[PDF] graduate studies in chemistry and biochemistry

30004_7chem_gradrecruitment_9_29_17_compressed.pdf ἞ᴜᬝᨙ ᠚ᬜ᜙ᠠ᜖    Me Me OMeMe Me O OHO Me Me OO H O OH Me O OOMe O O OOHO Me Me O MeMe O H HOH OH Me Me Message from the Chair ..................................................2 The University of Notre Dame .......................................3 The Department of Chemistry and Biochemistry ...........4 Research Facilities ..........................................................4 ............................................5 The Graduate Program ....................................................6 Financial Support ............................................................6 Application Process ........................................................8

Housing

...........................................................................8 Faculty Research Interests .......................................12-58Brandon Ashfeld

Brian M. Baker

Brian Blagg

Paul Bohn

Jessica Brown

Seth N. Brown

Merlin Bruening

Jon Camden

Ian Carmichael

Francis J. Castellino

Patricia L. Clark

Steven Corcelli

Norman Dovichi

Haifeng Gao

J. Daniel Gezelter

Holly Goodson

Gregory V. Hartland

Paul Helquist

Paul W. Huber

Amanda B. Hummon

Vlad M. Iluc

Prashant Kamat

S. Alex Kandel

Masaru K. Kuno

A. Graham Lappin

Marya Lieberman

Laurie Littlepage

Shahriar Mobashery

John Parkhill

Jerey W. Peng

Zachary Schultz

Anthony S. Serianni

Arnaldo Serrano

Slavi C. Sevov

Bradley D. Smith

Sharon Stack

Rich Taylor

Emily Tsui

Matt Webber

Olaf WiestEnergy

Life Processes

Materials

Measurement

Medicine

Sythesis

Theory

Research Specialties

Tenured and Tenure-

Track Faculty

Concurrent Faculty

Dave Bartels

Baar Bilgiçer

Peter C. Burns

William Schneider

Matthew Weber

Research Faculty

Adjunct Faculty

Mayland Chang

Victoria Ploplis

Sergei Vakulenko

Karen Cowden Dahl

Margaret Schwarz

1

NOTRE DAME

FROM THE CHAIR

Şank you for your interest in the Department of Chemistry and Biochemistry at the University of Notre Dame! Şis brochure provides an overview of the department and the research of our faculty. We have major strengths in all areas of modern chemistry and biochemistry and are deeply involved in interdisciplinary research. We have specialized concentrations in nanotechnology, materials chemistry, supramolecular chemistry, computational chemistry, analytical chemistry, and molecular biophysics. Şe presence of chemistry and biochemistry in one department is a signicant advantage, and provides for state of the art research in chemical biology, the detection of disease, the discovery of new drugs, and the development of new molecular-based therapies. Because of the interdisciplinary nature of our research, our faculty collaborate closely with other researchers across the university, such as those in the departments of biological sciences, physics, and chemical and biomolecular engineering. Şese eorts are supported by collaborative centers on campus with research missions that depend critically on the chemical and biochemical sciences. We strive to provide our research and training programs with the best facilities and take pride in our modern research laboratories, state of the art instrumentation, and outstanding support personnel. Graduate students are fundamental to all of the department"s research endeavors. Aer graduation, future success is typically found in academia, research institutions, and private industry. At the University of Notre Dame, our chemistry and biochemistry graduates are an investment in the future. We would be thrilled to have you join us.

Sincerely,

Brian M. Baker

Rev. John A. Zahm Professor and Chair, Department of Chemistry and

Biochemistry

23

CHEMISTRY AND

BIOCHEMISTRY

T he graduate program in chemistry and biochemistry at Notre Dame has experienced a period of sustained growth over the last decade through the support of the University and the endeavors of our internationally recognized faculty. On a yearly basis, the department regularly supports approximately 180 graduate students and 50 postdoctoral fellows and receives external research funding in excess of $9 million. This places the department consistently within the top 20 federally funded research programs in the country.

Our research laboratories are primarily in two

adjoining buildings, Nieuwland Science Hall and the Stepan Hall of Chemistry and Biochemistry. In the summer of 2016 several of our investigators moved to the newly completed McCourtney Hall, a multidisciplinary research building housing

100,000 square feet of laboratory space and an

abundance of collaborative and team spaces.

Along with the Jordan Hall of Science, one of

the premier instructional science buildings in the country, the research and teaching facilities available to the department have nearly tripled over the past 10 years.

FACILITIES

Genomics & Bioinformatics Core Facility

can accommodate a range of sequencing and expression analyses. ?e facility operates three microarray platforms for analysis of transcripts from various tissue types and gDNA genotyping and comparative genome hybridiza- tion. genomics.nd.edu

Magnetic Resonance Research Center

houses the following array of FT-NMR spectrometers: an 800

MHz, a 700 MHz, a 600 MHz, three 500 MHz, two

400 MHz, and a 300 MHz (solid-state). All of the spec-

trometers are multinuclear and a large variety of probes are available. nmr.nd.edu

Mass Spectrometry and Proteomics

Facility provides instrumentation and expertise for the analyses of compounds ranging from small organic mole- cules to large biomolecules with applications in the areas of metabolomics, proteomics, and lipidomics. massspec.nd.edu

Materials Characterization Facility

o?ers a diverse range of instrumentation, including FTIR and UV-Vis-NIR spectrometers, Raman microscopy, X-ray photoelectron spectrometry, and di?erential scanning calorimetry. mcf.nd.edu

Molecular Structure Facility

houses three state-of- the-art X-ray di?ractometers, which are used for routine low-temperature analysis of single crystal and powder samples. ?e facility is open to all of our graduate stu- dents who have the opportunity to perform all aspects of their crystallography experiments. xray.nd.edu

Notre Dame Integrated Imaging Facility

is a state-of-the-art research core that provides an integrated suite of sophisticated microscopes and imaging stations that enable researchers to attack the most complex, mod- ern research problems. Microscopic and biological imag- ing are among the most common experimental techniques employed by science and engineering researchers at the

University of Notre Dame.

ndiif.nd.edu

Chemical Synthesis and Drug Discovery

(CSDD) Facility supports translational biomedical re- search by providing expertise in the preparation of small molecules for use in hit veri?cation, lead development, and as biological probes. ?e CSDD also oversees the

Notre Dame Chemical Compound Collection, which

contains more than 20,000 unique chemical entities. drugdiscovery.nd.edu

AFFILIATED

RESEARCH CENTERS

N ot only does the department make use of its own excellent research facilities, it also enjoys collaborative research opportunities with departments across engineering and science disciplines in a number of aliated research centers.

