Experts and Doctors on sirolimus in Memphis, Tennessee, United States


Locale: Memphis, Tennessee, United States
Topic: sirolimus

Top Publications

  1. Keating R, Hertz T, Wehenkel M, Harris T, Edwards B, McClaren J, et al. The kinase mTOR modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus. Nat Immunol. 2013;14:1266-76 pubmed publisher
    ..Our findings have implications for the design of a vaccine against influenza virus. ..
  2. Tate J, Rai R, Cooper T. Methionine sulfoximine treatment and carbon starvation elicit Snf1-independent phosphorylation of the transcription activator Gln3 in Saccharomyces cerevisiae. J Biol Chem. 2005;280:27195-204 pubmed
  3. Thimmaiah K, Easton J, Houghton P. Protection from rapamycin-induced apoptosis by insulin-like growth factor-I is partially dependent on protein kinase C signaling. Cancer Res. 2010;70:2000-9 pubmed publisher
    ..Collectively, these data suggest that IGF-I-induced phosphorylation of Bad at multiple sites via a pathway involving PI3K and PKCs is important for protecting sarcoma cells from rapamycin-induced apoptosis. ..
  4. Dilling M, Germain G, Dudkin L, Jayaraman A, Zhang X, Harwood F, et al. 4E-binding proteins, the suppressors of eukaryotic initiation factor 4E, are down-regulated in cells with acquired or intrinsic resistance to rapamycin. J Biol Chem. 2002;277:13907-17 pubmed
    ..These results suggest that the 4E-BP:eIF4E ratio is an important determinant of rapamycin resistance and controls certain aspects of the malignant phenotype. ..
  5. Huang S, Houghton P. Mechanisms of resistance to rapamycins. Drug Resist Updat. 2001;4:378-91 pubmed
    ..To better explore the role of rapamycins against tumors, this review will summarize the current knowledge of the mechanism of action of rapamycins, and progress in understanding mechanisms of acquired or intrinsic resistance. ..
  6. Rai R, Tate J, Nelson D, Cooper T. gln3 mutations dissociate responses to nitrogen limitation (nitrogen catabolite repression) and rapamycin inhibition of TorC1. J Biol Chem. 2013;288:2789-804 pubmed publisher
    ..We also found that Gln3 possesses at least one Tor1-interacting site in addition to the one previously reported...
  7. Huang S, Shu L, Easton J, Harwood F, Germain G, Ichijo H, et al. Inhibition of mammalian target of rapamycin activates apoptosis signal-regulating kinase 1 signaling by suppressing protein phosphatase 5 activity. J Biol Chem. 2004;279:36490-6 pubmed
    ..The findings suggest that in the absence of serum factors, mTOR signaling suppresses apoptosis through positive regulation of PP5 activity and suppression of cellular stress. ..
  8. Easton J, Houghton P. Therapeutic potential of target of rapamycin inhibitors. Expert Opin Ther Targets. 2004;8:551-64 pubmed
  9. Tate J, Georis I, Feller A, Dubois E, Cooper T. Rapamycin-induced Gln3 dephosphorylation is insufficient for nuclear localization: Sit4 and PP2A phosphatases are regulated and function differently. J Biol Chem. 2009;284:2522-34 pubmed publisher

