Past Fellows

Kerry Bauer

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B.S. 2009, College of Saint Benedict/St. John’s University, St. Joseph, MN
Ph.D. 2014, Biochemistry, University of Notre Dame
Dissertation: Using Quantitative Transcriptomic and Proteomic Methodologies to Interrogate Biomarkers in Colon Cancer
Discipline: Biochemistry
Mentor: Amanda Hummon
CBBI Fellow: 2011-2014
Current Position: Postdoctoral Fellow, National Institute of Standards and Technology

Research Project:
Kerry interrogated the effect of a microRNA cluster on the colon cancer proteome and transcriptome. She used mass spectrometry, microarrays, RT-PCR and RNA interference to investigate the role of these antitumorigenic microRNAs. Kerry has completed a research internship with Dr. Lingjun Li (School of Pharmacy, University of Wisconsin-Madison) to learn quantitative chemical labeling strategies for proteomics.

Honors:

  • College of Saint Benedict Chemistry Achievement Award (2006)
  • Epsilon Sigma, Omega Chapter National Catholic Honor Society (2008)
  • Graduated with summa cum laude honors (College of Saint Benedict, 2009)

Publications:

  • Bauer, K. M.; Hummon, A. B.; Buechler, S. Right-side and left-side colon cancer follow different pathways to relapse. Mol Carcinog. 2012, 51:411-421.
  • Bauer, K.M.; Lambert, P. A.: Hummon, A.B. Comparative label-free LC-MS/MS analysis of colorectal adenocarcinoma and metastatic cells treated with 5-fluorouracil. Proteomics 2012, 12(12), 1928-1937.
  • Bauer, K.M.; Hummon, A.B.; Effects of the miR-143/-145 microRNA cluster on the colon cancer proteome and transcriptome. J. Proteome Res. 2012, 11, 4744-4754.
  • Weston, L.A.; Bauer, K.M.; Hummon, A.B.; Comparison of bottom-up proteomic approaches for LC-MS analysis of complex proteomes. Ana. Methods 2013, 5(18).
  • Weston, L.A.; Bauer, K.M.; Skube, S.B.; Hummon, A.B.; Selective, bead-based global peptide capture using a bifunctional cross-linker. Anal. Chem. 2013, 85, 10675-10679.
  • Bauer, K.M.; Watts, T.N.; Buechler, S.; Hummon, A.B.; Proteomic and functional investigation of the colon cancer relapse-associated genes NOX4 and ITGA3. J. Proteome REs. 2014, 13, 4910-4918.

Jill Bouchard

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B.S. 2009, University of Montana, Missoula, MT
Ph.D., 2014, Biochemistry, University of Notre Dame
Dissertation: Ensemble Interpretation of Domain Mobility in Modular Protein PIN1 by NMR and Molecular Dynamics
Discipline: Biochemistry
Mentor: Jeffrey Peng
CBBI Fellow: 2011-2014
Current Position: Postdoctoral Fellow, St. Jude Children’s Research Hospital

Research Project:
Jill investigated how interdomain motion affects the function of human Pin1, a peptidyl-prolyl isomerase involved in mitotic regulation. Pin1 contains two domains: a WW domain that binds specific phosphorylated substrates, and a PPIase domain that catalyzes substrate isomerization. Her goal was to define the crosstalk between these domains via the orientation and dynamic information contained in residual dipolar couplings. Jill’s cross-disciplinary work wasl be in the lab of Dr. David Case at Rutgers University to produce a complete picture of Pin1’s functional dynamics by using computational approaches to integrate multiple experimental parameters reporting on different timescales.

Honors:

  • Outstanding Senior in Chemistry (2009)
  • Montana Integrative Learning Experience for Students (MILES) Internship & Fellowship (2008)
  • Lien Undergraduate Fellowship (2008)
  • John D Sullivan Memorial Chemistry Scholarship (2006)
  • Montana University System (MUS) Scholarship (2004-2007)

Publications

  • Wilson, K.A.; Bouchard, J.J.; Peng, J.W.; Interdomain interactions support interdomain communication in human Pin1. Biochemistry 2013, 52 (40), 6968-6981.

Esther Braselmann

Esther Braselmann

Diplom. Biochemistry, 2009, University of Bielefeld, Germany
Ph.D, Biochemistry, 2014, University of Notre Dame
Dissertation: Investigating the Secretion of Folding Mechanism of a Beta-Sheet Rich Virulence Protein
Discipline: Biochemistry
Mentor: Patricia Clark
CBBI Fellow: 2010-2014
Current Position: Postdoctoral Fellow, University of Colorado, Boulder

Research Project:
Esther characterized the structural features of the stalled outer membrane secretion intermediate to determine whether the passenger domain crosses the outer membrane through its own porin domain or association to a non-autotransporter porin complex. She incorporated unnatural amino acids in the passenger and porin domains in vivo, isolates the complex, and after digestion identifies the cross-linked peptides by mass spectrometry. She conducted a research internship at the Franklin and Marshall College to learn synthetic methods to produce novel cross-linkers and optimize incorporation of unnatural amino acids into proteins.

Honors:

  • DAAD Fellowship, 2007

Publications:

  • Renn, J. P.; Junker, M.; Besingi, R. N.; Braselmann, E.; Clark, P. L. ATP-Independent Control of Autotransporter Virulence Protein Transport via the Folding Properties of the Secreted Protein. Chem Biol. 2011 Dec 28. [Epub ahead of print]

Katherine M. Byrd

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B.S. 2008, Xavier University, New Orleans, LA
Discipline: Chemistry
Mentor: Paul Helquist

Publications:

  • Cosner, C. C.; Cabrera, P. J.; Byrd, K. M.; Thomas, A. M.; Helquist, P. Selective oxidation of benzylic and allylic alcohols using Mn(OAc)3/catalytic 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. Org Lett. 2011, 15, 2071-3.

Cheng Ji

Cheng Ji

B.S. Chemistry 2007, Nanjing University, People’s Republic of China
Discipline: Organic Chemistry
Mentor: Marvin Miller
CBBI Fellow: 2010-2011
Current Position: Ph.D. Candidate, University of Notre Dame

Research Project:
Cheng is utilizing the “Trojan Horse” approach to synthesize derivatives of phenolic propionic acid as linkers between siderophores (iron-chelating agents) and antibiotics. He is also using different linkers to prepare drug conjugates of the siderophore pyoverdine as novel antipseudomonal agents. He conducted a research internship with Prof. Ian Lamont in the Biochemistry Department at the University of Otago, New Zealand, to carry out biosynthesis of pyoverdines, including bacteria culture, isolation, purification, and characterization of pyoverdine, and bioassays against P. aeruginosa (inhibition assays, MIC, mutants isolation).

Honors:

  • Third Prize of People’s Scholarship, 2003
  • Second Prize of People’s Scholarship, 2004
  • First Prize, Specialty Scholarship, 2005
  • Excellent Bachelor Thesis, 2007

Publications:

  • Ji, C.; Miller, M. J. Cyclopropanation of Nitroso Diels-Alder Cycloadducts and Application to the Synthesis of a 2’,3’-Methano Carbocyclic Nucleoside. Tet. Lett 2010, 51, 3789-3791.
  • Wu, D. H.; Ji, C.; Li, Y. Z.; Yan, H. A Novel Dinuclear Ruthernium(I)/Ruthernium(III) Half-sandwich Complex Contaiining Two Chelating 1,2-Dicarba-closo-dodecaborane-1,2-dithiolate Ligands and its Reactivity with Alkynes. Organometallics 2007, 26, 1560-1562.
  • Zhou, X.; Ji. C.; Fu, J.; Li, Y. G. Obacunone. Acta Crystal. E Struct Rep Online 2006, 62, O5544-O5546.

