Program Alumni

2005-2007 Trainees	Home Department	CBI Mentor
Lisa Cooper, Ph.D., 2009 Research Description: Lantibiotics are a class of peptide-derived antimicrobial agents. They are ribosomally synthesized as inactive precursor peptides that subsequently undergo post-translational modification by a multienzyme complex to their mature, biologically active forms. All lantibiotics contain lanthionine and/or methyllanthionine residues and also typically the unsaturated amino acids dehydroalanine and dehydrobutyrine. These structural motifs are the bases for their function. My research has spanned three different class II lantibiotics: lacticin 481, haloduracin, and cinnamycin. For lacticin 481, I completed my initial projects 1) exploring the role of the "double glycine" motif in the leader sequence, and 2) examining the consequences of changing the residues that flank the hydroxy amino acids in the structural region. After successfully engineering an in vitro haloduracin production system, I studied the structural features essential for this antibiotic's activity. Towards the end of my stay at Illinois, I worked towards the in vitro reconstitution of cinnamycin biosynthesis.	Biochemistry	Wilfred van der Donk
Jill Gunther, Ph.D., 2009 Research Description: Carbonic Anhydrase 12 is a membrane-associated enzyme that regulates cellular pH and is present in both breast and prostate tumors. Because CA12 is a primary response gene under regulation by estrogen, it should act as a reliable monitor of estrogen receptor function within these tumors. I refined an assay to test the binding affinities of fluorine-substituted CA12 inhibitors and worked to express and purify this protein. In vivo imaging of these tumors by positron-emission tomography (PET) using these inhibitors in fluorine-18 labeled form, before and after a hormone challenge, should report on the functionality of estrogen receptor action and, therefore, be predictive of effectiveness of hormone therapy in the treatment of these cancers. I also examined classes of ER subtype-selective ligands that show much higher selectivity in terms of transcriptional potency (EC₅₀ values) than in terms of binding affinities (K_i values). I used coactivator-interaction assays to investigate whether these difference reflect error in assay or significant subtype discrimination at the level of the interaction of the ER-ligand complex with coactivators.	Chemistry (Chemical Biology) Medical Scholars Program	John Katzenellebogen
John Rakus, Ph.D., 2009 Research Description: Uncovering functional diversity within the enolase superfamily and identifying substrate diversity within individual members of the superfamily can give us clues as to how enzymes with nearly universally conserved active site architecture can evolve many disparate functions. To that end my research was somewhat two-pronged. I characterized several enolase superfamily members from the soil bacterium Polaromonas sp JS666 which currently have unknown function and unclear genomic context. The GI numbers for these proteins are 67847749, 67910434 and 67928240. Additionally,I took a member of known function, rhamnonate dehydratase from Escherichia coli and characterized the chemical basis for its mechanism as well as specific interactions involved in this protein's substrate specificity.	Biochemistry	John Gerlt
Paul Thomas, Ph.D. 2008 Research Description: The coactivator p300 and the estrogen receptor are two of the many regulators of RNA polymerase II mediated transcription through direct and indirect histone modifications. While p300 is known for its chromatin remodeling activity, it is also part of a signal cascade and is known to be post-translationally methylated and phosphorylated. The estrogen receptor is known to be multiply phosphorylated and acetylated. It is believed that these modifications play a role in the transcriptional activation and silencing. My research focused on the direct analysis of these transcription factors in vivo to determine their modification states and patterns using multidimensional liquid chromatography coupled to mass spectrometry. This allows determination of the modification states and patterns of these proteins throughout the cell cycle and helps to ascertain any changes that may occur upon treatment with DNA binding drugs such as cisplatin.	Chemistry (Analytical)	Neil Kelleher