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Hire Dr. Keith L.

United States

USD 70 /hr

Experienced investigator of the responses of mammalian cells to diverse stresses including cytotoxic/cytostatic agents

Profile Summary

Conducted research projects involving small-molecule drug discovery, particularly in response to stress conditions commonly found in solid tumor microenvironments. Assisted as a biologist in the development of computational tools to represent and analyze large biochemical networks such as mammalian signaling systems involved in proliferation, survival, and metabolism. Maintained substantial grant-supported research funding (primarily NIH/NCI projects) in a private research organization setting. Respected and adaptable team player/leader, committed to advancing biomedical research and promoting related technology development.

Subject Matter Expertise

• ★ Molecular Biology
• ★ Cancer Research
• ☆ Biotechnology & Bioengineering
• ☆ Pharmaceutical Sciences
• ☆ Oncology

Services

• Writing
• Research

Writing Technical Writing

Research Fact Checking, Gray Literature Search, Systematic Literature Review, Secondary Data Collection

Work Experience

Senior Research Scientist

SRI International

2008 - 2020

Director, Cancer Biology Program

SRI International

1994 - 2008

Cancer Biologist

SRI International

1989 - 1994

Research Associate

National Research Council Canada

1987 - 1989

Education

Postdoctoral Fellow (Physics Division)

Ontario Cancer Institute

1984 - 1987

PhD (Organic Chemistry)

University of Toronto

- 1985

Certifications

• Certification details not provided.

Publications

CONFERENCE ABSTRACT

(2016). Abstract B36: Developing circRNA signatures as a biomarker for the early diagnosis of pancreatic carcinoma. AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines.

JOURNAL ARTICLE

(2014). 5'-AMP-activated protein kinase (AMPK) supports the growth of aggressive experimental human breast cancer tumors . The Journal of biological chemistry.

(2012). Transcriptional regulation of gene expression during osmotic stress responses by the mammalian target of rapamycin . Nucleic acids research.

(2012). Ionizing radiation regulates the expression of AMP-activated protein kinase (AMPK) in epithelial cancer cells: modulation of cellular signals regulating cell cycle and survival . Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

(2011). The AMPK stress response pathway mediates anoikis resistance through inhibition of mTOR and suppression of protein synthesis . Cell death and differentiation.

(2011). 5'-AMP-activated protein kinase activity is elevated early during primary brain tumor development in the rat . International journal of cancer.

(2010). SR16388: a steroidal antiangiogenic agent with potent inhibitory effect on tumor growth in vivo . Angiogenesis.

(2010). The rational design of a novel potent analogue of the 5'-AMP-activated protein kinase inhibitor compound C with improved selectivity and cellular activity . Bioorganic & medicinal chemistry letters.

(2010). SU11248 (sunitinib) directly inhibits the activity of mammalian 5'-AMP-activated protein kinase (AMPK) . Cancer biology & therapy.

(2010). A novel steroidal inhibitor of estrogen-related receptor alpha (ERR alpha) . Biochemical pharmacology.

(2010). The metal-responsive transcription factor-1 protein is elevated in human tumors . Cancer biology & therapy.

(2009). Selective deficiency of HIF-1alpha in myeloid cells influences secondary intention wound healing in mouse skin. In vivo (Athens, Greece).

(2009). A novel peroxisome proliferator-activated receptor delta antagonist, SR13904, has anti-proliferative activity in human cancer cells . Cancer biology & therapy.

(2009). Integrated analysis of breast cancer cell lines reveals unique signaling pathways . Genome biology.

(2008). Changes to NIH grant system may backfire . Science (New York, N.Y.).

(2008). Hypoxia signals autophagy in tumor cells via AMPK activity, independent of HIF-1, BNIP3, and BNIP3L . Cell death and differentiation.

(2008). AMP-activated protein kinase inhibits transforming growth factor-beta-induced Smad3-dependent transcription and myofibroblast transdifferentiation . The Journal of biological chemistry.

(2006). 5'-AMP-activated protein kinase (AMPK) is induced by low-oxygen and glucose deprivation conditions found in solid-tumor microenvironments . Molecular and cellular biology.

(2005). The metal-responsive transcription factor-1 contributes to HIF-1 activation during hypoxic stress . Biochemical and biophysical research communications.

(2005). The interaction between HIF-1 and AP-1 transcription factors in response to low oxygen . Seminars in cell & developmental biology.

(2004). Glucose utilization is essential for hypoxia-inducible factor 1 alpha-dependent phosphorylation of c-Jun . Molecular and cellular biology.

(2004). Pathway logic modeling of protein functional domains in signal transduction. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing.