W. M. Keck Center for Transgene Research

e Keck Center was established in 1995 and utilizes more than 50 difierent strains of mice, top interdisci- plinary expertise, and the most advanced equipment to address an area of investigation that is at the forefront of medical research: hemostasis. transgene.nd.edu

Radiation Laboratory

e Notre Dame Radiation Laboratory, a joint venture of the University of Notre Dame and the U.S. Depart- ment of Energy, is an international center advancing the understanding of the interaction of radiation (both light and ionizing) with matter. rad.nd.edu

Center for Sustainable Energy

at Notre Dame (ND Energy) ND Energy brings together researchers to address the global challenges of a more sustainable energy future, emphasizing approaches to transformative solar, clean- er fossil, and safer nuclear power. energy.nd.edu

Center for Environmental Science

and Technology (CEST) CEST is a cooperative efiort between Notre Dame"s colleges of science and engineering, fostering inter- disciplinary environmental research and education by providing cutting-edge analytical technologies needed to address complex environmental problems.

cest.nd.eduHarper Cancer Research InstituteResearchers in the Harper Cancer Research Institute are exploring the genetic basis of colon, prostate, breast, and ovarian cancers with unique animal models de-

veloped in the research center. Results of these studies may provide the basis for understanding the origin of these diseases as well as provide molecular targets for the development of new drugs and other treatments. harpercancer.nd.edu

Center for Nano Science and Technology

Researchers in this center explore new device concepts and associated architectures enabled by novel phenom- ena on the nanometer scale. e center catalyzes multi- disciplinary research and education in nanoelectronics, molecular electronics, nano-bio and bio-uidic micro- structures, circuits, and architectures. nano.nd.edu

Advanced Diagnostics & Therapeutics

is center is a community of aliated researchers who tackle a wide range of biomedical and environmen- tal health problems - such as sepsis, cancer, inuenza, wound healing, drug addiction, mosquito-borne diseas- es, autism, cystic brosis, air pollution, invasive species, and many others - through innovation, invention, and real-world applications. advanceddiagnostics.nd.edu

Center for Research Computing

is University resource provides state-of-the-art, high- end computing, communications infrastructure, and software as well as skilled technical computing stafi. crc.nd.edu

Warren Family Research Center for Drug

Discovery and Development

e Warren Center is a resource for a highly productive and renowned group of drug discovery faculty with expertise and interest in areas such as neurological and central nervous system disorders, infectious disease, cancer, and rare diseases. drugdiscovery.nd.edu

McCourtney Hall

45

As you work toward your degree ...



FINANCIAL SUPPORT

   )

THE GRADUATE

PROGRAM

  "  

APPLICATION PROCESS

HOUSING

  67

The recreational facilities on campus are

extensive, with an ice rink, several basketball courts, handball/racquetball courts, squash courts, and an Olympic-size pool in the

Joyce Center alone. Two golf courses; a

recreational sports center, including a -mile, suspended running track; a pavilion with six indoor tennis courts (to complement the 24 outdoor courts); and numerous other venues for sports provide for the physical activities so important to students. The department also has several different intramural sports teams.

Cultural events are important at Notre Dame.

The Snite Museum of Art is home to five

galleries and more than 17,000 items, and the magnificent DeBartolo Performing Arts Center hosts everything from movies to symphonic orchestras to international performers, all here on the Notre Dame campus.

Notre Dame fields 26 varsity athletic

teams, with the football team being the most famous, hosting more than 80,000 fans per game each fall. Every student has the opportunity to purchase tickets for all campus sporting events. 89
Me OO Me OOOMe OO OOHO Me Me HOH OH Me Me Me Me OMeO MeMe O OOH Me OO OOHO MeH OH Me

Associate Professor

Director of Graduate Studies

(574) 631-1727 bashfeld@nd.edu

Rev. John A. Zahm Professor

Department Chair

(574) 631-9810 brian-baker@nd.edu

Ruth L. Kirschstein National Institute of Health

Postdoctoral fellow, Stanford University, 2004-07

PhD, Chemistry, University of Texas at Austin, 2004

BS, Chemistry, University of Minnesota, 1998

Synthetic Organic Chemistry

Our research interests lie in the development of new methods for the synthesis of complex natural products and designed materials. Our main objective is to use new chemical constructs to design and synthesize improved chemotherapies for brain and CNS cancers and materials that will ultimately lead to the reduction of atmospheric concentrations of anthropogenic CO 2 . One area our program seeks to address is the issue of suitable brain and nervous system cancer drug treatments by evaluating diarylheptanoids bearing promising cytotoxicity and blood brain barrier (BBB) transcytosis properties. We are currently working toward the development of two new synthetic methods that will a tandem reaction sequence composed of mechanistically distinct transformations facilitated by a single catalyst to rapidly assemble all alkyl-substituted tertiary carbons centers. Our second area focuses on the formation of Csp 2 -N and Csp 2 -C bonds through the development of phosphorus-mediated C-C and C-N bond formations that ultimately circumvents the need for traditional organometallic or transition metal-based reagents. Managing the impact of human activities on the concentration of CO 2 in the atmosphere is the most far-reaching environmental challenge facing the world today. Our ultimate goal is the development of a regenerative material that will undergo selective super-stoichiometric carbon capture with near-zero parasitic energy consumption. Recognizing that C-C and C-X chemical bonds are convenient media for energy storage, transport, and consumption, our efforts rely on the design and synthesis of functionalized N-heterocyclic anions and carbenes for energy 2 .

Honors and Awards

National Science Foundation CAREER Award, 2011

University of Notre Dame Faculty Scholarship Award, 2009 Ruth L. Kirschstein National Postdoctoral Fellowship Award,

2004-2007

Selected Publications

Wilson, E.E.; Rodriguez, K.X.; Ashfeld, B.L. “Stereochemical implications in the synthesis of 3,3"-spirocyclopropyl oxindoles from beta-aryl/alkyl-substituted alkylidene oxindoles." Tetrahedron 2015, 71(53), 5765-5775. Haugen, K.C.; Rodriguez, K.X.; Chavannavar, A.P.; Oliver, A.G.; Ashfeld, B.L. “Phosphine-mediated addition of

1,2-dicarbonyls to diazenes: an umpolung approach

toward N-acyl hydrazone synthesis." Tetrahedron

Lett.2015, 56(23), 3527-3530.

Gianino, J.B.; Campos, C.A.; Lepore, A.J.; Pinkerton, D.M.; Ashfeld, B.L. “Redox and Lewis Acid Relay Catalysis: A Titanocene/Zinc Catalytic Platform in the Development of Multicomponent Coupling Reactions." J. Org. Chem.

2014, 79(24), 12083-12095.

Chavannavar, A.P.; Oliver, A.G.; Ashfeld, B.L. “An umpolung approach toward N-aryl nitrone construction: a phosphine-mediated addition of 1,2-dicarboyls to nitroso electophiles." Chem. Commun. 2014, 50 (74), 10854-

10856.

Meloche, J.L.; Vednor, P.T.; Gianino, J.B.; Oliver, A.G.; Ashfeld, B.L. “Titanocene-catalyzed metallation of propargylic acetates in homopropargyl alcohol synthesis."

Tetrahedron Lett. 2014, 55 (36), 5025-5028.

Fleury, L. M.; Wilson, E. E.; Vogt, M.; Fan, T. J.; Oliver, A. G.; Ashfeld, B. L. “An Amine-Free Approach Toward N-Toluenesulfonyl Amidine Construction: A Phosphite-

Mediated Beckmann-Like Ligation of Oximes and

Azides."Angew. Chem. Int. Ed. 2013, 52 (44), 11589-

11593.