Mary Cloutier

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B.S. Biochemistry 2008, University of Maine, Orono
Discipline: Biological Sciences
Mentor: Kasturi Haldar

Research Project:
Mary is studying the binding of cholesterol to Neimann Pick Type C-1. Using docking simulations of cholesterol to the N_-terminal domain of NPC-1, she found that the isooctyl sidechain buried conformation was more energetically favorable than the 3beta-hydroxyl group buried conformation. She will also conduct NMR studies using recombinant NPC1-_N-terminal domain protein to determine the relevance in vitro, as well as using cholesterol binding assays. Mary’s cross-disciplinary training consists of computational studies with Prof. Jesus Izaguirre and NMR studies with Prof. Jeff Peng. In addition, she plans a research internship at Washington University School of Medicine to learn techniques for the purification and analysis of oxysterols and cholesterol to understand the trafficking defects contributing to Niemann Pick Type C disease.

Honors:

  • Biology Book Award
  • Member, National Society of Collegiate Scholars, 2004
  • Member, Phi Mu Epsilon Honors Society, 2007
  • Cum laude graduate, 2008

Erin Cole

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B.S. Chemistry and Biochemistry 2007, Drake University, Des Moines, IA
Discipline: Organic Chemistry
Mentor: Bradley Smith
CBBI Fellow: 2009-2011
Current Position: Ph.D. Candidate, University of Notre Dame

Research Project:
Erin is synthesizing multivalent fluorescent probes for imaging of damaged bone. Repetitive loading and stress results in microdamage to bone tissue that leads to increased susceptibility to fractures. Conventional methods for imaging and quantifying of microdamage are invasive and destructive, leading to limited medical applications. She is currently working in collaboration with the Ryan K. Roeder laboratory in the Department of Aerospace and Mechanical Engineering at the University of Notre Dame. In this collaboration she is learning about microdamage and bone imaging. Her research is to synthesize and evaluate multivalent squaraine-rotaxanes probes and nanoparticles for imaging of microdamage.

Honors:

  • Dr. William Homer and Florence Coppock Chemistry Research Award, 2006
  • Department of Chemistry Outstanding Senior Award, Drake University, 2007
  • Drake Undergraduate Science Collaborative Research Grant, 2006
  • Beta Beta Beta Biological Honor Society

Publications:

  • Cole EL, Arunkumar E, Xiao S, Smith BA, Smith BD. Water-soluble, deep-red fluorescent squaraine rotaxanes. Org Biomol Chem. 2011 Dec 8. [Epub ahead of print]
  • Smith, B. A.; O’Neil, E. J.; Lamplins, A. J.; Johnson, J. R.; Lee, J.-J.; Cole, E.; Smith, B. D. Evaluation of fluorescent phosphatidylserine substrates for the aminophospholipid flippase in mammalian cells. J. Fluoresc. 2011, DOI 10.1007/s10895-011-0933-0, Online First.

Michelle Favila

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B.S. Biology and French 2005, Emory University, Atlanta, GA
Discipline: Biology
Mentor: Mary Ann McDowell

Research Project:
Michelle is identifying the gnes that are expressed in Leishmania major and Leishmania donovani to provide insight into the disease phenotypes observed. She is also conducting genetic analysis of the biosynthesis of the lipophosphoglycan on the parasite surface to elucidate factors important for parasite virulence. She conducted a research internship with Prof. Steven Beverley in the Department of Molecular Microbiology at Washington University School of Medicine and learned double targeted gene replacement techniques to generate two L. major null mutant parasites lacking LPG1 and LPG2 genes. She conducted a second internship in the laboratory of Prof. Salvatore Turco, Department of Molecular and Cellular Biochemistry at the University of Kentucky to isolate and identify the lipophosphoglycan structures.

Honors:

  • Post baccalaurate NIH fellowship, 2005
  • Post baccalaurate NIH fellowship, 2006

Publications:

  • Carter, C.; Favila, M.; Polando, R.; Bogard, K.; Yadev, M.; McDowell, M. The Role of Complement Receptor 3 in Leishmania-induced Macrophage Signaling Modulation. submitted

Rosanne Frederick

frederick

B.S. Biochemistry 2006, University of Texas, Arlington, TX
Discipline: Biochemistry
Mentor: Jennifer Dubois
CBBI Fellow: 2008-2011
Current Position: Ph.D. Candidate, University of Notre Dame

Research Project:
Rosie’s project centers on the characterization of the mechanism, structure, and inhibition of siderophore-associated monooxygenases from pathogenic microbes. Rosie uses molecular biology, protein biochemistry, structural biology, and synthetic organic chemistry. She is currently carrying out a research internship at Marquette University to learn protein NMR techniques that will provide insightful approaches in understanding small molecule/protein interactions.

Honors:

  • McNair Scholar 2005-2006
  • Keytstone Symposia Scholarship– Antibiotics and Resistance: Challenges and Solutions (B3) Conference, funded by the Bill and Melinda Gates Foundation, February 2010

Publications

  • Frederick, R. E.; Mayfield, J. A.; DuBois, J. L. Iron Trafficking as an Antimicrobial Target. Biometals, 2009, DOI10.1007/s10534-009-9236-1 (online published April 7, 2009).
  • Mayfield, J. A.; Frederick, R. E.; Streit, B. R.; Wencewicz, T. A.; Ballou, D. P.; DuBois, J. L. Comprehensive Spectroscopic, Steady State, and Transient Kinetic Studies of a Representative Siderophore-Associated Flavin Monooxygenase.” J. Biol. Chem. 2010, 285, 30375-30388.
  • Frederick, R. E.; Mayfield, J. A.; DuBois, J. L. Protein-level regulation of O2 activation in biosynthetic flavin-dependent monooxygenases. J. Am. Chem. Soc., 2011, 133 (32), 12338–12341.

Major Gooyit

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B.S. Chemistry 2004, University of the Philippines
Discipline: Organic Chemistry
Mentors: Mayland Chang and Shahriar Mobashery

Research Project:
Major’s project involves the syntheses and evaluation of variants of SB-3CT, a selective gelatinase inhibitor that shows efficacy in animal models of cancer metastasis and stroke, with higher potency and increased metabolic stability. He uses organic synthesis, enzyme kinetics, MS/MS experiments for identification of metabolites, pharmacokinetics, gelatin zymography, in situ gelatin zymography, and histology. Major conducted a research internship with Prof. Irit Sagi in the Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel, to crystallize MMP-9 in complex with the inhibitors, as well as overexpress and purify MMP-9 E402A mutant enzyme. He conducted a second research internship with Prof. Zezong Gu in the Department of Pathology and Anatomical Sciences at the University of Missouri-Columbia to assess the in vivo efficacy of the inhibitors in mouse models of stroke and traumatic brain injury.

Honors:

  • B.S. Honors, 2004
  • Kaneb Outstanding Teaching Assistant Award, 2008
  • 1st Place Presentation, CBBI Retreat, 2009
  • Gordon Research Conference on Matrix Metalloproteinases Poster Award, 2011
  • Gordon Research Seminar on Matrix Metalloproteinases Discussion Leader, 2011

Publications:

  • Gooyit, M.; Lee, M.; Hesek, D.; Boggess, B.; Oliver, A.; Fridman, R.; Mobashery, S.; Chang, M. Synthesis, kinetic characterization and metabolism of diastereomeric 2-(1-(4-phenoxyphenylsulfonyl)ethyl)thiiranes as potent gelatinase inhibitors. Chem Biol Drug Design, 2009, 74, 535-546.
  • Gooyit, M.; Lee, M.; Schroeder, V. A.; Ikeji, M.; Suckow, M.; Mobashery, S.; Chang, M. Selective water-soluble gelatinase inhibitor prodrugs. J. Med. Chem., 2011, 54, 6676-6690.