(2002). The response of c-jun/AP-1 to chronic hypoxia is hypoxia-inducible factor 1 alpha dependent . Molecular and cellular biology.

(2002). Pathway logic: symbolic analysis of biological signaling. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing.

(2001). The novel tubulin-binding drug BTO-956 inhibits R3230AC mammary carcinoma growth and angiogenesis in Fischer 344 rats. Clinical cancer research : an official journal of the American Association for Cancer Research.

(2001). c-jun cooperates with SV40 T-antigen to sustain MMP-2 expression in immortalized cells . Biochemical and biophysical research communications.

(2001). Transcription factor HIF-1 is a necessary mediator of the pasteur effect in mammalian cells . Molecular and cellular biology.

(2001). Placenta growth factor gene expression is induced by hypoxia in fibroblasts: a central role for metal transcription factor-1. Cancer research.

(2000). Opposing effects of hypoxia on expression of the angiogenic inhibitor thrombospondin 1 and the angiogenic inducer vascular endothelial growth factor. Clinical cancer research : an official journal of the American Association for Cancer Research.

(2000). Altered splicing of the ATDC message in ataxia telangiectasia group D cells results in the absence of a functional protein . Mutagenesis.

(2000). Epigenetic regulation of gene expression in cervical cancer cells by the tumor microenvironment. Clinical cancer research : an official journal of the American Association for Cancer Research.

(1999). Mitogen-activated protein kinase phosphatase-1 (MKP-1) expression is induced by low oxygen conditions found in solid tumor microenvironments. A candidate MKP for the inactivation of hypoxia-inducible stress-activated protein kinase/c-Jun N-terminal protein kinase activity . The Journal of biological chemistry.

(1999). Activation of metallothionein gene expression by hypoxia involves metal response elements and metal transcription factor-1. Cancer research.

(1998). Inhibition of human bladder cancer cell motility by genistein is dependent on epidermal growth factor receptor but not p21ras gene expression. International journal of cancer.

(1998). Epidermal growth factor receptor-regulated human bladder cancer motility is in part a phosphatidylinositol 3-kinase-mediated process. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

(1998). Oncocidin A1: a novel tubulin-binding drug with antitumor activity against human breast and ovarian carcinoma xenografts in nude mice . Biochemical pharmacology.

(1998). The redox-sensitive human antioxidant responsive element induces gene expression under low oxygen conditions . Carcinogenesis.

(1997). Induction of vascular endothelial growth factor by hypoxia is modulated by a phosphatidylinositol 3-kinase/Akt signaling pathway in Ha-ras-transformed cells through a hypoxia inducible factor-1 transcriptional element. Blood.

(1997). Protease inhibitor TPCK represses Ha-ras (Val12) transformation and nuclear factor-kappa B activation. International journal of oncology.

(1997). Hypoxia/reoxygenation stimulates Jun kinase activity through redox signaling in cardiac myocytes . Circulation research.

(1996). Oncogenic transformation and hypoxia synergistically act to modulate vascular endothelial growth factor expression. Cancer research.

(1996). Expression of the ATDC (ataxia telangiectasia group D-complementing) gene in A431 human squamous carcinoma cells. International journal of cancer.

(1996). Early responses of SiHa human squamous carcinoma cells to hypoxic signals. International Journal of Oncology.

(1996). Tumor Hypoxia and Heterogeneity: Challenges and Opportunities for the Future . Seminars in radiation oncology.

(1996). Fused pyrazine mono-n-oxides as bioreductive drugs. II Cytotoxicity in human cells and oncogenicity in a rodent transformation assay . International journal of radiation oncology, biology, physics.

(1995). Mapping of the vascular endothelial growth factor-producing hypoxic cells in multicellular tumor spheroids using a hypoxia-specific marker. Cancer research.

(1994). Metallothionein IIA is up-regulated by hypoxia in human A431 squamous carcinoma cells. Cancer research.

(1994). Regulation of c-jun expression during hypoxic and low-glucose stress . Molecular and cellular biology.

(1994). Synergistic interaction between tirapazamine and cyclophosphamide in human breast cancer xenografts. Cancer research.

(1994). Epidermal growth factor modifies cell cycle control in A431 human squamous carcinoma cells damaged by ionizing radiation. Cancer research.

(1993). Enhancement of heme oxygenase expression and activity in A431 squamous carcinoma multicellular tumor spheroids. Cancer research.

(1992). Enhanced epidermal growth factor receptor synthesis in human squamous carcinoma cells exposed to low levels of oxygen . International journal of cancer.