Postdoctoral fellow, Harvard University, 1998-2001

PhD, Biochemistry, University of Iowa, 1997

BS, Biochemistry, New Mexico State University, 1992

Biophysics and Structural Biology of Molecular

Recognition and Cellular Communication

does recognition lead to cellular communication, and how do the physical aspects of these processes give rise to biological function? Baker studies these broad areas utilizing a diverse array of structural, biophysical, biochemical, and biological approaches. The work emphasizes molecular recognition, communication, and function in the general areas of cellular immunity and bacterial antibiotic resistance. Techniques used in the laboratory include solution biophysics, protein crystallography and NMR, mass spectrometry, computational biochemistry, and biological experiments with cell and animal models. Much of the work focuses on the basis for antigen recognition in cellular immunity. The goal of this research is to understand how some antigenic ligands, yet avoid others. The laboratory focuses on the T cell receptor and its ligand, small peptides bound and "presented" by major histocompatibility complex proteins, rise to recognition behavior. Beyond helping to understand the basic biochemistry of molecular recognition, these studies have implications for the functioning of the immune system, the immune response to cancer and infectious disease, and autoimmunity. Another main project in the laboratory is the physical basis for T cell signaling. The T cell receptor complex on the surface of a T cell is a large, multi-protein supramolecular assembly. The laboratory aims to understand how this assembly is able to communicate the presence of a ligand to the interior of a cell. Utilizing basic principles of allosteric communication, the contribute to architectural changes on the outside of the cell that alter the positions of signaling modules on the inside of the cell. An important goal of this project is to determine the three- dimensional structure of the T cell receptor complex on the surface of a living cell, which will directly relate structural and physical properties to biology. In partnership with computational biologists and immunologists, the laboratory is engineering immune receptors to target antigens

strengthening the immune response to cancer. In the context of this work, together with collaborators the laboratory is generating mice cancer. In a related project, the laboratory is working with medicinal chemists to design new vaccine candidates based on cellular

immunity. The laboratory also studies the evolution of bacterial antibiotic the presence of antibiotics via a "sensor" protein on the cell surface. Recognition of an antibiotic is communicated into the cell, leading to upregulation of the resistance machinery. The laboratory is studying how these sensor proteins evolved from machinery utilized in cell wall biosynthesis and how small function. Taking cues from the work in the immune system, the laboratory is asking how recognition of an antibiotic by the sensor is communicated from the outside of the cell to the inside, with the long term goal of disrupting this process for the development of novel classes of antibiotics.

Awards

Rev. Edmund P. Joyce C.S.C Award for Excellence in

Undergraduate Teaching, 2014

Director of Graduate Studies Award, 2012

Research Scholar of the American Cancer Society, 2005

NSF CAREER Award, 2005

Fellow of the Cancer Research Institute, 1998-2001

Selected Publications

Harris, D.T.; Singh, N.K.; Cai, Q.; Smith, S.N.; Vander Hooi, C.; Procko, E.; Kranz, D.M.; Baker, B.M. “An engineered switch in T cell receptor specificity leads to an unusual but functional binding geometry." Structure 2016, 24(7),

1142-1154.

Ayres, C.M.; Scott, D.R.; Corcelli, S.A.; Baker, B.M. “Differential utilization of binding loop flexibility in T cell receptor ligand selection and cross-reactivity." Sci.

Reports 2016, 6, 25070.

Riley, T.P.; Singh, N.K.; Pierce, B.G.; Weng, Z.; Baker,

B.M. “Computational modeling of TCR-pMHC

complexes."Methods Mol. Biol. 2016, 1414, 319-340. Blevins, S.J.; Pierce, B.G.; Singh, N.K.; Riley, T.P.; Wang, Y.; Spear, T.T.; Nishimura, M.I.; Weng, Z.; Baker, B.M. “How structural adaptability exists alongside HLA-A2 bias in the human ?? TCR repertoire." P. Natl. Acad. Sci. USA 2016,

113(9), E1276-E1285.

chemistry .nd.educhemistry.nd.edu 1213
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Concurrent Professor

(574) 631-5561 bartels.5@nd.edu ὁÇ

Concurrent Associate Professor

(574) 631-1429 bbilgicer@nd.edu

Postdoctoral fellow, Brown University, 1982-85

PhD, Chemistry, Northwestern University, 1982

BS, Chemistry, Hope College, 1977

Radiation Chemistry and Photochemistry

of Water Ionizing radiation plays a major role in many modern chemical technologies involving polymerization and sterilization. It plays a decisive role in nuclear power plants and interstellar chemistry. The initial ionization event separates charges and spin, forming ions and free radicals whose subsequent reactions dominate the chemistry. The Bartels group uses multiple experimental and theoretical tools to quantify and understand the free radical reactions. These include electron pulse radiolysis with transient optical, conductivity, and electron paramagnetic resonance detection, and molecular dynamics simulations. Recent work has focused on the free radical reactions in nuclear reactor cooling loops around 300°C to develop a comprehensive and accurate model of the chemistry. Hydrated electrons, hydrogen atoms, and OH radicals are formed as the dominant initial species, and each of these are very interesting from the point of view of fundamental physical chemistry. A major goal is understanding and modeling reactions of solvated electrons. Generation IV reactors are supposed to use supercritical water coolant up to 500°C, and the density-dependence of reaction rates in the near-critical region becomes of great practical importance. New work involves reactions of metal ion and metal oxide corrosion products, and direct microscopy measurements of radiation-enhanced corrosion. chemistry .nd.educhemistry.nd.edu Postdoctoral fellow, Harvard University, 2005-2008

PhD, Chemistry, Tufts University, 2004

BS, Chemistry, Bogazici University, Turkey, 1998

Biophysical Chemistry and Biomolecular

Drug Design

Multivalent binding is the simultaneous interaction of multiple ligands present on one biological entity with multiple receptors on another. Multivalent interactions carry great importance in biology and are observed from viral infection to immune system surveillance of pathogens and cancer cells. Our group is interested in multivalency from two angles: 1) developing an improved understanding for the thermodynamics and kinetics of multivalent interactions; and 2) designing multivalentagents for diagnostic and therapeutic applications in cancers, autoimmune diseases, allergies, and HIV. We believe that a deeper understanding of the thermodynamics and kinetics of multivalent interactions in biological systems is imperative in the development of new diagnostic and therapeutic agents. ?e research projects in our group are developed around the common theme of developing multivalent molecules for not just enhancing binding a?nity, but also for providing selectivity in binding. An example project for incorporation of multivalency in therapeutic molecular design application is reduction of non-speci?c toxicity associated with pharmaceutical antibodies by delivering them as bicyclic complexes. Currently, there are more than 30 pharmaceutical antibodies used worldwide in the treatment of a wide range of diseases including viral infection, cancer, and autoimmune diseases. ?erapeutic antibodies rely on the high a?nity interactions with a cell surface receptor that is overexpressed on cancer cells and has a lower expression pro?le or is supposedly non-existent on healthy cells. Non-speci?c toxicity, however, still remains a problem with therapeutic antibodies. We are currently developing a targeting strategy where we increase the selectivity of therapeutic antibodies for their target cells by delivering them as bicyclic complexes formed via interactions with corresponding synthetic trivalent ligands (Figure 1). ?e bicyclic complexes have a relatively low dissociation constant, which keeps the antibody molecules in the form of the complex. ?erefore, only target cells with a high receptor density (as in the case of cancer cells) would be able to competitively dissociate the bicyclic complexes and recruit the antibodies to their surfaces, thereby providing improved selectivity for the therapeutic agent. We are currently collaborating with the pharmaceutical industry to develop a reduced-toxicity

drug-delivery-system for an FDA approved antibody therapeutic.?e ultimate goal of our research program is to provide innovative

therapeutic and diagnostic tools to improve patient outcomes.

Selected Publications

Deak, P.E.; Vrabel, M.R.; Pizzuti, V.J.; Kiziltepe, T.; Bilgicer, B. “Nanoallergens: A multivalent platform for studying and evaluating potency of allergen epitopes in cellular degranulation." Exp. Biol. Med. 2016, 241(9), 996-1006. Mustafaoglu, N.; Alves, N.J.; Bilgicer, B. “Oriented

Immobilization of Fab Fragments by Site-Specific

Biotinylation at the Conserved Nucleotide Binding Site for Enhanced Antigen Detection." Langmuir 2015, 31(35),

9728-9736.