Brandon Haines

Brandon Haines

B.S. Chemistry 2009, Grand Valley State University
Discipline: Organic Chemistry
Mentor: Olaf Wiest

Research Project:
Brandon is studying the mechanism of HMG-CoA reductase, an enzyme in the mevalonate pathway that produces cholesterol and other isoprenoids and the target of the cholesterol-lowering drugs statins. He uses Laue crystallography, organic chemistry, biophysics, and computational chemistry. He is currently conducting a research internship with Prof. Cynthia Stauffacher in the Department of Biological Sciences at Purdue University in structural biology. He uses site-directed mutagenesis and PCR to design and express a mutant form of HMG-CoA reductase, and then generate and resolve the crystal structure of the enzyme.

Honors:

  • Grand Valley State University Sophmore Chemistry Award, 2006
  • I Am Grand Valley Award, 2008

Publications:

  • Ngassa, F.; Lindsay, E.; Haines, B. The First Cu- and Amine-free Sonogashira-type cross-coupling in the C-6-Alkynylation of Protected 2’-Deoxyadenosine. Tetrahedron 2009, 65, 4085-4091.

Jessica Hornick

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B.S. Biology 2001, University of Illinois, Chicago, IL
Ph.D. Biological Sciences 2009, University of Notre Dame
Discipline: Biology
Mentor: Edward Hinchcliffe
CBBI Fellow: 2008-2009
Current Position: Postdoctoral Fellow, Northwestern University

Research Project:
Jessica’s project focused on analyzing mitotic spindle formation and the role of centrosomes. She used microsurgery, biophysical techniques, and chemical biology to analyze spindle assembly.

Honors:

  • Fisher Fellowship, 2004
  • Pollard Fellowship, 2007

Publications

  • Colliins, E. S.; Hornick, J. E.; Durcan, T. M.; Collins, N. S.; Archer, W.; Karanjeet, K. B.; Vaughan, K. T.; Hinchcliffe, E. H. Centrosome biogenesis continues in the absence of microtubules during prolonged S-phase arrest. J. Cell Physiol. 2010 May 10 {Epub ahead of print} PMID 20458743.
  • Hornick, J. E.; Karanjeet, K.; Collins, E. S.; Hinchcliffe, E. H. Kinesins to the core: The role of microtubule-based motor proteins in building the mitotic spindle midzone. Semin. Cell Dev. Biol. 2010, 21, 290-299.
  • Hornick, J.; Bader, J. R.; Tribble, E. K.; Breunig, J. S.; Halpin, E. S.; Vaughan, K. T.; Hinchcliffe, E. H. Live-cell analysis of mitotic spindle formation in taxol-treated cells. Cell Motil Cytoskeleton. 2008, 65, 595-613.
  • Durcan, T. M.; Halpin, E. S.; Rao, T.; Collins, N. S, Tribble, E. K.; Hornick, J. E.; Hinchcliffe, E. H. Tektin 2 is required for central spindle microtubule organization and the completion of cytokinesis. J. Cell Biol. 2008, 181, 595-603.
  • Walker, M.; Hjort, E.; Smith, S.; Hornick, J. E.; Hinchcliffe, E. H.; Hager, K. Toxoplasma gondi actively remodels the microtubule network in host cells. Microbes Infect. 2008, 10, 1440-1449.
  • Whyte, J.; Bader, J. R.; Tauhata, S.; Raycroft, M.; Hornick, J. E.; Pfister, K.K.; Lane, W. S.; Chang, G. K.; Hinchcliffe, E. H.; Vaughan, P. S.; Vaughan, K. T. Phosphorylation regulates targeting of cytoplasmic dynein to kinetochores during mitosis. J. Cell Biol. 2008, 183, 819-834.

Francis Insaidoo

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B.A. Biology and Chemistry 1999, St. John’s University, Collegeville, MN
M.S. Bioinformatics 2003, Georgia Institute of Technology, Atlanta, GA
Ph.D. Biochemistry 2010, University of Notre Dame
Discipline: Biochemistry
Mentor: Brian Baker
CBBI Fellow: 2007-2009
Current Position: Postdoctoral Fellow, Columbia University

Research Project:
Francis studied the influence of peptide dynamics on T cell receptor recognition, the type of immune response generated, and why certain peptide substitutions improve, while others abolish antigen specific recognition. He used NMR and molecular dynamics simulations to obtain atomic level information on the types of motion available to different peptides presented by class I MHC molecules. In addition, he developed a biosynthetic approach for the synthesis of isotopically labeled peptides and class I MHC proteins. Francis carried out an internship with Prof. David Kranz at the University of Illinois, Urbana-Champain, conducting cellular and molecular experiments using yeast display, flow cytometry, PCR, and immunohistochemistry to address how dynamics in the T-cell receptor influence recognition of antigen.

Honors:

  • Newman Scholar, 2003
  • Tower Award, 2003
  • Gordon Conference Grant Recipient, 2006

Publications

  • Davis-Harrison, R. L.; Insaidoo, F. K.; Baker, B. M. T Cell Receptor Binding Transition States and Recognition of Peptide/MHC. Biochemistry 2007, 46, 1840-1850.
  • Borbulevych, O.Y.; Insaidoo, F. K.; Baxter, T. K.; Powell, D. J. Jr.; Johnson, L. A.; Restifo, N. P.; Baker, B. M. Structures of MART-1(26/27-35) Peptide/HLA-A2 Complexes Reveal a Remarkable Disconnect between Antigen Structural Homology and T Cell Recognition. J Mol Biol. 2007, 372, 1123-36.
  • Armstrong, K. M.; Insaidoo, F. K.; Baker, B. M. Thermodynamics of T-cell receptor-peptide/MHC interactions: progress and opportunities. J Mol Recognit. 2008, 21, 275-287.
  • Insaidoo, F. K.; Zajicek, J.; Baker, B. M. A general and effective approach for NMR studies of peptide dynamics in class I MHC peptide binding grooves. Biochemistry 2009, 48, 9708-9710.
  • Aggen DH, Chervin AS, Insaidoo FK, Piepenbrink KH, Baker BM, Kranz DM. Identification and engineering of human variable regions that allow expression of stable single-chain T cell receptors. Protein Eng Des Sel. 2011, 24, 361-72.
  • Insaidoo FK, Borbulevych OY, Hossain M, Santhanagopolan SM, Baxter TK, Baker BM. Loss of T cell antigen recognition arising from changes in peptide and major histocompatibility complex protein flexibility: implications for vaccine design. J Biol Chem. 2011, 286, 40163-73.

Richard Kurker

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B.S. 2009, Providence College, Providence, RI
Discipline: Biochemistry
Mentor: Jennifer Dubois

Research Project:

Richard’s research focuses on HemQ, a protein in the CDE superfamily that is phylogenetically related to the well-characterized chlorite dismutase protein that converts chlorite to chloride and oxygen. HemQ is found exclusively in Gram-positive bacteria but does not respire chlorite, so the project is geared toward determining the function of the uncharacterized HemQ protein using techniques in biochemistry, molecular biology, and bioinformatics. Richard conducted a research internship in the laboratory of Prof. Eric Skaar at Vanderbilt University Medical Center in Nashville, TN, to gain experience with growing Staphylococcus aureus, produce genetic complementations for phenotype restoration, and prepare FLAG-tagged protein for use in in vivo immunoprecipitation.

Honors:

  • Genomics and Bioinformatics Fellowship (University of Notre Dame Eck Institute of Global Health) (2010)
  • Graduated with summa cum laude honors, Liberal Arts Honors Program, and Award for Highest GPA in Biochemistry (Providence College, 2009)
  • Rev. Frederick C. Hickey, O.P. Science Award for academic excellence in chemistry/biochemistry (Providence College, 2009)
  • First place poster prize at the MRSEC Summer Undergraduate Research Expo (University of Minnesota, 2008)

Publications:

Goblirsch B, Kurker RC, Streit BR, Wilmot CM, DuBois JL. Chlorite dismutases, DyPs, and EfeB: 3 microbial heme enzyme families comprise the CDE structural superfamily. J Mol Biol. 2011, 408, 379-98.

