PF-03084014 demonstrated limited single agent activity in vitro and in vivo against the pediatric preclinical models studied. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 03/2014; · 2.35 Impact Factor
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    ABSTRACT: MLN0128 is an investigational small molecule ATP-competitive inhibitor of the serine/threonine kinase mTOR. MLN0128 was tested against the in vitro panel at concentrations ranging from 0.1 nM to 1 μM and against the PPTP in vivo panels at a dose of 1 mg/kg administered orally daily × 28. In vitro the median relative IC50 concentration was 19 nM. In vivo MLN0128 induced significant differences in EFS in 24/31 (77%) solid tumor models, but 0/7 ALL xenografts. The modest activity observed for MLN0128 against the PPTP preclinical models is similar to that previously reported for another TOR kinase inhibitor. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 02/2014; · 2.35 Impact Factor
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    ABSTRACT: Under conditions of DNA damage the mTORC1 complex is inhibited, preventing cell cycle progression, and conserving cellular energy by suppressing translation. We show that suppression of mTORC1 signaling to 4E-BP1 requires the coordinated activity of two tumor suppressors, p53 and p63. In contrast, suppression of S6K1 and ribosomal protein S6 phosphorylation by DNA damage is Akt dependent. We find that loss of either p53, required for induction of Sestrin 1/2 or p63, required for induction of REDD1 and activation of TSC, prevents DNA damage-induced suppression of mTORC1 signaling. These data indicate that negative regulation of cap-dependent translation by mTORC1 inhibition subsequent to DNA damage is abrogated in most human cancers.
    Journal of Biological Chemistry 12/2013; · 4.65 Impact Factor
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    ABSTRACT: Pixantrone, a novel aza-anthracenedione with cytotoxic activity, was tested against the PPTP in vitro panel (3.0 nM to 30.0 μM) and against a limited panel of PPTP Wilms tumors and sarcomas (7.5 mg/kg) administered intravenously using an every 4 day × 3 schedule. In vitro pixantrone showed a median relative IC50 value of 54 nM (range <3 nM to 1.03 μM). In vivo pixantrone induced significant differences in EFS distribution compared to controls in two of eight solid tumor xenografts at dose levels relevant to human drug exposure. A complete response was observed for one Wilms tumor xenograft. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 10/2013; · 2.35 Impact Factor
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    ABSTRACT: The tumor suppressor gene p53 and its family members p63/p73 are critical determinants of tumorigenesis. ΔNp63 is a splice variant of p63 which lacks the N-terminal transactivation domain. It is thought to antagonize p53-, p63- and p73-dependent translation, thus blocking their tumor suppressor activity. In our studies of the pediatric solid tumors neuroblastoma and osteosarcoma, we find overexpression of ΔNp63; however, there is no correlation of ΔNp63 expression with p53 mutation status. Our data suggest that ΔNp63 itself endows cells with a gain of function that leads to malignant transformation, a function independent of any p53 antagonism. Here, we demonstrate that ΔNp63 overexpression, independent of p53, increases secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8), leading to elevated phosphorylation of STAT-3 (Tyr-705). We show that elevated phosphorylation of STAT-3 leads to stabilization of HIF-1α protein, resulting in VEGF secretion. We also show human clinical data suggesting a mechanistic role for ΔNp63 in osteosarcoma metastasis. In summary, our study reveals the mechanism by which ΔNp63, as a master transcription factor, modulates tumor angiogenesis.