Stefanick, J.F.; Kiziltepe, T.; Bilgicer, B. “Improved Peptide- Targeted Liposome Design Through Optimized Peptide Hydrophilicity, Ethylene Glycol Linker Length, and Peptide Density." J. Biomed. Nanotechnol. 2015, 11(8), 1418- 1430.
Mustafaoglu, N.; Alves, N.J.; Bilgicer, B. “Site-specific fab fragment biotinylation at the conserved nucleotide binding site for enhanced ebola detection." Biotechnol. Bioeng.

2015, 112(7), 1327-1334.

Ashley, J.D.; Stefanick, J.F.; Schroeder, V.A.; Suckow, M.A.; Alves, N.J.; Suzuki, R.; Kikuchi, S.; Hideshima, T.; Anderson, K.C.; Kiziltepe, T.; Bilgicer, B. “Liposomal carfilzomib nanoparticles effectively target multiple myeloma cells and demonstrate enhanced efficacy in vivo."

J. Control. Release 2014, 196, 113-121.

Handlogten, M.W.; Deak, P.E.; Bilgicer, B. “Two-Allergen

Model Reveals Complex Relationship between IgE

Crosslinking and Degranulation." Chem. Biol. 2014,

21(11), 1445-1451.

Selected Publications

Kumar, A.; Walker, J. A.; Bartels, D. M.; Sevilla, M. D. A Simple ab Initio Model for the Hydrated Electron That Matches Experiment. The Journal of Physical Chemistry A

2015, 119, 9148-9159.

Kanjana, K.; Courtin, B.; MacConnell, A.; Bartels, D. M. Reactions of Hexa-aquo Transition Metal Ions with the Hydrated Electron up to 300 degrees C. J. Phys. Chem. A

2015, 119, 11094-11104.

Nuzhdin, K.; Bartels, D. M. Hyperfine coupling of the hydrogen atom in high temperature water. J. Chem. Phys.

2013, 138, 8.

Wu, W. Q.; Nuzhdin, K.; Vyushkova, M.; Janik, I.; Bartels, D. Comparison of Acid Generation in EUV Lithography Films of Poly(4-hydroxystyrene) (PHS) and Noria Adamantyl Ester (Noria-AD50). J. Phys. Chem. B 2012, 116, 6215- 6224.
Hare, P. M.; Price, E. A.; Stanisky, C. M.; Janik, I.; Bartels, D. M. Solvated Electron Extinction Coefficient and Oscillator Strength in High Temperature Water. J. Phys. Chem. A

2010, 114, 1766-1775.

1415
Me OO Me OOOMe OO OOHO Me Me HOH OH Me Me Me Me OMeO MeMe O OOH Me OO OOHO MeH OH Me

Arthur J. Schmitt Professor

Director, Advanced Diagnostics &

Therapeutics

(574) 631-1849 pbohn@nd.edu chemistry .nd.educhemistry.nd.edu

Charles Huisking Professor Director,

Warren Family Research Center for

Drug Discovery and Development

(574) 631-6877 bblagg@nd.edu

PhD, Chemistry, University of Wisconsin, 1981

BS, Chemistry, University of Notre Dame, 1977

Molecular Nanoelectronics

Our group is interested in the active control of interfacial chemistry and morphology, as an entrée to developing nanoscale chemical devices for sensing, separations, and signal processing. Currently these interests are being explored in four main research thrusts in our group: (1) chemical sensors; (2) single molecule chemical imaging.

Chemical Sensors.

We study both conductance-based and

plasmonic chemical sensors. The conductance sensors are based on adsorbate-induced surface wave-packet scattering as monitored in wires that, at their narrowest point, are only a single atom wide. This nanosensor is sensitive down to the detection of single molecules, and the sensing structure can be regenerated for multiple readout cycles. Plasmonic sensing takes advantage of second- generation plasmonic techniques employing either extraordinary optical transmission in sub-wavelength aperture arrays or phase- shift imaging to study problems in bioanalysis, such as strain-

Single Molecule Spectroelectrochemistry.

We utilize specialized

nanophotonic structures, such as zero-mode waveguides, in order to isolate and study the behavior of single enzyme molecules. Currently, we are investigating FAD-bearing oxidases in which cycling through redox states results in a characteristic on-off emission pattern that allows us to watch single enzyme turnover events. We are working to couple these observations to Faradaic electron transfer events, thereby enabling the observation of single electron transfer events. transistors. Incorporating molecular recognition elements into and opens the way to studies of controlled release and single- selectively control transport over nanometer distances.

Chemical Imaging.

Our chemical imaging projects focus on

Raman images acquired in our laboratory with SIMS and LDI mass spectrometric images acquired by our collaborators. Putting together information from two complementary spectroscopic imaging probes allows us to obtain much more detailed information than would be available from either technique alone. At present, these approaches are being applied to problems in

microbial communication and cancer biology.

Awards

Fellow, Society for Applied Spectroscopy, 2012

Haines-Morris Lecturer, University of Tennessee, 2011

Kritzler Lecturer, Ohio Northern University, 2011

Theophilus Redwood Award, Royal Society of Chemistry, 2010

Fellow, Royal Society of Chemistry, 2008

Selected Publications

Ma, C.; Xu, W.; Wichert, W.R.A.; Bohn, P.W. “Ion Accumulation and Migration Effects on Redox Cycling in Nanopore Electrode Arrays at Low Ionic Strength," ACS Nano 2016,

10, 3658-3664. [DOI 10.1021/acsnano.6b00049].

Zaino, L.P. III; Grismer, D.A.; Han, D.; Crouch, G.M.; Bohn, P.W. “Single Molecule Spectroelectrochemistry of Freely Diffusing Flavin Mononucleotide in Zero-Dimensional Nanophotonic Structures," Faraday Disc. 2015, 184,

101-115. [DOI 10.1039/C5FD00072F]

Ma, C.; Zaino, L.P. III; Bohn, P.W. “Self-Induced Redox Cycling Coupled Luminescence on Nanopore Recessed Disk-Multiscale Bipolar Electrodes," Chem. Sci. 2015, 6,

3173-3179. [DOI 10.1039/c5sc00433k]

Hwang, T.-W.; Bohn, P.W. “Potential-Dependent Restructuring and Chemical Noise at Au-Ag-Au Atomic Scale Junctions,"

ACS Nano, 2014, 8, 1718-1727. [DOI 10.1021/

nn06098u] NIH Postdoctoral Fellow, The Scripps Research Institute,

1999-2002

Ph.D. in Organic Chemistry, University of Utah, 1999 B.A. in Chemistry and Environmental Studies, Sonoma

State University, 1994

Organic Chemistry, Medicine, and Synthesis

The 90 kDa heat shock proteins (Hsp90) are molecular chaperones that are required for the refolding of denatured proteins and the maturation of nascent polypeptides into their biologically active, three-dimensional structures. In fact, numerous proteins represented in all ten hallmarks of cancer are dependent upon Hsp90 for conformational maturation. Hsp90 inhibition provides a combinatorial attack on multiple pathways responsible for malignant cell growth and proliferation. Consequently, Hsp90 has emerged as a promising target for the development of cancer chemotherapeutics. Hsp90 contains two ATP binding sites, and in order to fold nascent polypeptides into biologically active proteins, Hsp90 catalyzes the hydrolysis of ATP. ATP hydrolysis provides the Hsp90 protein folding machinery the requisite energy for folding "client" proteins into their correct three-dimensional conformation. Disruption of this folding process results in the destabilization of Hsp90 "client" protein complexes, which leads to ubiquitinylation and proteasome-mediated degradation of the protein substrate. The N-terminal ATP binding site is inhibited by the natural products geldanamycin (GDA) and radicicol (RDC). Numerous (~20) analogs of these natural products as well as the nucleotide itself have undergone clinical evaluation for the potential treatment of cancer. Unfortunately, the vast majority of these molecules have failed. The current hypothesis is that on-target toxicities are produced when all four Hsp90 isoforms are targeted simultaneously. Therefore, we are working towards ơ manifest biological activities that are likely to be useful for the treatment of disease. our collaborators, Len Neckers (National Cancer Institute), who demonstrated that the coumarin antibiotics, including novobiocin, inhibit the C-terminal ATP binding site and lead to

the degradation of Hsp90 client proteins similarly to N-terminal for further clinical evaluation and thus represents an opportunity the most potent C-terminal inhibitors of Hsp90 yet discovered and have demonstrated the Hsp90 inhibitors possess potent neuroprotective activities against Alzheimer's, Parkinson's, diabetic peripheral neuropathy, and Multiple Sclerosis. Through optimization of the scaffold, we have produced a neuroprotective agent that is currently in Phase I human clinical trials for neuropathy.