Joshua Lee

joshua_lee

B.S. Chemistry 2008, University of Minnesota, Twin Cities
Discipline: Organic Chemistry
Mentor: Paul Helquist and Olaf Wiest
CBBI Fellow: 2010-2011
Current Position: Ph.D. Candidate, University of Notre Dame

Research Project:
Joshua’s project involves the syntheses of derivatives of archazolids and iejimalides, potent inhibitors of vacuolar ATPase, which cause death in cancer cells. He uses computational methods to screen libraries of chiral catalysts for vinologous Mukaiyama aldol reactions and select selective asymmetric catalysts. He will then conduct a QSAR study to screen inhibitors; selective inhibitors will be synthesized and tested for biological activity in vitro. He conducted a research internship with Prof. V. Jo Davisson in the Department of Medicinal Chemistry and Molecular Pharmacology at Purdue University to learn and develop biochemical and cell biology techniques to test the iejimalides and other ATPase inhibitors for biological activity in yeast, human cancer cell lines, and xenograft models.

Honors:

  • Institute of Technology Honors Program
  • Heisig/Gleysteen Chemistry Summer Fellowship Program
  • Maroon Scholarship

Christine Monteleon

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B.S. Biology 2005, University of Michigan, Ann Arbor, MI
Ph.D. Biology 2011, University of Notre Dame
Discipline: Biology
Mentor: Crislyn D’Souza-Schorey
CBBI Fellow: 2008-2010
Current Position: Postdoctoral Fellow, University of Notre Dame

Research Project:
Christine studied the mechanisms of epithelial gland development and its altered regulation during tumor progression. She began interdisciplinary investigations into the properties of basement membrane with the University of Notre Dame Aerospace & Mechanical Engineering Department. She conducted a research internship with Prof. Sherry Voytik-Harbin in the Department of Biomechanical Engineering at Purdue University examining the physical and mechanical properties of extracellular matrix in response to epithelial morphogenesis.

Honors:

  • UMBS Scholarship, 2004
  • Reilly Fellowship, 2005
  • Reilly Fellowship, 2006
  • Warner-Lambert Fellowship, 2007

Publications

  • Begley, L.; Monteleon, C.; Shah, R. B.; Macdonald, J. W.; Macoska, J. A. CXCL12 overexpression and secretion by aging fibroblasts enhance human prostate epithelial proliferation in vitro. Aging Cell. 2005, 4, 291-298.
  • Moore, T. A.; Lau, H. Y.; Cogen, A.L.; Monteleon, C.; Strandiford, T. J. Anti-tumor necrosis factor-alpha therapy during murine Klebsiella pneumoniae bacteremia: increased mortality in the absence of liver injury. Shock. 2003, 20, 309-315.
  • Moore, T. A.; Perry, M. L.; Getsoian, A. G.; Monteleon, C. L.; Cogen, A. L.; Standiford, T. J. Increased mortality and dysregulated cytokine production in tumor necrosis factor receptor 1-deficient mice following systemic Klebsiella pneumoniae infection. Infect Immun. 2003, 71, 4891-4900.

Apryle O’Farrell

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B.S. Chemistry, Mathematics and Biology 2007, Waynesburg College, Waynesburg, PA
M.S. Chemistry 2011, University of Notre Dame
Discipline: Organic Chemistry
Mentor: Shahriar Mobashery
Current Position:

Research Project:
Apryle’s project focused on the design and synthesis of a new class of covalent inhibitors of bacterial DD-transpeptidases and DD-carboxypeptidases based upon an L-Ser-D-Ala dipeptide. Her studies involved computational chemistry to rank in silico a virtual library using QM/MM analysis of the active site, syntheses of a focused series of target compounds, evaluation of the microbiological activity, and enzyme kinetics with E. coli penicillin-binding proteins (PBPs).

Honors:

  • Eastern Analytical Symposium Undergraduate Research Award, 2006
  • American Chemical Society Analytical Chemistry Undergraduate Research Award, 2006
  • Indiana Clinical and Translational Science Institute Predoctoral Fellowship, 2010

Julia Philip

philip

B.S. Chemical Engineering 2006, Princeton University
M.S. Chemical Engineering 2007, Carnegie Mellon University
Discipline: Physical Chemistry
Mentor: Holly Goodson
CBBI Fellow: 2008-2010
Current Position: Ph.D. Candidate, University of Notre Dame

Research Project:
Julia’s research focuses on microtubule dynamics and the effect of plus end tracking proteins on tubulin polymerization. She uses cell biology, biophysics, light microscopy, fluorescence correlation spectroscopy, protein binding assay, and computational modeling. She completed a research internship in the Department of Biochemistry and Molecular Biology at Oklahoma State University learning yeast genetic manipulation.

Honors:

  • Sigma Xi, 2006
  • Nieuwland Fellowship, 2008

Publications

  • Philip, J.; Noel Dahl, K. Nuclear mechanotransduction: response of the lamina to extracellular stress with Implications in aging. J. Biomechanics, 2008, 41, 3164-3170.
  • Philip JT, Pence CH, Goodson HV. MTBindingSim: simulate protein binding to microtubules. Bioinformatics. 2012, 28, 441-3.

Kurt Piepenbrink

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B.A. Chemistry and German Literature 2005, Johns Hopkins University, Baltimore, MD
Ph.D. 2011, University of Notre Dame
Discipline: Biochemistry
Mentor: Brian Baker
CBBI Fellow: 2008-2010
Current Position: Postdoctoral Fellow, University of Maryland Medical Center

Research Project:
Kurt studies the structural and energetic basis for T-cell receptor with the complex of an antigen presenting molecule. He uses non-natural amino acids to test specific patterns of recognition, as well as double mutant cycles to probe the importance of specific side-chain interactions. Kurt conducted a research internship at the University of Cardiff to explore T-cell recognition of antigens through immunological assays and combinatorial peptide libraries with the aim of characterizing superagonist peptides to the A6 TCR and correlating their binding parameters with their immunological potency.

Honors:

  • Gordon Conference Grant Award 2007, 2008

Publications

  • Armstrong, K. M.; Piepenbrink, K. H.; Baker, B. M. Conformational Changes and Flexibility in T Cell Receptor Recognition of Peptide/MHC. Biochem. J., 2008, 415, 183-196.
  • Borbulevych, O. Y.; Piepenbrink, K. H.; Gloor, B. E.; Scott, D. R.; Sommese, R. F.; Cole, D. K.; Sewell, A. K.; Baker, B. M. T Cell Receptor Cross-reactivity Directed by Antigen-dependent Tuning of Peptide-MHC Molecular Flexibility. Immunity 2009, 31, 885.
  • Piepenbrink, K. H.; Gloor, B. E.; Armstrong, K. M.; Baker, B. M. Methods for Quantifying T cell Receptor Binding Affinities and Thermodynamics. Meth. Enzymol. 2009, 466, 359.
  • Piepenbrink, K. H.; Borbulevych, O. Y.; Sommese, R. F.; Clemens, J.; Armstrong, K. M.; Desmond, C.; Baker, B. M. Fluorine Substitutions in an Antigenic Peptide Selectively Modulate T-cell Receptor Binding in a Minimally Perturbing Manner. Biochem. J. 2009, 423, 353.
  • Aggen DH, Chervin AS, Insaidoo FK, Piepenbrink KH, Baker BM, Kranz DM. Identification and engineering of human variable regions that allow expression of stable single-chain T cell receptors. Protein Eng Des Sel. 2011, 24, 361-72.
  • Borbulevych OY, Piepenbrink KH, Baker BM. Conformational melding permits a conserved binding geometry in TCR recognition of foreign and self molecular mimics. J Immunol. 2011, 186, 2950-8.
  • Aggen DH, Chervin AS, Schmitt TM, Engels B, Stone JD, Richman SA, Piepenbrink KH, Baker BM, Greenberg PD, Schreiber H, Kranz DM. Single-chain VαVβ T-cell receptors function without mispairing with endogenous TCR chains. Gene Ther. 2011 Jul 14. doi: 10.1038/gt.2011.104. [Epub ahead of print]
  • Scott DR, Borbulevych OY, Piepenbrink KH, Corcelli SA, Baker BM. Disparate degrees of hypervariable loop flexibility control T-cell receptor cross-reactivity, specificity, and binding mechanism. J Mol Biol. 2011 Dec 2;414(3):385-400.

