Spring 2013 Courses

Experimental Chemistry III

Experimental Biochemistry

Chemistry Capstone

Bio

I began studying chemistry at Temple University and had my first research experience in the lab of Grant Krow.  There, I worked on a hetero-Diels Alder reaction and regioselective alkene functionalization towards the synthesis of homo-epibatidine.  After Temple, I began graduate work at Princeton in the lab of Kevan Shokat.  There I did work on protein engineering to alter the nucleotide substrate preference of protein tyrosine kinases to identify their downstream signaling partners as well as design and synthesis of histone deacetylase inhibitors. 

Research in Biological Chemistry

There are several projects ongoing in the lab, all of which involve using chemistry to elucidate or control biological systems. 

We are currently developing inhibitors of a bacterial communication system called "quorum sensing". Quorum sensing involves the synthesis, secretion and detection of low molecular weight compounds called autoinducers.  Autoinducer signaling controls bacterial gene expression and behavior.  Some bacterial behaviors regulated by quorum sensing have to do with pathogenesis, so blocking quorum sensing is of interest to produce new types of antibacterial compounds.  Importantly, such antibiotics will not be lethal to the bacteria and will not exert the severe selective pressure to drive antibiotic resistance. Our group has projects to synthesize inhibitors of autoinducer synthase enzymes and antagonists of autoinducer receptors.  We are also interested in reprogramming autoinducer receptors to recognize synthetic, unnatural autoinducers to gain control over their signaling.

We also work on the terpene cyclase enzyme superfamily.  Terpenes are natural products used as medicines (taxol, artemesinin), fragrances and flavorants (limonene, citronellal).  Terpene cyclases are enzymes that ionize polyalkene precursors and promote specific rearrangements of the resulting carbocation to generate the staggering diversity of terpene scaffolds.  We are interested in synthesizing stable analogs of the carbocationic intermediates to help understand how the cyclases manage the carbocation chemistry.

Our research has been supported by the American Chemical Society and the Research Corporation.

Research Group Alumni

Undergraduate students in my lab often learn various techniques such as organic synthesis, basic molecular biology, protein expression/purification, enzymology, and microbiology.  Alumni have often gone on to graduate and medical schools. Below is a list of some of my former students and where they went after IC:

• Nate Heldt, MD/PhD aspirant.
• Leah Graham, PhD student at Tufts University
• Cornell Conca- Medical School at New York Medical College
• Alyson Waring- Vet School
• Bryan Stefek- Medical School at New York Medical College
• Leona Leung- Medical School at the University of West Virginia
• Nicky Stephenson- PhD student in Chemistry at the University of Wisconsin-Madison
• Dr. Mike MaCauley- Graduate of Penn State Medical School at Hershey
• Chris Roessler- PhD student in Biochemistry at the University of Arizona
• Mark Hedglin- Graduate of the Chemical Biology program at the University of Michigan
• Sam Oliver- PhD student in Biochemistry, University of Wisconsin-Madison
• Keris KrennHrubec- MPH student at the University of Michigan
• Colleen O'Loughlin- PhD student in Molecular Biology at Princeton
• Dr. Mike Clarke- Graduate of the University of Minnesota Medical School
• Dr. Sarah Boyce- Graduate of the Chemical Biology program at UCSF

Selected Publications

(*IC undergraduates)

Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, Grueter CA, Lim H, Saunders LR, Stevens RD, Newgard CB, Farese RV Jr, de Cabo R, Ulrich S, Akassoglou K, Verdin E.   "Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor."  Science. 2013 Jan 11;339(6116):211-4 link

Magadalena Karolczak-Bayatti, Michele Sweeney, Joanna Cheng, Lydia Edey, Stephen C. Robson, Scott M. Ulrich, Achim Treumann, Michael J. Taggart, and G. Nicholas Europe-Finner   "Acetylation of heat shock protein 20 (Hsp20) regulates human myometrial activity" J. Biol. Chem.  2011 doi: 10.1074/jbc.M111.278549 link

Tao Su, David M. Bryant, Frédéric Luton, Marcel Vergés, Scott M. Ulrich, Kirk C. Hansen, Anirban Datta, Dennis J. Eastburn, Alma L. Burlingame, Kevan M. Shokat Keith E. Mostov   "A kinase cascade leading to Rab11-FIP5 controls transcytosis of the polymeric immunoglobulin receptor" Nature Cell Biology 2010 DOI: doi:10.1038/ncb2118

Swem L, Swem D, O'Loughlin C*, Gatmaitman R*, Ulrich SM, Bassler B.  A Quorum Sensing Antagonist that Targets Both Membrane-Bound and Cytoplasmic Receptors Controls Bacterial Pathogenicity  Molecular Cell  35 (2) 143-153, 31 July 2009 link 