The major goals for members of the Blagg Research Team are to design, synthesize, and evaluate novel inhibitors of the Hsp90 protein folding process. To achieve these goals, we use computer modeling to design new molecules that bind these ATP-binding sites, we develop new organic reactions that allow access to the develop assays that are suitable for determining the biological effects of our rationally designed Hsp90 inhibitors. We are currently engaged in more than 50 collaborative studies with researchers throughout the world.

Awards

Baxendale Innovation Award, University of Kansas, 2015

Leading Light Award, University of Kansas, 2013

American Chemical Society David W. Robertson Award in

Medicinal Chemistry, 2009

American Cancer Society Research Scholar Award, 2006

Selected Publications

Davis, R.E.; Zhang, Z.; Blagg, B.S.J. “A scaffold merging approach to Hsp90 C-terminal inhibition: synthesis and evaluation of a chimeric library" MedChemComm

2017, 8(3), 593-598.

Garg, G.; Zhao, H.P.; Blagg, B.S.J. “Design, synthesis and biological evaluation of alkylamino biphenylamides as Hsp90 C-terminal inhibitors" Bioorg. Med. Chem.

2017, 25(2), 451-457.

Mishra, S.J.; Ghosh, S.; Stothert, A.R.; Dickey, C.A.; Blagg, B.S.J. “Transformation of the Non-Selective

Aminocyclohexanol-Based Hsp90 Inhibitor into a

Grp94-Selective Scaffold" ACS Chem. Biol. 2017,

12(1), 244-253.

Ghosh, S.; Liu, Y.; Garg, G.; Anyika, M.; McPherson, N.T.; Ma, J.C.; Dobrowsky, R.T.; Blagg, B.S.J. “Diverging Novobiocin Anti-Cancer Activity from Neuroprotective Activity through Modification of the Amide Tail" ACS

Med. Chem. Lett. 2016, 7(8), 813-818.

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Assistant Professor

(574) 631-6486 jbrown33@nd.edu chemistry .nd.educhemistry.nd.edu American Cancer Society Postdoctoral Fellow, Yale

University, 2012-2014

PhD, Biochemistry, The Ohio State University, 2010 BS, Chemistry and Biological Sciences, Wright State

University, 2005

Structural, Biochemical & Cellular Roles of RNA

Triple Helices

RNA structure is largely viewed as being single-stranded or double-stranded, although triple-stranded RNA structures were deduced to form in test tubes almost 60 years ago. Despite this early discovery, only four examples of RNA triple helices have been validated in eukaryotic cellular RNAs. ?e long-term goal of the Brown laboratory is to understand the structural, biochemical, and cellular roles of RNA triple helices using the MALAT1 triple helix as a model. ?is triple helix forms at the 3¢ end of the long noncoding RNA, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1). ?is triple helix forms when a U-rich internal loop of a stem-loop structure binds and sequesters a downstream 3"-terminal A-rich tract. ?is unique triple- helical structure, composed of nine U•A-U triples separated by a C+•G-C triple and C-G doublet, protects MALAT1 from an uncharacterized rapid nuclear RNA pathway. ?e fundamental structural and biochemical properties of RNA triple helices remain to be rigorously characterized. ?e Brown laboratory is interested in several key questions. Do proteins bind speci?cally to the MALAT1 triple helix? Is there an undiscovered class of triple-stranded RNA binding proteins? How does the cell degrade a highly stable triple-helical RNA structure? What is the relative stability of canonical (U•A-U and C•G-C) versus non- canonical base triples? Can successive non-canonical base triples form a stable triple helix? What are the structural parameters of an ideal RNA triple helix? What is the folding pathway of an RNA triple helix? What other RNA triple helices exist in mammalian cells? To investigate these questions, we are currently using a variety of approaches, including X-ray crystallography, cell-based assays, molecular biology, classical biochemistry, and high- throughout methods. Studying the MALAT1 triple helix will advance our understanding of cancer. MALAT1 is upregulated in multiple types of cancer and promotes tumor growth by a?ecting proliferation, invasion, and metastasis. Importantly, the region of MALAT1 that is su?cient to induce oncogenic activities includes the triple helix. Our work shows that the MALAT1 triple helix is

required for MALAT1 accumulation; therefore, we are currently exploring whether the triple helix plays a direct role in mediating oncogenic activities beyond its function as an RNA stability element.

Awards

NIH Pathway to Independence Award (K99/R00), 2014-2019 American Cancer Society Postdoctoral Fellowship, 2012-2014

OSU Presidential Fellowship, 2010

American Heart Association Predoctoral Fellowship, 2008- 2010

Selected Publications

Brown, J.A.; Steitz, J.A. “Intronless ß-globin reporter: a tool for studying nuclear RNA stability elements."Methods Mol. Biol.

2016, 1428, 77-92.

Brown, J.A.; Kinzig, C.G.; DeGregorio, S.J.; Steitz, J.A. “Hoogsteen-position pyrimidines promote the stability and function of the MALAT1 RNA triple helix." RNA 2016, 22(5),

743-749.

Brown, J.A.; Bulkley, D.; Wang, J.; Valenstein, M.L.; Yario, T.A.; Steitz, T.A.; Steitz, J.A. “Structural Insights into the Stabilization of MALAT1 Noncoding RNA by a Bipartite Triple Helix." Nat. Struct. Mol. Biol. 2014, 21(7), 633-640. Brown, J.A.; Valenstein, M.L.; Yario, T.A.; Tycowski, K.T.; Steitz, J.A. “Formation of Triple-Helical Structures by the 3"-End

Sequences of MALAT1 and MEN

 Noncoding RNAs." P. Natl.

Acad. Sci. USA 2012, 109(47), 19202-19207.

Brown, J.A.; Pack, L.R.; Fowler, J.D.; Suo, Z. “Pre-Steady State Kinetic Investigation of the Incorporation of Anti-Hepatitis B Nucleotide Analogues Catalyzed by Non-Canonical Human DNA Polymerases." Chem. Res. Toxicol.2012, 25, 225-233.