Jonathan Renn

Renn

B.S. Biochemistry 2004, Benedictine University, Lisle, IL
Ph.D. Biochemistry 2010, University of Notre Dame
Discipline: Biochemistry
Mentor: Patricia Clark
CBBI Fellow: 2007-2008
Current Position: Postdoctoral Fellow, Northwestern University

Research Project:
Jonathan studied the folding and secretion of the autotransporter virulence protein Pet. He conducted in vitro folding and stability experiments to understand how Pet folds. In vivo studies of Pet secretion and folding were performed in order to understand the biogenesis of this protein.

Publications:

  • Renn, J. P.; Clark, P. L. A conserved stable core structure in the passenger domain β-helix of autotransporter virulence proteins. Biopolymers. 2008, 89, 420-427.
  • Renn JP, Junker M, Besingi RN, Braselmann E, Clark PL.ATP-Independent Control of Autotransporter Virulence Protein Transport via the Folding Properties of the Secreted Protein. Chem Biol. 2011 Dec 28. [Epub ahead of print]

Douglas Rice

rice

B.A. 2010, Willamette University, Salem, OR
Discipline: Biochemistry
Mentor: Bradley Smith

Research Project:

Doug’s project involves the fabrication of dye-doped particles for use in the optical imaging of disease. He uses squaraine rotaxane dyes which can emit fluorescent and chemiluminescent light in the near-infrared region. He has recently been exploring a variety of particle platforms including micelles, polystyrene particles and liposomes and their ability to target cell death, cancer and bacterial infection in vivo using mouse models. Doug will conduct internships at the University of Massachusetts Amherst and MIT to study new polymeric systems for in vivo dye delivery and synthetic strategies for adhering targeting groups to the surface of nanoparticles.

Honors:

  • Kaneb Outstanding Graduate Student Teacher Award, Notre Dame University, 2011
  • Lily Grant Recipient, Willamette University, 2009
  • Florian Von Eschen Chemistry Scholarship Recipient, Willamette University, 2009
  • Paul M Duell Chemistry Scholarship Recipient, Willamette University, 2008

Ian Sander

sander

B.S. Biochemistry 2006, Miami University, Oxford, OH
Discipline: Biochemistry
Mentor: Patricia Clark
CBBI Fellow: 2008-2010
Current Position: Ph.D. Candidate, University of Notre Dame

Research Project:
Ian’s research investigates the effect of rare codon clusters on protein folding. He uses computational and bioinformatic methods, biophysics, biochemical assays, and molecular biology. He conducted a research internship at the University of California-San Francisco and learned how to clone synthetic genes into any locus in the bacterial chromosome.

Publications

  • Evans, M. S.; Sander, I. M.; Clark, P. L. Co-translational folding promotes β-helix formation and avoids Aggregation in vivo. J Mol. Biol. 2008, 283, 683-692.

Daniel Scott

Daniel Scott

B.S. Chemistry 2002, University of Florida, Gainesville, FL
B.S. M.Ed. 2003, University of Florida, Gainesville, FL
_Ph.D. Chemistry, 2012, University of Notre Dame
Discipline: Chemistry
Mentor: Dr. Brian M. Baker
CBBI Fellow: 2010-2012
Current Position: Research Chemist, National Institute of Standards and Technology, Washington, D. C.

Research Project:
Daniel’s research addresses how conformational dynamics of T-cell receptor (TCR) proteins influence their cross-reactivity to determine the mechanisms that TCRs use to bind their antigenic peptide/MHC complexes. His research may contribute to the optimization of vaccine design for autoimmune diseases and cancer. Daniel uses time-resolved fluorescence anisotropy and molecular dynamics simulations. He is currently conducting a research internship with Prof. Steven Corcelli at the University of Notre Dame in computational chemistry to learn molecular dynamics simulations.

Publications

  • Borbulevych, O. Y.; Piepenbrink, K. H.; Gloor, B. E.; Scott, D. R.; Sommese, R. F.; Cole, D. K.; Sewell, A. K.; Baker, B. M. T Cell Receptor Cross-reactivity Directed by Antigen-dependent Tuning of Peptide-MHC Molecular Flexibility. Immunity 2009, 31, 885.
  • Scott, D. R.; Borbulevych, O. Y.; Piepenbrink, K. H.; Corcelli, S. A.; Baker, B. M. Disparate degrees of hypervariable loop flexibility control T-cell receptor cross-reactivity, specificity, and binding mechanism. J Mol Biol. 2011, 414, 385-400.
  • Baker, B. M.; Scott, D. R.; Blevins, S. J.; Hawse, W. F., Structural and dynamic control of T-cell receptor specificity, cross-reactivity, and binding mechanism. Immunol Rev. 2012 Nov;250(1):10-31.
  • Scott, D. R.; Vardeman, C. F. 2nd; Corcelli, S. A.; Baker, B. M., Limitations of the time-resolved fluorescence suggested by molecular simulations: assessing the dynamics of T-cell receptor binding loops. Biophys J. 2012 Dec 19;103(12):2532-2540.
  • Piepenbrink, K. H.; Blevins, S. J.; Scott, D. R.; Baker, B. M., The basis for limited specificity and MHC restriction in a T-cell receptor interface. Nat Commun. 2013 Jun 5;4:1948.
  • Cole, E. K.; Sami, M.; Scott, D. R.; Rizkallah, P. J.; Borbulevych, O. Y.; Todorov, P. T.; Moysey, R. K.: Jakobsen, B. K.; Boulter, J. M.; Baker, B. M.; Yi, Li, Increased peptides contacts govern high affinity binding of a modified TCR whilst maintaining a native pMHC docking mode. Front Immunol. 2013 Jun 26;4:168.
  • Scott, D. R.; Borbulevych, O. Y.; Piepenbrink, K. H.; Corcelli, S. A.; Baker, B. M., Distinct energy landscapes of a T-cell receptor’s hypervariable loops contribute to cross-reactivity, specificity, and MHC restriction, Submitted to J. Mol. Biol.

Jordan Scott

Jordan Scott

B.Sc. Biology 2002, Calvin College
Discipline: Biochemistry
Mentor: Robert Stahelin

Research Project:
Jordan’s research focuses in solving the molecular mechanisms of hijacking of the human Nedd4 family of proteins by an array of viruses. She uses biochemistry, biophysics, cell biology, and computational biology to understand the molecules and mechanisms that control new virion formation from human cells, to provide lipidome and proteome of virions to help identify targets for antiviral therapy. She conducted a research internship with Prof. Sirano Dhe-Paganon in the Structural Genomics Consortium at the University of Toronto to train in structural biology to crystallize the Ebola matrix protein VP40 with host-interacting proteins.