    Cancer Research 10/2013; · 8.65 Impact Factor
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    ABSTRACT: The BT-40 low-grade childhood astrocytoma xenograft model expresses mutated BRAFV600E and is highly sensitive to the MEK inhibitor selumetinib (AZD6244). In this study we developed and characterized selumetinib resistance and explored approaches to circumventing the mechanism(s) of acquired resistance. BT-40 xenografts were selected in vivo for selumetinib resistance. Resistant tumors were obtained and characterized, as were tumors that reverted to sensitivity. Characterization included expression-profiling, assessment of MEK signature and compensatory pathways, MEK inhibition, BRAF expression, and cytokine levels. Combination treatment of BT-40/AZD resistant tumors with the MEK inhibitor and a STAT3 inhibitor (LLL12) was assessed. Resistance was unstable, tumors reverting to selumetinib sensitivity when passaged in untreated mice, and MEK was equally inhibited in sensitive and resistant tumors by selumetinib. Drug resistance was associated with an enhanced MEK signature, and increased IL6 and IL8 expression. Selumetinib treatment induced phosphorylation of STAT3(Y705) only in resistant xenografts, and similar results were observed in BRAFV600E astrocytic cell lines intrinsically resistant to selumetinib. Treatment of BT-40 resistant tumors with selumetinib or LLL12 had no significant effect, whereas combined treatment induced complete regressions of BT-40/AZD resistant xenografts. Resistance to selumetinib selected in vivo in BT-40 tumor xenografts was unstable. In resistant tumors selumetinib activated STAT3, and combined treatment with selumetinib and LLL12, induced complete responses in resistant BT-40 tumors. These results suggest dual targeting BRAF(V600E) signaling and STAT3 signaling may be effective in selumetinib-resistant tumors, or may retard or prevent onset of resistance.
    Clinical Cancer Research 10/2013; · 7.84 Impact Factor
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    ABSTRACT: Loss of miR-122 causes chronic steatohepatitis and spontaneous hepatocellular carcinoma. However, the consequence of miR-122 deficiency on genotoxic stress-induced liver pathogenesis has not been explored. Here, we investigated the impact of miR-122 depletion on liver pathobiology by treating liver-specific miR-122 knockout (LKO) mice with the hepatocarcinogen diethylnitrosamine (DEN). At 25 weeks post-DEN injection, all LKO mice developed CK-19-positive hepatobiliary cysts, which correlated with DEN-induced transcriptional activation of Cdc25a mediated through E2f1. Additionally, LKO livers were more fibrotic and vascular, and developed larger microscopic tumors, possibly due to elevation of the Axl oncogene, a receptor tyrosine kinase as a novel target of miR-122, and several protumorigenic miR-122 targets. At 35 weeks following DEN exposure, LKO mice exhibited a higher incidence of macroscopic liver tumors (71%) and cysts (86%) compared to a 21.4% and 0% incidence of tumors and cysts, respectively, in control mice. The tumors in LKO mice were bigger (ninefold, P = 0.015) and predominantly hepatocellular carcinoma, whereas control mice mostly developed hepatocellular adenoma. DEN treatment also reduced survival of LKO mice compared to control mice (P = 0.03). Interestingly, induction of oxidative stress and proinflammatory cytokines in LKO liver shortly after DEN exposure indicates predisposition of a pro-tumorigenic microenvironment. Collectively, miR-122 depletion facilitates cystogenesis and hepatocarcinogenesis in mice on challenge with DEN by up-regulating several genes involved in proliferation, growth factor signaling, neovascularization, and metastasis.
    American Journal Of Pathology 10/2013; · 4.52 Impact Factor
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    Peter J Houghton
    Expert Review of Anti-infective Therapy 10/2013; · 2.07 Impact Factor
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    ABSTRACT: Angiogenesis and metastasis are well recognized as processes fundamental to the development of malignancy. Both processes involve the coordination of multiple cellular and chemical activities through myriad signaling networks, providing a mass of potential targets for therapeutic intervention. This review will focus on one master regulator of cell motility, RAC1, and the existing data with regard to its role in cell motility, including particular roles for tumor angiogenesis and invasion/metastasis. We also emphasize the preclinical investigations carried out with RAC1 inhibitors to evaluate the therapeutic potential of this target. Herein, we explore potential future directions as well as the challenges of targeting RAC1 in the treatment of cancer. Recent insights at the molecular and cellular levels are paving the way for a more directed and detailed approach to target mechanisms of RAC1 regulating angiogenesis and metastasis. Understanding these mechanisms may provide insight into RAC1 signaling components as alternative therapeutic targets for tumor angiogenesis and metastasis. Mol Cancer Ther; 12(10); 1-10. ©2013 AACR.