More Information


  1. Shen C, Lancaster C, Shi B, Guo H, Thimmaiah P, Bjornsti M. TOR signaling is a determinant of cell survival in response to DNA damage. Mol Cell Biol. 2007;27:7007-17 pubmed
    ..Thus, TOR-dependent cell survival in response to DNA-damaging agents coincides with increased mutation rates, which may contribute to the acquisition of chemotherapeutic drug resistance. ..
  2. Shu L, Zhang X, Houghton P. Myogenic differentiation is dependent on both the kinase function and the N-terminal sequence of mammalian target of rapamycin. J Biol Chem. 2002;277:16726-32 pubmed
    ..In contrast, constitutive activation of S6K1 does not abrogate rapamycin inhibition of either proliferation or myogenic differentiation. ..
  3. Shu L, Houghton P. The mTORC2 complex regulates terminal differentiation of C2C12 myoblasts. Mol Cell Biol. 2009;29:4691-700 pubmed publisher
    ..Further, the ROCK inhibitor Y-27632 restored terminal differentiation in rapamycin-treated myoblasts. These results provide the first evidence of a specific role for mTORC2 signaling in terminal myogenic differentiation. ..
  4. Tate J, Cooper T. Stress-responsive Gln3 localization in Saccharomyces cerevisiae is separable from and can overwhelm nitrogen source regulation. J Biol Chem. 2007;282:18467-80 pubmed
    ..Together these data identify a major new level of regulation to which Gln3 responds, and adds a new dimension to mechanistic studies of the regulation of this transcription factor. ..
  5. Zhan J, Easton J, Huang S, Mishra A, Xiao L, Lacy E, et al. Negative regulation of ASK1 by p21Cip1 involves a small domain that includes Serine 98 that is phosphorylated by ASK1 in vivo. Mol Cell Biol. 2007;27:3530-41 pubmed
    ..Binding of p21(Cip1) to ASK1 requires ASK1 kinase function and may involve phosphorylation of S98. ..
  6. Tate J, Feller A, Dubois E, Cooper T. Saccharomyces cerevisiae Sit4 phosphatase is active irrespective of the nitrogen source provided, and Gln3 phosphorylation levels become nitrogen source-responsive in a sit4-deleted strain. J Biol Chem. 2006;281:37980-92 pubmed
    ..In some strains, Sit4 was not even required for Gln3 nuclear localization in untreated or rapamycin-treated, proline-grown cells or Msx-treated, ammonia-grown cells. ..
  7. Houghton P, Huang S. mTOR as a target for cancer therapy. Curr Top Microbiol Immunol. 2004;279:339-59 pubmed
    ..Further, a rationale for anticipating tumor-selective activity based on transforming events frequently identified in malignant disease is becoming established. ..
  8. Huang S, Shu L, Dilling M, Easton J, Harwood F, Ichijo H, et al. Sustained activation of the JNK cascade and rapamycin-induced apoptosis are suppressed by p53/p21(Cip1). Mol Cell. 2003;11:1491-501 pubmed
    ..These results suggest that inhibition of mTOR triggers a potentially lethal response that is prevented only in cells expressing p21(Cip1). ..
  9. Kurmasheva R, Dudkin L, Billups C, Debelenko L, Morton C, Houghton P. The insulin-like growth factor-1 receptor-targeting antibody, CP-751,871, suppresses tumor-derived VEGF and synergizes with rapamycin in models of childhood sarcoma. Cancer Res. 2009;69:7662-71 pubmed publisher
    ..These data suggest a model in which blockade of IGF-1R suppresses tumor-derived VEGF to a level where rapamycin can effectively suppress the response in vascular endothelial cells. ..
  10. Tate J, Georis I, Dubois E, Cooper T. Distinct phosphatase requirements and GATA factor responses to nitrogen catabolite repression and rapamycin treatment in Saccharomyces cerevisiae. J Biol Chem. 2010;285:17880-95 pubmed publisher
  11. Morton C, Maris J, Keir S, Gorlick R, Kolb E, Billups C, et al. Combination testing of cediranib (AZD2171) against childhood cancer models by the pediatric preclinical testing program. Pediatr Blood Cancer. 2012;58:566-71 pubmed publisher
    ..By contrast, the combination of cediranib with rapamycin was additive or supra-additive in four of the six models in terms of prolongation of time to event, though tumor regressions were not observed for this combination. ..
  12. Mody R, Naranjo A, Van Ryn C, Yu A, London W, Shulkin B, et al. Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial. Lancet Oncol. 2017;18:946-957 pubmed publisher
    ..Further evaluation of biomarkers in a larger cohort of patients might identify those most likely to respond to this chemoimmunotherapeutic regimen. National Cancer Institute. ..