Honors:

  • Roger K. Bretthauer Biochemistry Teaching Award, 2010
  • MIAA Academic Honor Roll, 2007
  • Comenius Scholar/Intern, Cherry Street Health Services
  • NCAA Division III Two-Time Academic All American, 2007
  • King’s Christian Collegiate Gold Award for Academic Excellence, 2005

Publications

  • He, J.; Scott, J. L.; Heroux, A.; Roy, S.; Lenoir, M.; Overduin, M.; Stahelin, R. V.; Kutateladze, T. G. Molecular basis of phosphatidylinositol 4-phosphate and ARF1 GTPase recognition by the FAPP1 pleckstrin homology (PH) domain. J Biol Chem. 2011, 286, 18650-7.
  • He, J.; Gajewiak, J.; Scott, J. L.; Gong, D.; Ali, M.; Best, M. D.; Prestwich, G. D.; Stahelin, R. V.; Kutateladze, T. G. Metabolically stabilized derivatives of phosphatidylinositol 4-phosphate: synthesis and applications. Chem Biol. 2011 Oct 28;18(10):1312-9.
  • Scott, J. L.; Musselman, C. A.; Adu-Gyamfi, E.; Kutateladze, T. G.; Stahelin, R. V. Emerging methodologies to investigate lipid-protein interactions. Integr Biol (Camb). 2012 Feb 10. [Epub ahead of print]

Yao Shen

shen

B.S. Biology 2004, Nanjing University, People’s Republic of China
M.S. Microbiology 2006, Nanjing University, People’s Republic of China

Ph.D. Chemistry 2011, University of Notre Dame
Discipline: Organic Chemistry
Mentor: Dr. Olaf Wiest
CBBI Fellow: 2009-2011
Current Position: Associate Research Scientist, Columbia University

Research Project:
Yao’s project involved metabolic network reconstruction to predict essential enzymes as antibiotic drug targets. She used computational methods to study the interactions of enzymes with small molecules. She identified nine compounds that inhibit fathy acid synthesis (FAS). Yao conducted a research internship in the Department of Pathology, University of Pittsburgh. She tested 26 compounds predicted as inhibitors of FAS, using the fatty acid elongation, agar diffusion, and liquid culture assays.

Honors:

  • Travel Grant, Gordon Conference on Computer Aided Drug Design, Boston, 2009
  • Excellent Poster Award, Theory and Application of Computational Chemistry International Conference, 2008
  • Second Prize Forum of Sciences and Arts, Nanjing University, 2003
  • People’s Fellowship, Nanjing University, 2003
  • People’s Fellowship, Nanjing University, 2001

Publications:

  • Shen, Y.; Liu, G.; Estiu, G.; Isin, B.; Ahn, Y. Y.; Lee, D. S.; Barabasi, A. L.; Kapatral, V.; Wiest, O.; Oltvai, Z. N. Blueprint for Antimicrobial Hit Discovery Targeting Metabolic Networks. Proc. Natl. Acad. Sci. 2010, 107, 1082-1087. Highlighted in Nature, 2010, 463, 139.
  • Filippakopoulos, P.; Qi, J.; Picaud, S.; Shen, Y.; Smith, W. B.; Keates, T.; Morse, E. M.; Fedorov, O.; Hickman, T. T.; Philpott, M.; West, N.; Cameron, M. J.; Heightman, T.; Kung, A.; French, C. A.; Wiest, O.; Knapp, S.; Bradner, J. E. Selective Inhibition of BET Bromodomains. Nature, 2010, doi:10.1038/nature09504.
  • Ge, H. M.; Shen, Y.; Zhu, C. H.; Tan, S. H.; Ding, H.; Song, Y. C.; Tan, R. X. Penicidones A-C, Three Cytotoxic Alkaloidal Metabolites of an Endophytic Penicillium sp. Phytochemistry, 2008, 69, 571-576.

Bryan Smith

smith

B.S. Biochemistry 2007, DePauw University, Greencastle, IN
Ph.D. Biochemistry, 2012, University of Notre Dame
Discipline: Biochemistry
Mentor: Dr. Bradley D. Smith
CBBI Fellow: 2008-2011
Current Position: Postdoctoral Fellow, UCLA School of Medicine

Research Project:
Bryan’s research focuses on selective cell delivery via the phosphatidylserine receptor and cancer imaging using near IR probes. He uses biochemistry, chemistry, and biology. He conducted a research internship with Profs. Samuel Achilefu and David Piwnica-Worms at Washington University in St. Louis and learned tumor imaging. He carried out a second research internship with Dr. James Wheeler in Radiation Oncology at the Goshen Center for Cancer Care to evaluate the ability of a fluorescent probe as an in vivo imaging probe for cancer cell death due t radiotherapy. He completed a third research internship with Dr. Clemens Lowik in the Department of Endocrinology at Leiden University Medical Center, Netherlands to learn in vivo imaging cell death of their nerar-IR probe of stroke and other forms of braininjury in mice.

Publications:

  • Smith, B. A.; Akers, W. J.; Leevy, W. M.; Lampkins, A. J.; Xiao, S.; Wolter, W.; Suckow, M. A.; Achilefu, S.; Smith, B. D. Optical imaging of mammary and prostate tumors in living animals using a near-infrared zinc(II)-dipicolylamine probe. J. Am. Chem. Soc. 2010, 132, 67-69.
  • Smith BA, Gammon ST, Xiao S, Wang W, Chapman S, McDermott R, Suckow MA, Johnson JR, Piwnica-Worms D, Gokel GW, Smith BD, Leevy WM. In vivo optical imaging of acute cell death using a near-infrared fluorescent zinc-dipicolylamine probe. Mol Pharm. 2011 Apr 4;8(2):583-590.
  • Smith BA, Xiao S, Wolter W, Wheeler J, Suckow MA, Smith BD. In vivo targeting of cell death using a synthetic fluorescent molecular probe. Apoptosis. 2011 Jul;16(7):722-31.
  • Smith BA, O’Neil EJ, Lampkins AJ, Johnson JR, Lee JJ, Cole EL, Smith BD. Evaluation of fluorescent phosphatidylserine substrates for the aminophospholipid flippase in Mammalian cells. J Fluoresc. 2012 Jan;22(1):93-101.
  • Cole EL, Arunkumar E, Xiao S, Smith BA, Smith BD. Water-soluble, deep-red fluorescent squaraine rotaxanes. Org Biomol Chem. 2012 Aug 14;10(30):5769-5773.
  • McDermott, R.; Smith, B.A.; Leevy, W. M. Fluorescence imaging of cancer in live animals: Time to get exscited. Int Labmate, 2010, 35, 54-55.
  • Gammon, S. T.; Smith, B. A.; Suckow, M.A.; Loechner, M.; Leevy, W.M. Short review of advances in fluorescence imaging of cancer biology and relevant pathways. Oncol News, 2010,5, 46-48
  • Smith, B. A.; Akers, W. J.; Leevy, W. M.; Achilefu, S.; Smith, B. D. In vivo optical imaging of prostate tumors in Lobund-Wistar rats using a near-infrared fluorescence probe for anionic membranes. Carestream Health Scientific Insights, in press.
  • Smith, B. A.; Leevy, W. M. Spectral unmixing of indocyanide green in the vascular network of a leaf. Carestream Health Scientific Insights, in press.
  • Smith, B. A.; Xie, B.; Van Beek, E. R.; Que, I.; Blankevoort, V. Xiao, S.; Cole, E. L.; Hoehn, M.; Kaiizel, E. L.; Löwik, C. W.; Smith, B. D., Multicolor fluorescence imaging of traumatic brain injury in a cryolesion mouse model. ACS Chem Neurosci. 2012 Jul 18;3(7):530-537.
  • Smith, B. A.; Smith, B. D., Biomarkers and molecular probes for cell death imaging and targeted therapeutics. Bioconjug Chem. 2012 Oct 17;23(10):1989-2006.
  • Smith, B. A.; Harmatys, K. M.; Xiao, S.; Cole, E. L.; Plaunt, A. J.; Wolter, W.; Suckow, M. A.; Smith B. D., Enhanced cell death imaging using multivalent zinc(II)-bis(dipicolylamine) fluorescent probes. Mol Pharm. 2013 Sep 3;10(9):3296-3303.