Professor

(574) 631-4659 brown.114@nd.edu Postdoctoral fellow, California Institute of Technology,

1994-96

PhD, Chemistry, University of Washington, 1994

BS, Chemistry, Massachusetts Institute of Technology, 1988

Inorganic and Organic Reaction Mechanisms:

Developing Catalysis for Energy and the

Environment

Enhancing our understanding of the mechanisms of chemical reactions is critical to improve processes that interconvert between chemical and electrical energy or to make chemical products in a selective and environmentally benign way. ?e Brown group is addressing this general problem by making new inorganic or organometallic complexes with the aim of achieving reactivity through novel mechanisms. Traditionally, oxidation-reduction reactions mediated by metal- containing compounds involve changes in both the oxidation state and bonding that directly involve those metal centers. We are exploring an alternative mode of redox reactivity, what we term “nonclassical" redox reactions, where bond-making or bond-breaking events occur at a metal center but oxidations or reductions occur not at the metal center but at redox-active ligands attached to the metal. ?ese processes generate novel species with unusual electronic structure, which may be capable of unusual reactivity. Furthermore, separating the locus of electron transfer from that of changes in bonding mimics the heterogeneous catalysis involved in fuel cells, suggesting that nonclassical homogeneous reactions may lead to conceptual insights or practical advances in systems for interconverting electrical and

chemical energy.In some cases, we have observed reactions where both the oxidation state changes and the bonding changes take place at the ligand rather than the metal. ?is has allowed us to observe reactions at coordinatively saturated or even encapsulated metal centers that would normally be considered poor choices as catalysts because of the unavailability of open sites at the metal. We are currently engaged in elucidating the e?ect of the metal-ligand bonding on this ligand-centered reactivity and using that information to design new catalysts with enhanced reactivity, selectivity, or durability.

Awards

Fellow of the American Chemical Society, 2011

University of Notre Dame Presidential Award, 2005

NSF CAREER Award, 1998-2002

Dupont Young Professor Award, 1998-2001

Camille and Henry Dreyfus Foundation New Faculty Award, 1996

Selected Publications

Marshall-Roth, T.; Brown, S.N. “Redox activity and  bonding in a tripodal seven-coordinate molybdenum(VI) tris(amidophenolate)." Dalton Trans. 2015, 44, 677-685. Shekar, S.; Brown, S.N. “Mechanism and Selectivity of Methyl and Phenyl Migrations in Hypervalent Silylated Iminoquinones." J. Org. Chem. 2014, 79, 12047-12055. Ranis, L.G.; Werellapatha, K.; Pietrini, N.J.; Bunker, B.A.; Brown, S.N. “Metal and Ligand Effects on Bonding in Group 6 Complexes of Redox-Active Amidodiphenoxides."

Inorg. Chem. 2014, 53 (19), 10203-10216.

Shekar, S.; Brown, S.N. “Mixed amidophenolate-

catecholates of molybdenum (VI)." Dalton Trans. 2014, 43 (9), 3601-3611. Cipressi, J.; Brown, S.N. “Octahedral to trigonal prismatic distortion driven by subjacent orbital pi antibonding interactions and modulated by ligand redox noninnocence."

Chem. Commun. 2014, 50 (59), 7956-7959.

Randolph, A.H.; Seewald, N.J.; Rickert, K.; Brown, S.N. “Tris(3,5-di-tert-butylcatecholato)molybdenum(VI): Lewis Acidity and Nonclassical Oxygen Atom Transfer Reactions." Inorg. Chem. 2013, 52 (21), 12587-12598. 1819
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Concurrent Professor

(574) 631-3024 mbruening@nd.edu chemistry .nd.educhemistry.nd.edu PhD, Chemistry, The Weizmann Institute of Science, 1995

MS, Chemistry, Brigham Young University, 1990

BS, Chemical Engineering, Brigham Young University, 1989

TITLE TITILE TITLE

Research in the Bruening group aims to create synthetic membranes for applications including water puri?cation and salt separations as well as protein capture, analysis, and digestion prior to mass spectrometry. In one area of this work, we grow polymer brushes and swollen polyelectrolyte ?lms in the pores of polymer membranes. When derivatized with metal-ion complexes, these coatings selectively bind multilayers of polyhistidine-tagged proteins to facilitate their puri?cation. ?e ?lms greatly increase protein-binding capacity, and the small pores in the membranes reduce di?usion distances to allow rapid protein adsorption. New spin membranes are now a commercial product, and current work focuses on selectively capturing therapeutic antibodies for rapid analysis. In a second area, we employ alternating adsorption of polycations and polyanions to form ultrathin separation membranes on highly porous supports. Judicious selection of the constituent polyelectrolytes in these ?lms a?ords membranes that selectively pass speci?c ions, e.g. K+/Mg2+ selectivities are >1000. Target applications include water softening and salt puri?cation, and the ultrathin ?lms allow these separations to occur at low pressures to reduce energy costs. Current research focuses on the combination of electrical potentials, ion-exchange membranes and ultrathin ?lms to enhance ion separations. ?e ?nal focus of our research is development of membranes containing catalytic enzymes. Layer-by-layer adsorption of polyanions and positively charged enzymes creates membranes that rapidly digest proteins prior to their analysis by mass spectrometry (MS). Variation of the ?ow rate through an enzyme- containing membrane controls the size of the resulting proteolytic peptides, and large peptides are particularly attractive for obtaining high sequence coverages when characterizing antibody modi?cations. Additionally, limited digestion can provide information on protein structure by demonstrating which regions of a protein are most accessible to an enzyme. All of these projects require thorough surface characterization. To investigate ultrathin ?lms and their properties, we employ atomic force microscopy, ?eld-emission scanning electron microscopy,

ellipsometry, electrochemical techniques, grazing angle re?ectance infrared spectroscopy, X-ray photoelectron spectroscopy, contact-angle measurements, and permeation experiments.

Awards

Benedetti-Pichler Award of the American Microchemical

Society, 2016

Michigan State University Innovation of the Year, 2015 Society for Electroanalytical Chemistry Young Investigator

Award, 2000

Selected Publications

J. Dong, W. Ning, W. Liu, and M.L. Bruening “Limited Proteolysis in Porous Membrane Reactors Containing Immobilized

Trypsin" Analyst 142, 2578-2586 (2017).

Y. Zhu, M. Ahmad, L. Yang, M. Misovich, A. Yaroshchuk, and M.L. Bruening “Adsorption of Polyelectrolyte Multilayers Imparts High Monovalent/Divalent Cation Selectivity to Aliphatic Polyamide Cation-exchange Membranes" J. Membr.

Sci. 537, 177-185 (2017).

S. Wijeratne, W. Liu, J. Dong, W. Ning, N.D. Ratnayake, K.D. Walker, and M.L. Bruening “Layer-by-layer Deposition with Polymers Containing Nitrilotriacetate, A Convenient Route to Fabricate Metal- and Protein-Binding Films" ACS Appl. Mater.

Interfaces 8, 10164-10173 (2016).

A. Yaroshchuk, Y. Zhu, M. Bondarenko, and M.L. Bruening “Deviations from Electroneutrality in Membrane Barrier Layers: A Possible Mechanism Underlying High Salt Rejections" Langmuir 32, 2644-2658 (2016).

Y. Pang, W.-H. Wang, G.E. Reid, D.F. Hunt, and M.L. Bruening, “Pepsin-Containing Membranes for Controlled Monoclonal Antibody Digestion Prior to Mass Spectrometry Analysis"

Anal. Chem. 87, 10942-10949 (2015).

Concurrent, Henry Massman Professor

of Civil Engineering

Director, Center for Sustainable

Energy at Notre Dame

(574) 631-7852 pburns@nd.edu

PhD, Geology, University of Manitoba, 1994

MSc, Geology, University of Western Ontario, 1990

BSc, Geology, University of New Brunswick, 1988

Environmental and Actinide Chemistry

Burns' research focuses on actinide chemistry and geochemistry, mostly involving uranium, neptunium, and thorium. Applications of the research include understanding transport of actinides in the environment, environmental remediation, nano-scale control of actinides to support an advanced nuclear energy system, the geologic disposal of nuclear waste, and nuclear forensics for national security. Central to the focus of the group is the synthesis and characterization of complex actinide materials in solution and the solid state using X-ray diffraction, X-ray scattering, and various spectroscopic techniques.