    Molecular Cancer Therapeutics 09/2013; · 5.60 Impact Factor
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    ABSTRACT: TAK-701 is a humanized antibody that binds hepatocyte growth factor (HGF), thus suppressing c-Met transduced signaling and c-Met dependent proliferation and migration of tumor cells. Six childhood solid tumor xenografts were selected for evaluating TAK-701 based on immunochemical detection of HGF/c-Met autocrine signaling [i.e., pMet(Tyr1349) and HGF positive]. TAK-701 was tested using a dose of 30 mg/kg administered by the intraperitoneal (IP) route twice weekly for 4 weeks. TAK-701 did not induce significant differences in EFS distribution in treated tumors compared to control tumors. Objective responses were not observed in any of the tested solid tumor xenografts. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 09/2013; · 2.35 Impact Factor
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    ABSTRACT: Quisinostat (JNJ-26481585) is a second-generation pyrimidyl-hydroxamic acid histone deacetylase (HDAC) inhibitor with high cellular potency towards Class I and II HDACs. Quisinostat was selected for clinical development as it showed prolonged pharmacodynamic effects in vivo and demonstrated improved single agent antitumoral efficacy compared to other analogs. Quisinostat was tested against the PPTP in vitro panel at concentrations ranging from 1.0 nM to 10 μM and was tested against the PPTP in vivo panels at a dose of 5 mg/kg (solid tumors) or 2.5 mg/kg (ALL models) administered intraperitoneally daily × 21. In vitro quisinostat demonstrated potent cytotoxic activity, with T/C% values approaching 0% for all of the cell lines at the highest concentration tested. The median relative IC50 value for the PPTP cell lines was 2.2 nM (range <1-19 nM). quisinostat induced significant differences in EFS distribution compared to control in 21 of 33 (64%) of the evaluable solid tumor xenografts and in 4 of 8 (50%) of the evaluable ALL xenografts. An objective response was observed in 1 of 33 solid tumor xenografts while for the ALL panel, two xenografts achieved complete response (CR) or maintained CR, and a third ALL xenograft achieved stable disease. Quisinostat demonstrated broad activity in vitro, and retarded growth in the majority of solid tumor xenografts studied. The most consistent in vivo activity signals observed were for the glioblastoma xenografts and T-cell ALL xenografts. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 09/2013; · 2.35 Impact Factor
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    ABSTRACT: Volasertib (BI 6727) is a potent inhibitor of Polo-like kinase 1 (Plk1), that is overexpressed in several childhood cancers and cell lines. Because of its novel mechanism of action, volasertib was evaluated through the PPTP. Volasertib was tested against the PPTP in vitro cell line panel at concentrations from 0.1 nM to 1.0 μM and against the PPTP in vivo xenograft panels administered IV at a dose of 30 mg/kg (solid tumors) or 15 mg/kg (ALL models) using a q7dx3 schedule. In vitro volasertib demonstrated cytotoxic activity, with a median relative IC50 value of 14.1 nM, (range 6.0-135 nM). Volasertib induced significant differences in EFS in 19 of 32 (59%) of the evaluable solid tumor xenografts and in 2 of 4 (50%) of the evaluable ALL xenografts. Volasertib induced tumor growth inhibition meeting criteria for intermediate EFS T/C (>2) activity in 11 of 30 (37%) evaluable solid tumor xenografts, including neuroblastoma (4 of 6) and glioblastoma (2 of 3) panels, and 2 of 4 ALL models. Objective responses (CR's) were observed for 4 of 32 solid tumor (two neuroblastoma, one glioblastoma, and one rhabdomyosarcoma) and one of four ALL xenografts. Volasertib shows potent in vitro activity against the PPTP cell lines with no histotype selectivity. In vivo, volasertib induced regressions in several xenograft models. However, pharmacokinetic data suggest that mice tolerate higher systemic exposure to volasertib than humans, suggesting that the current results may over-estimate potential clinical efficacy against the childhood cancers studied. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 08/2013; · 2.35 Impact Factor
  • Changxian Shen, Peter J Houghton
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    ABSTRACT: The ataxia telangiectasia mutated (ATM) checkpoint is the central surveillance system that maintains genome integrity. We found that in the context of childhood sarcoma, mammalian target of rapamycin (mTOR) signaling suppresses ATM by up-regulating miRNAs targeting ATM. Pharmacological inhibition or genetic down-regulation of the mTOR pathway resulted in increase of ATM mRNA and protein both in mouse sarcoma xenografts and cultured cells. mTOR Complex 1 (mTORC1) suppresses ATM via S6K1/2 signaling pathways. microRNA-18a and microRNA-421, both of which target ATM, are positively controlled by mTOR signaling. Our findings have identified a negative feedback loop for the signaling between ATM and mTOR pathways and suggest that oncogenic growth signals may promote tumorigenesis by dampening the ATM checkpoint.