(1992). Bipartite organization of the Bacillus subtilis endo-beta-1,4-glucanase revealed by C-terminal mutations . Protein engineering.

(1992). Enhancement of transforming growth factor-alpha synthesis in multicellular tumour spheroids of A431 squamous carcinoma cells . British journal of cancer.

(1991). Hypoxia-induced drug resistance: comparison to P-glycoprotein-associated drug resistance . British journal of cancer.

(1991). The identification of heme oxygenase as a major hypoxic stress protein in Chinese hamster ovary cells . British journal of cancer.

(1991). Oxygen regulated 80 kDa protein and glucose regulated 78kDa protein are identical . Molecular and cellular biochemistry.

(1989). NLP-1: a DNA intercalating hypoxic cell radiosensitizer and cytotoxin . International journal of radiation oncology, biology, physics.

(1988). Molecular mechanisms for the hypoxia-dependent activation of 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) . Biochemical pharmacology.

(1986). The production of strand breaks in DNA in the presence of the hydroxylamine of SR-2508 (1-[N-(2-hydroxyethyl)acetamido]-2-nitroimidazole) at neutral pH . International journal of radiation oncology, biology, physics.

(1986). The production of strand breaks in DNA in the presence of the hydroxylamine of SR-2508 (1-[N-(2-hydroxyethyl)acetamido]-2-nitroimidazole) at neutral pH . International journal of radiation oncology, biology, physics.

(1985). K. R. Laderoute and A. G. Harrison. Concerning the equilibration of oxygen atoms in the molecular ions of methyl esters. Org. Mass Spectrom. 20, 374-376, 1985.

(1985). K. R. Laderoute and A. G. Harrison. Cyclopropane intermediates in the rearrangement and fragmentation of olefinic molecular ions. Org. Mass Spectrom. 20, 624-630, 1985.

(1985). K. R. Laderoute, J. J. Zwinselman, and A. G. Harrison. Characterization of five [C4H7O]+ Ion Structures. Fragmentation of the 2-pentanone molecular ion. Org. Mass Spectrom. 20, 25-33, 1985.

(1980). J. W. Bunting, K. R. Laderoute, and D. J. Norris. The pH dependence of xanthine oxidase catalysis in basic solution. Can. J. Biochem. 58, 394-398, 1980.

(1980). J. W. Bunting, K. R. Laderoute, and D. J. Norris. Specificity of xanthine oxidase for nitrogen heteroaromatic cation substrates. Can. J. Biochem. 58, 49-57, 1980.

CONFERENCE PAPER

(2007). A. Tiwari, C. Talcott, M. Knapp, P. Lincoln, and K. Laderoute. Analyzing biological pathways using SAT-based approaches.

(2007). B. Parvin, N. Ghosh, L. Heiser, M. Knapp, C. Talcott, K. Laderoute, J. Gray, and P. Spellman. Spectral decomposition of signaling networks. Proceedings of the IEEE Symposium on Computational Intelligence in Bioinformatics and Computational Biology, April 1-5, 2007, Honolulu, HI.

(2003). S. Eker, K. Laderoute, P. Lincoln, M. G. Sriram, C. Talcott. Representing and simulating protein functional domains in signal transduction using MAUDE. International Workshop on Computational Methods in Systems Biology. February 24-26, 2003, Roverto Italy. Springer-Verlag.

(2002). Steven Eker, Merrill Knapp, Patrick Lincoln, Keith Laderoute, Carolyn Talcott. Pathway Logic: Executable models of biological networks. 4th International Workshop on Rewriting Logic and its Applications (WRLA’2002). September 19-21, 2002, Pisa, Italy. Springer-Verlag.

(1991). R. M. Sutherland, W. A. Ausserer, T. D. Grant, A. M. Knapp, T. T. Kwok, K. R. Laderoute, S. C. Miller, and J. N. Mansbridge. Regulatory polypeptide growth factors, signal transduction, and radiation response. Ninth International Conference on Radiation Research, 1991, Toronto, Ontario: Academic Press.

PATENT

(2002). D. Tuse', C. Hiebert, K. R. Laderoute, and N. Waleh. Method for inhibiting inflammatory disease.

(2001). K. A. Webster, N. H. Bishopric, B. Murphy, K. R. Laderoute, and C. J. Green. Tissue specific hypoxia regulated constructs.

(2001). D. Tuse', X. Chen, C. K. Hiebert, C. M. Olsen, K. Laderoute, N. Waleh, and A. M. Knapp. Di-aryl ethers and their derivatives as anti-cancer agents.

(2000). D. Tuse', C. Hiebert, K. R. Laderoute, and N. Waleh. Methods for inhibiting angiogenesis.