Awards

President of Mineralogical Association of Canada, 2008- 2012
Vice president of the Mineralogical Association of Canada,

2006-2008

Mineralogical Society of America Award and life fellow, 2001
Donath Medal of the Geological Society of America, 1999 Young Scientist Medal of the Mineralogical Association of

Canada, 1998

Hawley Medal (best paper award) of the Mineralogical

Association of Canada, 1997

Publications

Qiu, J.; Dembowski, M.; Szymanowski, J.E.S.; Toh, W.C.; Burns, P.C. “Time-Resolved X-ray Scattering and Raman

Spectroscopic Studies of Formation of a Uranium-

Vanadium-Phosphorus-Peroxide Cage Cluster." Inorg.

Chem. 2016, 55(14), 7061-7067.

Dembowski, M.; Olds, T.A.; Pellegrini, K.L.; Hoffmann, C.; Wang, X.P.; Hickam, S.; He, J.H.; Oliver, A.G.; Burns, P.C. “Solution P-31 NMR Study of the Acid-Catalyzed Formation of a Highly Charged {U(24)Pp(12)} Nanocluster, [(UO2)(24)(O-2)(P2O7)(12)](48-), and Its Structural Characterization in the Solid State Using Single-Crystal Neutron Diffraction." J. Am. Chem. Soc. 2016, 138(27),

8547-8553.

Miro, P.; Vlaisavljevich, B.; Gil, A.; Burns, P.C.; Nyman, M.; Bo, C. “Self-Assembly of Uranyl-Peroxide Nanocapsules in Basic Peroxidic Environments." Chem. Eur. J. 2016,

22(25), 8571-8578.

Gao, Y.Y.; Szymanowski, J.E.S.; Sun, X.Y.; Burns, P.C.; Liu, T.B. “Thermal Responsive Ion Selectivity of Uranyl Peroxide Nanocages: An Inorganic Mimic of K+ Ion Channels."

Angew. Chem. Int. Ed. 2016, 55(24), 6887-6891.

Wylie, E.M.; Peruski, K.M.; Prizio, S.E.; Bridges, A.N.A.; Rudisill, T.S.; Hobbs, D.T.; Phillip, W.A.; Burns, P.C. “Processing used nuclear fuel with nanoscale control of uranium and ultrafiltration." J. Nucl. Mater. 2016, 473,

125-130.

Soltis, J.A.; Wallace, C.M.; Penn, R.L.; Burns, P.C. “Cation- Dependent Hierarchical Assembly of U60 Nanoclusters into Macro-Ion Assemblies Imaged via Cryogenic Transmiision Election Microscopy." J. Am. Chem. Soc.

2016, 138(1), 191-198.

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JON CAMDEN

Associate Professor

(574) 631-1059 jon.camden@nd.edu Postdoctoral Researcher, Northwestern University, 2005-2008 PhD, Physical chemistry, Stanford University, 2005 BS, Chemistry and Music, University of Notre Dame, 2000

Fundamental Optical Properties of Metallic

Nanostructures

Research in the Camden group explores the fundamental optical properties of metallic nanostructures and applies this knowledge to develop new analytical methods. Our studies attempt to bridge the gap between physical and analytical chemistry. Areas of particular interest are: (1) ultrasensitive detection schemes for nuclear forensics and environmental pollutants, (2) the expansion of surface enhancement to nonlinear spectroscopies, and (3) using sub-nanometer plasmon imaging in the electron microscope to understand the response of plasmon-assisted catalysis. Throughout our work, we put a special emphasis on exploring systems that are amenable to high-level theoretical methods and making close connections with theoretical research groups. Many applications of plasmonic nanoparticles, of which surface enhanced spectroscopy is just one, require an intimate understanding of the nanoparticle LSPR. Electron energy loss spectroscopy (EELS) in the scanning transmission electron microscope (STEM) has emerged as a technique capable of mapping the energy and spatial distribution of plasmon modes at the nanometer scale. Our group uses the powerful combination of STEM/EELS and optical scattering to probe the plasmon response of metallic structures at the sub-nanometer level. These studies focus on understanding the response of substrates for surface-enhanced spectroscopy and plasmon-assisted catalysis. Two-photon transitions, for example, play an essential role in energy up-conversion, all-optical switching, optical data storage,

3D lithography, and biological imaging. While plasmonic

nanostructures have been utilized extensively to enhance linear spectroscopies, such as surface enhanced Raman scattering (SERS), almost no effort has been devoted to studying the enhancement of nonlinear spectroscopies, despite their potential impact. The Camden group is currently studying a prototypical nonlinear spectroscopy: surface enhanced hyper-Raman scattering (SEHRS). We have recently demonstrated single molecule sensitivity with SEHRS and discovered the surprising importance of non-Condon effects in common dye molecules such as

Rhodamine 6G by using SEHRS.

The large enhancement factors of SERS classify it as a highly

sensitive spectroscopy technique; thus, presenting SERS often The general applicability of SERS, however, is limited by environmental pollutants such as hydrazine.

Awards

Research and Creative Achievement Award, University of

Tennessee, 2013

NSF CAREER Award, 2012

NSF Graduate Research Fellowship, 2001

Selected Publications

Wu, Y.Y.; Li, G.L.; Cherqui, C.; Bigelow, N.W.; Thakkar, N.; Masiello, D.J.; Camden, J.P.; Rack, P.D. "Electron Energy Loss Spectroscopy Study of the Full Plasmonic Spectrum of Self-Assembled Au-Ag Alloy Nanoparticles: Unraveling Size, Composition, and Substrate Effects." ACS Photonics

2016, 3(1), 130-138.

Simmons, P.D.; Turley, H.K.; Silverstein, D.W.; Jensen, L.; Camden, J.P. "Surface-Enhanced Spectroscopy for Higher-Order Light Scattering: A Combined Experimental and Theoretical Study of Second Hyper-Raman Scattering." J. Phys. Chem. Lett. 2015, 6(24), 5067- 5071.

Gu, X.; Camden, J.P. "Surface-Enhanced Raman

Spectroscopy-Based Approach for Ultrasensitive and Selective Detection of Hydrazine." Anal. Chem. 2015,

87(13), 6460-6464.

Li, G.L.; Cherqui, C.; Wu. Y.Y.; Bigelow, N.W.; Simmons, P.D.; Rack, P.D.; Masiello, D.J.; Camden, J.P. "Examining

Substrate-Induced Plasmon Mode Splitting and

Localization in Truncated Silver Nanospheres with Electron Energy Loss Spectroscopy." J. Phys. Chem. Lett.

2015, 6(13), 2569-2576.

IAN CARMICHAEL

Professor

Director, Radiation Laboratory

(574) 631-4502 carmichael.1@nd.edu PhD, Physical and Theoretical Chemistry, University of Glasgow, Scotland, 1974 BSc (1st Class Hons.), Chemistry, University of Glasgow, Scotland, 1971

Quantum Chemistry of Reactive Intermediates

Molecular Magnetic Properties Theoretical

Radiation Chemistry

Ionizing radiation pervades our environment and affects all life on earth. The absorption of this impinging energy can produce profound chemical and biochemical transformations in the materials irradiated. Research at the Notre Dame Radiation Laboratory, the premier facility for radiation chemistry supported by the Division of Chemical Science, Geosciences and Biosciences, Basic Energy utilizes a unique constellation of experimental tools in a strong collaborative environment to build a fundamental molecular-level understanding of these interactions. for addressing challenges in, for example, capture and chemical conversion of solar energy, nuclear power generation, environmental waste management and remediation, and medical radiation therapies. Opportunities for focused interdisciplinary investigations are evidenced by the presence of graduate students drawn from the departments of chemistry and biochemistry, physics, and chemical and biomolecular engineering, in addition to student visitors from other national and international universities. Carmichael's work is centered on the application of quantum chemistry to unravelling the course of electron-driven processes in the condensed phase, such as excited state and radical formation Radiation effects in heterogeneous systems and at interfaces, such as those between water and ceramic oxides, are modeled. We also probe charge separation and transport in conjugated polymers, spin coupling in biomolecules, and radiation damage during macromolecular crystallography, a key roadblock in protein structure determination.Publications Bury, C.; McGeehan, J.E.; Antson, A.; Carmichael, I.; Gerstel, M.; Shevtsov, M.; Garman, E.F. "RNA protects a nucleoprotein complex against radiation damage." Acta

Crystallogr. 2016, D72, 648-657.