    Proceedings of the National Academy of Sciences 07/2013; · 9.74 Impact Factor

Publication Stats

7k Citations
1,153.49 Total Impact Points


  • 2010–2014
    • Nationwide Children's Hospital
      Columbus, Ohio, United States
    • Chiba University
      Tiba, Chiba, Japan
  • 2011–2013
    • Texas Tech University Health Sciences Center
      El Paso, Texas, United States
    • Ballarat Cancer Research Centre
      Ballaarat, Victoria, Australia
    • The University of Tennessee Health Science Center
      • Department of Pediatrics
      Memphis, Tennessee, United States
  • 2010–2013
    • The Children's Hospital of Philadelphia
      Philadelphia, Pennsylvania, United States
  • 2009–2013
    • Children's Cancer Institute Australia
      Randwick, New South Wales, Australia
    • Putra University, Malaysia
      • Institute of Bioscience
      Klang, Selangor, Malaysia
    • Children's Hospital Los Angeles
      Los Angeles, California, United States
  • 2003–2013
    • Duke University Medical Center
      • Department of Surgery
      Durham, North Carolina, United States
  • 2011–2012
    • Montefiore Medical Center
      • The Children's Hospital at Montefiore
      New York City, New York, United States
    • NCI-Frederick
      Maryland, United States
  • 2008–2012
    • University of New South Wales
      • Children’s Cancer Institute of Australia
      Kensington, New South Wales, Australia
    • National Botanical Research Institute - India
      Lakhnau, Uttar Pradesh, India
    • National Cancer Institute (USA)
      • Cancer Therapy Evaluation Program
      Maryland, United States
    • The Children’s Hospital at Montefiore (CHAM)
      New York City, New York, United States
  • 2003–2012
    • Royal Botanic Gardens, Kew
      • Jodrell Laboratory
      TW9, England, United Kingdom
  • 1989–2012
    • King's College London
      • Department of Pharmacy
      Londinium, England, United Kingdom
  • 2009–2011
    • University of Lisbon
      • Faculty of Pharmacy
      Lisboa, Lisbon, Portugal
  • 2008–2011
    • Nemours
      Jacksonville, Florida, United States
    • Hospital of the University of Pennsylvania
      Philadelphia, Pennsylvania, United States
  • 2007–2011
    • ICL
      Londinium, England, United Kingdom
    • The Kings College
      Eidson Road, Texas, United States
  • 2008–2010
    • Kwame Nkrumah University Of Science and Technology
      • Faculty of Pharmacy and Pharmaceutical Sciences
      Kumasi, Ashanti Region, Ghana
  • 2004–2010
    • Università della Calabria
      • Department of Pharmacy, Health and Nutritional Sciences
      Rende, Calabria, Italy
    • University of Mysore
      Mahisūr, Karnātaka, India
    • Chinese Academy of Medical Sciences
      Peping, Beijing, China
    • Chulalongkorn University
      • Faculty of Pharmaceutical Sciences
      Bangkok, Bangkok, Thailand
  • 1992–2010
    • St. Jude Children's Research Hospital
      • • Department of Pharmaceutical Sciences
      • • Department of Biostatistics
      Memphis, Tennessee, United States
  • 2007–2008
    • Jadavpur University
      • Department of Pharmaceutical Technology
      Calcutta, Bengal, India
  • 2005–2008
    • Aga Khan University Hospital, Karachi
      • Department of Medicine
      Kurrachee, Sindh, Pakistan
    • Western Illinois University
      • Chemistry
      Macomb, IL, United States
    • Bristol-Myers Squibb
      • Clinical Discovery
      New York City, NY, United States
  • 2003–2005
    • University of Maryland, Baltimore
      • Greenebaum Cancer Center
      Baltimore, Maryland, United States
  • 1991–2004
    • King College
      Franklin, Tennessee, United States
  • 2002
    • University of London
      • The School of Pharmacy
      London, ENG, United Kingdom
  • 1997–2000
    • University of Tennessee
      Knoxville, Tennessee, United States
  • 1993
    • University of Nigeria
      Nsukka, Enugu State, Nigeria