Jennifer Starner-Kreinbrink

starner_cbbi_at_448

B.A. 2008, Wartburg College, Waverly, IA
Discipline: Biochemistry
Mentor: Patricia Clark

Research Project:
Jennifer’s research focuses on understanding the folding and aggregation propensity of parallel β-helices. Parallel β-helices have been identified in many proteins that serve as toxins, virulence factors and allergens, and consist of a geometrically regular all-β-domain. Aggregation of β-helices is especially intriguing as the β-helix has been used as one model for amyloid structure. However, the majority of β-helical proteins are soluble, suggesting that these proteins contain additional sequence or structural elements to help prevent the formation of insoluble amyloid-like fibers. Jennifer is working on identifying these sequence or structural elements and determining how they control aggregation. In addition, she is also studying how aggregation of β-helices can serve a functional purpose. She completed her internship at the University of Florida with Professor Jorge A. Giron to investigate the assembly of macromolecular rope-like aggregates of EspP, a β-helical autotransporter from E. coli. Her research combines computational biology, biochemical and biophysical experimental techniques, and biological assays.

Honors:
*Received the Emil T. Hoffman Graduate Teaching Award for excellence in teaching by a teaching assistant in the first year program- 2009/2010
*Selected for an oral presentation at the Midwest Conference on Protein Folding, Assembly, and Molecular Motions – April 2010

Publications:

  • Bryan AW Jr, Starner-Kreinbrink JL, Hosur R, Clark PL, Berger B. Structure-based prediction reveals capping motifs that inhibit β-helix aggregation. PNAS 2011, 108(27): 11099-11104.

Lindsay Sweet

Sweet

B.S. Microbiology 2003, Colorado State University
Ph.D. Biological Sciences 2008, University of Notre Dame
Postdoctoral Fellow 2008-2011, Harvard University
Mentor: Dr. Jeffrey S. Schorey
CBBI Fellow: 2007-2008
Current Position: Regional Medical Liaison, Snofi

Research Project:
Lindsay characterized the role for Mycobacterium avium surface-located glycopeptidolipids (GPLs) in modulating the host macrophage response; specifically, how they modulate cell signaling and phagosome-lysosome maturation. She found that some GPLs signal via the Toll-like receptor 2 (TLR2) and others do not. Lindsay carried out an internship in the Department of Chemistry to compare the structures of active versus non-active GPLs using GC/MS, MS/MS, and NMR analyses.

Honors:
1st Place Presentation CBBI Retreat, 2008

Publications:

  • Krzywinska, E.; Bhatnagar, S.; Sweet, L.; Chatterjee, D.; Schorey, J. S. Mycobacterium avium 104 deleted of the methyltransferase D gene by allelic replacement lacks serotype-specific glycopeptidolipids and shows attenuated virulence in mice. Mol Microbiol 2005, 56, 1262-1273.
  • Sweet, L.; Schorey, J. S. Glycopeptidolipids from Mycobacterium avium promote macrophage activation in a TLR2- and MyD88-dependent manner. J. Leukocyte Biol. 2006, 80, 415-423.
  • Schorey, J. S.; Sweet, L. The_ mycobacterial glycopeptidolipids: structure, function and their role in pathogenesis. Glycobiology 2008, 18, 832-841.
  • Sweet, L.; Zhang, W.; Torres-Fewell, H.; Serianni, A.; Boggess, W.; Schorey, J. S. Mycobacterium avium glycopeptidolipids require specific acetylation and methylation patterns for signaling through toll-like receptor 2. J Biol Chem 2008, 283, 33221-33231.
  • Sweet, L.; Singh, P.; Azad, A.; Schlesinger, L.; Schorey, J. S. Mannose receptor-dependent delay in phagosome maturation by Mycobacterium avium glycopeptidolipids. Infect. Immun. 2010, 78, 518-526.

Adriel Villegas-Estrada

Estrada

B.A. Chemistry 2004, Vassar College, Poughkeepsie, NY
Discipline: Biochemistry
Mentor: Dr. Shahriar Mobashery
CBBI Fellow: 2007-2008
Current Position: Research Administration, Dalio ICI, Weill Cornell Medical College

Research Project:
Adriel studied the mechanism of resistance of aminoglycoside-modifying enzymes, the signal transduction pathway for antibiotic resistance in Staphylococcus aureus, and the pharmacokinetic lead optimization of gelatinase inhibitors that can be used as potential drugs. He used a combination of molecular biology, NMR, X-ray crystallography, enzymology, and protein-peptide interactions to elucidate the steps required for S. aureus to generate two enzymes, β-lactamase and PBP2a.

Publications:

  • Kim, C.; Villegas-Estrada, A.; Hesek, D.; Mobashery, S. Mechanistic characterization of the bifunctional aminoglycoside-modifying enzyme AAC-Ib/AAC-Ib’ from Pseudomonas aeruginosa Biochemistry, 2007, 46, 5270-5282.
  • Lee, M.; Villegas-Estrada, A.; Celenza, G.; Boggess, B.; Toth, M.; Kreitinger, G.; Forbes, C.; Fridman, R.; Mobashery, S.; Chang, M. Metabolism of a highly selective gelatinase inhibitor generates active metabolite. Chem Biol Drug Design 2007, 70, 371-382.
  • Celenza, G.; Villegas-Estrada, A.; Lee, M.; Boggess, B.; Forbes, C.; Wolter, W. R.; Suckow, M. A.; Mobashery, S.; Chang, M. Metabolism of (4-phenoxyphenylsulfonyl)-methylthiirane, a selective gelatinase inhibitor, Chem Biol Drug Design 2008, 71, 187-196.
  • Villegas-Estrada, A.; Lee, M.; Hesek, D.; Vakulenko, S. B.; Mobashery, S. Co-opting the cell wall in fighting methicillin-resistant Staphylococcus aureus: Potent inhibition of PBP 2a by two anti-MRSA β-lactam antibiotics, J Am Chem Soc 2008, 130, 9212-9213.
  • Moraski, G. C.; Chang, M.; Villegas-Estrada, A.; Franzblau, S. G.; Mollman, U.; Miller, M. J. Structure-activity relationship of new anti-tuberculosis agents derivaed from oxazoline and oxazole benzyl esters. Eur. J. Med. Chem. 2010, 45, 1703-1716.

Mark Wacker

wacker

B.A. Biology 2000, Luther College
Ph.D. Biology 2011, University of Notre Dame
Discipline: Biology
Mentor: Dr. Michael T. Ferdig
CBBI Fellow: 2009-2011
Current Position: Postdoctoral Fellow, University of Iowa

Research Project:
Mark’s project involved the identification of compounds that map to the pfcrt locus and compounds linked to additional hotspots throughout the genome of the malaria parasite Plasmodium. He assayed global metabolite levels in the parents and progeny clones of a genetic cross between drug sensitive and drug resistant parasite clones. Metabolite extracts were analyzed by HPLC and mass spectrometry. The mass peaks, indicating inherited levels of different metabolites, are treated as phenotypes for quantitative trait loci (QTL) mapping. Mark mapped more than 500 mass peaks to a specific region in the genome. He conducted a research internship with Prof. Manuel Llinas in the Department of Molecular Biology and Prof. Joshua Rabinowitz in the Department of Chemistry, Princeton University in metabolomics to identify the compounds and conduct flux experiments.