Hadad, M.J.; Zhang, W.; Turney, T.; Sernau, L.; Wang, X.; Woods, R.; Incandela, A.; Surjancev, I.; Wang, A.; Yoon, M-K.; Coscia, A.; Euell, C.; Meredith, R.; Carmichael, I.; Serianni, A.S. "NMR Spin-Couplings in Saccharides: Relationships Between Structure, Conformation, and the Magnitudes of JHH, JCH and JCC Values."NMR in Glycoscience and Glycotechnology, K. Katos and T. Peters,

Eds. 2016. Royal Society of Chemistry.

Bury, C.; Carmichael, I.; McGeehan, J.E.; Garman, E.F. "Radiation damage with nucleoprotein complexes studied by macromolecular X-ray crystallography." Radiat. Phys. Chem. 2016 [DOI 10.1016/j.radphyschem.2016.05.023] Bury, C.; Garman, E.F.; Ginn, H.M.; Ravelli, R.B.G.; Carmichael, I.; Kneale, G.; McGeehan, J.E. "Radiation damage to nucleoprotein complexes in macromolecular crystallography." J. Synchotron Radiat. 2015, 22, 213- 224.
Dawley, M.M.; Tanzer, K.; Carmichael, I.; Denifl, S.; Ptasinska, S. "Dissociative electron attachment to the gas-phase nucleobase hypoxanthine." J. Chem. Phys. 2015, 142,

21501.

2223
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FRANCIS J. CASTELLINO

Kleiderer/Pezold Professor,

Director, W.M. Keck Center for

Transgene Research

(574) 631-9152 castellino.1@nd.edu

Postdoctoral researcher, Duke University, 1968-70

PhD, Biochemistry, University of Iowa, 1968

MS, Biochemistry, University of Iowa, 1966

BS, Chemistry, University of Scranton, 1964

Structural Biology and

in vivo Mechanisms of

Blood Coagulation and Fibrinolysis

Professor Castellino's research involves the structure, function, and activation of proteins that participate in blood coagulation and blood-clot dissolution. The in vivo mechanisms of the roles of these proteins in these processes are being addressed through in vivo targeted gene-replacement approaches. Major tools being used include cloning, mutagenesis, and expression of variant recombinant proteins and individual protein domains, and immunochemical studies of the proteins, as well as physical and chemical analysis of their solution structures. Current work A streptococcus, which infects ~ 700M/annually, worldwide. Some strains of these bacteria number can disseminate in the body, leading to serious conditions of necrotizing faciitis, several cases of which hav recentlye received worldwide attention. Another project receiving attention emphasizes the structure- function relationships of small gamma-carboxyglutamic acid (Gla)-containing peptides from marine cone snails that target calcium into neuronal cells, this latter event being responsible for the neuropathology associated with stroke, epilepsy, Alzheimer's disease, ALS, etc. The biochemical, pharmacological, and neurobiological mechanisms of the actions of these peptides are being investigated. To determine the biological functions of genes encoding coagulation infection, wound healing, embryonic implantation and development, metastases, and atherosclerosis, gene deletion and other gene- targeting experiments are being performed in mice, in conjunction with phenotyping of these animals.

Awards

Editor-in-chief, Current Drug Targets, 2001-present Wyeth International Prize for contributions to firbrinolysis, 2008

Elected Fellow, American Heart Association, 2001

Elected Fellow, American Association for the Advancement of Science, 1988National Institutes of Health Research Career Development

Award, 1974-1979

Camille and Henry Dreyfus Teacher-Scholar Grant, 1974 Elected fellow of the New York Academy of Sciences, 1977

Selected Publications

Bao, Y.J.; Liang, Z.; Mayfield, J.A.; Donahue, D.L.; Carothers, K.E.; Lee, S.W.; Ploplis, V.A.; Castellino, F.J. "Genomic Characterization of a Pattern D Streptococcus pyogenes emm53 Isolate Reveals a Genetic Rationale for Invasive Skin Tropicity." J. Bacteriol. 2016, 198(12), 1712-1724. Mamczak, C.N.; Maloney, M.; Fritz, B.; Boyer, B.; Thomas, S.; Evancs, E.; Ploplis, V.A.; Castellino, F.J.; McCollester, J.; Walsh, M. "Thromboelastography in Orthopaedic Trauma Acute Pelvic Fracture Restoration: A Descriptive Pilot

Study." J. Orthop. Trauma 2016, 30(6), 299-305.

Agrahari, G.; Liang, Z.; Glinton, K.; Lee, S.W.; Ploplis, V.A.; Castellino, F.J. "Streptococcus pyogenes Employs Strain- dependent Mechanisms of C3b Inactivation to Inhibit Phagocytosis and Killing of Bacteria." J. Biol. Chem.2016,

291(17), 9181-9189.

Cheriyan, J.; Balsara, R.D.; Hansen, K.B.; Castellino, F.J. "Pharmacology of triheteromeric N-Methyl-D-Aspartate

Receptors." Neurosci. Lett. 2016, 617, 240-246.

Motley, M.P.; Madsen, D.H.; Jurgensen, H.J.; Spencer, D.E.; Szabo, R.; Holmbeck, K.; Flick, M.J.; Lawrence, D.A. Castellino, F.J.; Weigert, R.; Bugge, T.H. "A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo." Blood 2016, 127(9), 1085- 1096.

MAYLAND CHANG

Research Professor

Director, Chemistry Biochemistry-

Biology Interface (CBBI) Program

(574) 631-2965 mchang@nd.edu Postdoctoral Fellow, Columbia University, 1986-1988

PhD, Chemistry, University of Chicago, 1986

BS, Chemistry, University of Southern California, 1981 BS, Biological Sciences, University of Southern California, 1980

Biomedical Research, Drug Discovery

and Development, Drug Metabolism and

Pharmacokinetics

The Chang laboratory conducts biomedical research to understand the molecular basis of disease and to design small molecules for therapeutic intervention. Some of our current projects are described below. Chronic wounds are a complication of diabetes that results in >70,000 lower-limb amputations in the United States every year. The reasons for why diabetic wounds are recalcitrant to healing are not fully understood, and there is a single FDA-approved drug to treat diabetic foot ulcers; however it is associated with increased mortality and cancer. We used and related ADAMs coupled with quantitative proteomics to identify active MMP-8 and MMP-9 in diabetic wounds. Using the selective MMP-9 inhibitor ND-336 led to acceleration angiogenesis, and by re-epithelialization of the wound, thereby reversing the pathological condition. The detrimental role of was determined with a selective MMP-8 inhibitor and by topical application of the proteinase MMP-8. The combined topical application of ND-336 (a small molecule) and active recombinant MMP-8 (an enzyme) enhanced healing even more, in a strategy that holds considerable promise in healing of diabetic wounds. We are currently identifying and quantifying active MMPs in patients with diabetic foo