Elizabeth R. Sharlow
- BA, Pennsylvania State University, University Park, PA
- PhD, Pennsylvania State University, University Park, PA
- Associate Professor, Pharmacology
Exploiting chemical biology approaches to understand signaling pathways that are critical for parasite, neuronal and tumor cell viability
The identification and validation of molecular targets are critical for discovering the intracellular signaling mechanisms that control cell and organism viability. These molecular targets form the foundation for the generation of new pharmacological agents.
My main research focus is on neglected diseases. In general, genome sequencing studies have greatly accelerated and supported small molecule, target-based approaches, although they have not provided significant insights into the molecular targets vital to parasitic growth, survival, invasion and life-cycle. Thus, to complement these genome sequencing efforts, I am using integrated high throughput screening methodologies with targeted and diversity-based compound libraries to identify novel and specific small molecule inhibitors of proteins and pathways that are critical to intraparasitic signaling.
Additional research efforts target the identification and development of specific and potent small molecule inhibitors for Protein kinase D (PKD), Polo-like Kinase 1 (PLK1) and Polo-kinase 2 (PLK2). Each of these proteins play critical roles in the signaling pathways of neuronal and tumor cell viability; however, functional studies have been hindered by the lack of specific, potent inhibitory compounds.
- Axelrod M, Gordon V, Mendez R, Leimgruber S, Conaway M, Sharlow E, Jameson M, Gioeli D, Weber M. p70S6 kinase is a critical node that integrates HER-family and PI3 kinase signaling networks. Cellular signalling. 2014. PMID: 24662264 | PMCID: PMC4091927
- Axelrod M, Mendez R, Khalil A, Leimgruber S, Sharlow E, Capaldo B, Conaway M, Gioeli D, Weber M, Jameson M. Synergistic apoptosis in head and neck squamous cell carcinoma cells by co-inhibition of insulin-like growth factor-1 receptor signaling and compensatory signaling pathways. Head & neck. 2014. PMID: 24986420
- Sharlow E, Wipf P, McQueeney K, Bakan A, Lazo J. Investigational inhibitors of PTP4A3 phosphatase as antineoplastic agents. Expert opinion on investigational drugs. 2014;23(5): 661-73. PMID: 24625356
- Lazo J, Sharlow E, Epperly M, Lira A, Leimgruber S, Skoda E, Wipf P, Greenberger J. Pharmacologic profiling of phosphoinositide 3-kinase inhibitors as mitigators of ionizing radiation-induced cell death. The Journal of pharmacology and experimental therapeutics. 2013;347(3): 669-80. PMID: 24068833 | PMCID: PMC3836314
- Sharlow E, Leimgruber S, Murray S, Lira A, Sciotti R, Hickman M, Hudson T, Leed S, Caridha D, Barrios A, Close D, Grögl M, Lazo J. Auranofin is an apoptosis-simulating agent with in vitro and in vivo anti-leishmanial activity. ACS chemical biology. 2013;9(3): 663-72. PMID: 24328400
- George K, Frantz M, Bravo-Altamirano K, Lavalle C, Tandon M, Leimgruber S, Sharlow E, Lazo J, Wang Q, Wipf P. Design, Synthesis, and Biological Evaluation of PKD Inhibitors. Pharmaceutics. 2012;3(2): 186-228. PMID: 22267986 | PMCID: PMC3261798
- Bravo-Altamirano K, George K, Frantz M, Lavalle C, Tandon M, Leimgruber S, Sharlow E, Lazo J, Wang Q, Wipf P. Synthesis and Structure-Activity Relationships of Benzothienothiazepinone Inhibitors of Protein Kinase D. ACS medicinal chemistry letters. 2011;2(2): 154-159. PMID: 21617763 | PMCID: PMC3100199
- Sharlow E, Mustata Wilson G, Close D, Leimgruber S, Tandon M, Reed R, Shun T, Wang Q, Wipf P, Lazo J. Discovery of diverse small molecule chemotypes with cell-based PKD1 inhibitory activity. PloS one. 2011;6(10): e25134. PMID: 21998636 | PMCID: PMC3187749
- LaValle C, George K, Sharlow E, Lazo J, Wipf P, Wang Q. Protein kinase D as a potential new target for cancer therapy. Biochimica et biophysica acta. 2010;1806(2): 183-92. PMID: 20580776 | PMCID: PMC2947595
- Lavalle C, Bravo-Altamirano K, Giridhar K, Chen J, Sharlow E, Lazo J, Wipf P, Wang Q. Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility. BMC chemical biology. 2010;10 5. PMID: 20444281 | PMCID: PMC2873968
- Sharlow E, Lyda T, Dodson H, Mustata G, Morris M, Leimgruber S, Lee K, Kashiwada Y, Close D, Lazo J, Morris J. A target-based high throughput screen yields Trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity. PLoS neglected tropical diseases. 2010;4(4): e659. PMID: 20405000 | PMCID: PMC2854128
- Shah P, Myers M, Beavers M, Purvis J, Jing H, Grieser H, Sharlow E, Napper A, Huryn D, Cooperman B, Smith A, Diamond S. Kinetic characterization and molecular docking of a novel, potent, and selective slow-binding inhibitor of human cathepsin L. Molecular pharmacology. 2008;74(1): 34-41. PMID: 18403718 | PMCID: PMC2575030
- Sharlow E, Giridhar K, LaValle C, Chen J, Leimgruber S, Barrett R, Bravo-Altamirano K, Wipf P, Lazo J, Wang Q. Potent and selective disruption of protein kinase D functionality by a benzoxoloazepinolone. The Journal of biological chemistry. 2008;283(48): 33516-26. PMID: 18829454 | PMCID: PMC2586241