Honors:

  • Navari Fellowship, University of Notre Dame, 2007
  • Young Investigator Award, American Society of Tropical Medicine and Hygiene, 2009

Publications:

  • Reilly, H.B.; Wacker, M.; Siwo, G.; Ferdig, M. T. Quantitative trait loci analysis in Plasmodium falciparum reveals candidate pathways regulating divergent cell cycles, BMC Genomics 2010, 11, 577. PMCID: PMC3091725
  • Wacker, M. A.; Turnbull, L. B.; Walker, L. A.; Mount, M. C.; Ferdig, M. T. Quantification of multiple infections of Plasmodium falciparum in vitro. Malar J. 2012 May 30;11:180. PMCID: PMC3483182
  • Lewis, I. A.; Wacker, M. A.; Olszewski, K. L.; Cobbold, S. A.; Baska, K. S.; Tan, A.; Ferdig, M. T.; Llinas, M., Metabolic QTL analysis chloroquine resistance in Plasmodium falciparum to impaired hemoglobin catabolism. PLoS Genet. 2014 Jan; 10(1):e1004085. PMCID: PMC3879234

Katherine Ward

ward

B.S. 2009, University of Central Arkansas, Conway, AR
Discipline: Biochemistry
Mentor: Robert Stahelin

Research Project:
Katherine’s research is focused on the characterization and prediction of novel proteins that bind to the lipid Ceramide-1-Phosphate (C1P) using biochemistry and molecular biology. Currently, Katherine is characterizing the molecular binding of C1P within cytosolic phospholipase A2 α (cPLA2α), a target that has been implicated in cerebral ischemia and atherosclerosis, in the laboratory of Prof. Olaf Wiest using computational chemistry. In this internship, Katherine will learn and incorporate molecular dynamics into her current and future research. Through these studies, the goal is to identify new proteins that bind to C1P and also aid in the development of a cPLA2α inhibitor as a potential treatment of heart attack and stroke.

Honors:

  • Selected for Oral Research Presentation at the International Experimental Biology ASBMB Conference, 2012.
  • Awarded a 2 year American Heart Association Predoctoral Fellowship 2011-2013.
  • Roger K. Bretthauer Teaching Award in Biochemistry, 2011.
  • Best Poster in Lipid Membrane Metabolism at the International Experimental Biology ASBMB Conference, 2011.
  • Kaneb Teaching Award for teaching General Chemistry Laboratory, 2011.
    *Graduated from University of Central Arkansas summa sum laude in Chemistry, 2009.

Publications:

  • Lamour NF, Wijesinghe DS, Mietla JA, Ward KE, Stahelin RV, Chalfant CE. Ceramide kinase regulates the production of tumor necrosis factor α (TNFα) via inhibition of TNFα-converting enzyme. J Biol Chem. 2011, 286, 42808-17.

Kyle Watson

kyle_watson_1

_B.A. in Chemistry, 2010, Manchester University, North Manchester, IN _
Discipline: Organic Chemistry
Mentor: Marvin J. Miller

Research Project:
Kyle is working on developing new metal-mediated methodologies for the syntheses of monocyclic and bicyclic oxamazins – heteroatom-activated b-lactam antibiotics. Kyle has been successful in using ruthenium based catalysts to synthesize the bicyclic oxamazin core and is currently working on incorporating this methodology to synthesize fully functionalized antibiotic targets. During the spring of 2014, Kyle completed an internship at Remepx Pharmaceuticals, part of the Medicines Company, in San Diego, CA. There, he was able to learn the techniques required for testing his compounds for both antibiotic activity and as enzyme inhibitors.

Internship
February – April 2014 Vice President for Biology, Rempex Pharmaceuticals, San Diego, CA. Mentor: Olga Lomovskaya.

The goal of Kyle’s internship project was to learn to do microbiological assays and biochemical assays.

Publications:

  • Watson KD, Carosso S, Miller MJ, New and Concise Syntheses of the Bicyclic Oxamazin Core Using an Intramolecular Nitroso Diels-Alder Reaction and Ring-Closing Olefin Metathesis. Org Lett. 2013, 15, 358.

Tim Wencewicz

wencewicz

B.S. Chemistry and Applied Mathematics 2006, Southeast Missouri State University, Cape Girardeau, MO
Ph.D. Chemistry 2011, University of Notre Dame
Discipline: Organic Chemistry
Mentor: Dr. Marvin J Miller
CBBI Fellow: 2007-2010
Current Position: Assistant Professor, Washington University, St. Louis

Research Project:
Tim’s project involved the synthesis and study of biologically active siderophore-drug conjugates as potential targets for “Trojan Horse” drug delivery in bacteria. He used synthetic organic chemistry, microbiology, and biochemistry. The goals were to evaluate the impact of the siderophore delivery system on the spectrum and potency of antibiotic activity and probing the mechanism of action of the conjugates using kinetic drug release studies and fluorescent probes. Tim completed an internship with Dr. Ute Möllmann at the Hans Knoll Institute in Germany to learn microbial growth promotion and inhibition assays that allowed him to test the biological activity of the siderophore-drug conjugates that he synthesized. Since his return from his internship, Tim set up a fully operational antibiotic testing facility in the Miller lab capable of performing growth inhibition assays (agar diffusion and MIC determination) and growth promotion assays (agar diffusion) using bacteria and fungi.

Honors:

  • Brother Columba Curran Fellowship, 2006
  • Kaneb Outstanding Teaching Assistant, 2007
  • First Place Presentation, CBBI Symposium, 2010
  • Jeremiah P. Freeman Award for Teaching in Organic Chemistry, 2010
  • Bayer Predoctoral Research Fellowship, 2010
  • Grace Fellowship, 2010
  • ACS Div. Org. Chem. Graduate Research Symposium Awardee, 2010
  • NIH National Graduate Student Research Festival Awardee, 2010

Publications

  • Wencewicz, T. A.; Long, T. E.; Möllmann, U.; Miller, M. J. Is Drug Release Necessary for Antimicrobial Activity of Siderophore-drug Conjugates? Synthesis and Biological studies of the Naturally Occurring Salmcin “Trojan Horse” Antibiotics and Synthetic Desferridanoxamine-antibiotic Conjugates, Biometals 2009, 22, 633-648.
  • Mayfield, J. A.; Frederick, R. E.; Streit, B. R.; Wencewicz, T. A.; Ballou, D. P.; DuBois, J. L. Comprehensive Spectroscopic, Steady State, and Transient Kinetic Studies of a Representative Siderophore-Associated Flavin Monooxygenase. J. Biol. Chem. 2010, 285, 30375-88.
  • Yan, S.; Miller, M. J.; Wencewicz, T. A.; Möllmann, U. Syntheses and Biological Evaluation of New Cephalosporin-oxazolidinone Conjugates.” Med. Chem. Comm. 2010, 1, 145-148.
  • Yan, S.; Miller, M. J.; Wencewicz, T. A.; Möllmann, U. Syntheses and Antibacterial Activity Studies of New Oxazolidinones from Nitroso Diels-Alder Chemistry. Bioorg. Med. Chem. Lett. 2010, 20, 1302-1305.
  • Wencewicz TA, Yang B, Rudloff JR, Oliver AG, Miller MJ. N-O chemistry for antibiotics: discovery of N-alkyl-N-(pyridin-2-yl)hydroxylamine scaffolds as selective antibacterial agents using nitroso Diels-Alder and ene chemistry. J Med Chem. 2011, 54, 6843-58.
  • Wencewicz, T. A.; Oliver, A. G.; Miller, M. J.;, Iron(III)-templated macrolactonization of trihydroxamate siderophores. Org Lett. 2012 Sep 7;14(17):4390-4393. PMCID: PMC3436969
  • Wencewicz, T. A.; Long, T. E.; Möllmann, U.; Miller, M. J., Trihydroxamate siderophore-fluoroquinolone conjugates are selective sideromycin antibiotics that target Staphylococcus aureus. Bioconjug Chem. 2013 Mar 20;24(3):473-486. PMCID: PMC3633530
  • Wencewicz, T. A.; Miller, M. J., Biscatecholate-monohydroxamate mixed ligand siderophore-carbacephalosporin conjugates are selective sideromycin antibiotics that target acinetobacter baumannii. J Med Chem. 2013 May 23;56(10):4044-4052. PMCID: PMC3690592