Shane Foister Assistant Professor Organic Chemistry Bio-organic Chemistry; chemical biology; medicinal chemistry. B.S., University of Kentucky (1998) Ph.D., California Institute of Technology (2003) NSF Graduate Fellow
E-mail: foister@ion.chem.utk.edu Buehler Hall   ·   Telephone: 865-974-3419 Representative publications   ·   Biographical sketch

Research

My group's research interests reside at the interface between chemistry and biology where the vast arsenal of synthetic organic chemistry can be directed by biophysical insights taken from "Nature's notebook." Our primary goal is the development of therapeutic agents relevant to the prevention, detection, or treatment of cancer, neurodegenerative diseases, and environmental pathogens. In this regard, we apply traditional synthetic chemistry to the synthesis of natural products and analogs designed with the aid of molecular modeling. Solid phase synthetic techniques are also employed in the construction of small molecule and peptidomimetic libraries which allow the biochemistry of disease pathologies to be examined with molecular detail in high throughput formats. An additional area of focus is the development of prodrug and targeting agents which can be used to improve the efficacy and reduce the toxicity of potential drugs.

The aberrant regulation of natural processes, including programmed cell death, is a hallmark of several human diseases including cancer and neurological disorders. In cancer, tumors acquire malignant phenotypes that allow them to evade cell death by ignoring or repressing pro-apoptotic signals, resulting in uncontrolled growth, drug resistance, and even metastasis. Our approach to chemotherapeutic development targets multiple pathways in the progression of cancer, including inhibition of oncogenic transcription factors responsible for drug resistance, activation of apoptosis by inhibition of histone deacetylases, as well as blockade of the metastatic cascade. Distinct warheads aimed at the above processes will be combined via cancer-targeted prodrug moieties.

In contrast to cancer, neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by unscheduled apoptosis leading to the loss of specific populations of neurons. Thus, our approach to the development of AD or PD therapeutics focuses on finding small molecules or combinations thereof able to halt premature cell death. Research in this area examines the role played by misfolded oligomeric proteins in generating mitochondrial and endoplasmic reticulum stress. The ability of these soluble oligomers to interact with intracellular proteins and initiate stress and ultimately apoptosis will be explored with the aim of developing peptidomimetic ligands capable of disrupting pathogenic protein-protein interactions.

Representative publications

Warren, C. L.; Kratochvil, N. C.; Hauschild, K. E.; Foister, S.; Brezinski, M. L.; Dervan, P. B.; Phillips, G. N.; Ansari, A. Z. "Defining the sequence-recognition profile of DNA-binding molecules." Proc. Natl. Acad. Sci. USA 2006, 103, 867-72.

Marques, M. A.; Doss, R. M.; Foister, S. ; Dervan, P. B. "Expanding the Repertoire of Heterocycle Ring Pairs for Programmable Minor Groove DNA Recognition." J. Am. Chem. Soc. 2004, 126, 10339.

Doss, R. M.; Marques, M. A.; Foister, S. ; Dervan, P. B. "Analysis of DNA Minor Groove Recognition by the 3-Methylthiophene/Pyrrole Pair." Chemistry and Biodiversity, 2004, 1, (6) 886-899.

Edelson, B. S.; Best, T. P.; Olenyuk, B.; Nickols, N. G.; Doss, R. M.; Foister, S.; Heckel, A.; Dervan, P. B. "Influence of structural variation on nuclear localization of DNA-binding polyamide-fluorophore conjugates." Nuc. Acids Res. 2004, 32, 2802.

Foister, S.; Marques, M. A.; Doss, R. D.; Dervan, P. B. "Shape Selective Recognition of T·A Base Pairs by Hairpin Polyamides Containing N-Terminal 3-Methoxy (and 3-Chloro) Thiophene Residues," Bioorg. Med. Chem. 2003, 11, 4333.

Rucker, V. C.; Foister, S.; Melander, C.; Dervan, P. B. "Sequence Specific Fluorescent Detection of Double Strand DNA," J. Am. Chem. Soc. 2003, 125, 1195.

Biographical sketch

Dr. Foister received his B.S. in Chemistry from the University of Kentucky in 1998, working in the laboratories of Professor Arthur Cammers on predictive aspects of peptide secondary structure. He completed his Ph.D. at the California Institute of Technology in 2003, under the supervision of Professor Peter Dervan, in the field of nucleic acid recognition. Dr. Foister then pursued postdoctoral studies at the University of Pennsylvania with the guidance of Professors Ralph Hirschmann and Amos B. Smith III. Dr. Foister joined the faculty at the University of Tennessee in 2006.