Oehme I, Deubzer HE, Wegener D, Pickert D, Linke J, Hero B, Kopp-Schneider A, Westermann F, Ulrich SM, von Deimling A, Fischer M, and Olaf Witt. "Histone Deacetylase 8 in NeuroblastomaTumorigenesis" Clinical Cancer Research 91 15(1) January 1, 2009 link

Ulrich SM "Chemistry and Roles of Protein Kinases and Dephosphorylases" 2007 Wiley Encyclopedia of Chemical Biology link

KrennHrubec K*, Marshal B, Hedglin M*, Verdin E and Ulrich SM. "Design and Evaluation of Linkerless Hydroxamic Acids and Selective HDAC8 Inhibitors" 2007 March 30 Bioorganic and Medicinal Chemistry Letters link

        ***this paper was one of the 50 most cited papers in BMCL between 2003-2010***

Ulrich SM, Kenski DM, Shokat KM. "Engineering a 'methionine clamp' into Src family kinases enhances specificity toward unnatural ATP analogues"  Biochemistry. 2003 Jul 8;42(26):7915-21.

Ulrich SM, Sallee NA, Shokat KM. "Conformational restraint is a critical determinant of unnatural nucleotide recognition by protein kinases"  Bioorg Med Chem Lett. 2002 Nov 4;12(21):3223-7.

Ulrich S, Shokat K. "Green fluorescent protein-based protein kinase biosensor substrates" Methods Mol Biol. 2002;183:275-85

Bradley, Alexander Z.; Ulrich, Scott M.; Jones, Maitland, Jr.; Jones, Stephanie M.  "Teaching the Sophomore Organic Course without a Lecture. Are You Crazy?"  Journal of Chemical Education 2002, 79, 514. link

Bishop A, Buzko O, Heyeck-Dumas S, Jung I, Kraybill B, Liu Y, Shah K, Ulrich S, Witucki L, Yang F, Zhang C, Shokat KM. "Unnatural ligands for engineered proteins: new tools for chemical genetics"  Annu Rev Biophys Biomol Struct. 2000;29:577-606

Grant R. Krow, Osbert H. Cheung, Zilun Hu, Qiuli Huang, John Hutchinson, Nian Liu, Kevin T. Nguyen, Scott Ulrich, Jing Yuan, Yushi Xiao, Donna M. Wypij, Fangming Zuo, Patrick J. Carroll.  "Nitrogen-bridge homoepibatidines: syn-6 and syn-5-(chloro-3-pyridyl) isoquinuclidines" Tetrahedron 1999; (55) 7747-7756.

Presentations

1. "Chemical Inhibition of Cell-Cell Communication in Bacteria" Mount Holyoke College, April 2011
2. "Chemical Inhibition of Cell-Cell Communication in Bacteria" Hobart and William Smith Colleges, 4/30/09
3. "Chemical Inhibition of Quorum Sensing Signaling in Chromobacterium violaceum" SUNY School of Environmental Science and Forestry, 2/27/09
4. "Chemical Inhibition of Bacterial Quorum Sensing" Colby College, 9/15/07
5. "Chemical Genetic Analysis of Histone Deacetylation" Hobart and William Smith Colleges, 9/22/05
6. "Peer-led, problem-based learning in organic chemistry", National ACS meeting, Phila PA, August 2004

By Ithaca College undergraduates:

1. Leah Graham "Design and synthesis of photo-crosslinking analogs of 968, a Glutaminase C inhibitor" NCUR 2012
2. Kevin Litwin and James Annand " Design and synthesis of aza-analogs of terpene synthase carbocation intermediates" NCUR, March 2012
3. Cornell Conca and Leah Graham "Chemical inhibition of bacterial quorum sensing" NCUR, April 1 2011.
4. Bryan Stefek "Characterization of toxic factors regulated by quorum sensing in Chromobacterium violacium" Rochester section of the American Chemical Society, April 2009
5. Colleen O'Loughlin "Design and synthesis of electrophilic LuxS inhibitors" ACS National Meeting, Chicago, March 2007
6. Keris KrennHrubec "Design and Evaluation of Linkerless Hydroxamic Acids and Selective HDAC8 Inhibitors" ACS National Meeting, Chicago, March 2007
7. Colleen O'Loughlin: "Peptidoglycan Deacetylase 'PgdA' as a New Antibiotic Drug Target" West Nottingham Academy, May 2006
8. Keris KrennHrubec: "Development of HDAC8-selective inhibitors" Ithaca College Whalen Symposium, April 2006.
9. Nicky Stephenson and Mike MaCauley: "LuxS as an antibacterial drug target." National ACS Meeting, San Diego March 2005
10. Mark Hedglin: "Engineering drug sensitive HDAC alleles" National ACS Meeting, San Diego March 2005
11. Nicky Stephenson: "LuxS as an antibacterial drug target." Rochester Academy of Sciences
    November 2003.
12. Chris Roessler: "Development of allele-specific histone deacetylase inhibitors." C-STEP State Meeting, Lake George, NY, April 2004.