Presenter: Dr. Steven Firestine, Professor
Professor of Pharmaceutical Sciences
Department of Pharmaceutical Sciences
Eugene Applebaum College of Pharmacy and Health Sciences
Wayne State University
Abstract:
Antibiotics are arguably one of the greatest achievements in medical science, yet their utility is slowly being eroded by the rise of antibiotic resistant bacteria. To combat this problem, new antibiotics focused on novel targets are desperately needed. Unfortunately, the pharmaceutical industry has divested from antimicrobial drug discovery leaving only small biotechnology companies and academia to find the next generation of antibiotics. One approach is to focus on underexplored pathways that are different between microbes and humans. Previous research has shown that the de novo purine biosynthetic pathway is different in bacteria, yeast and fungi than it is in humans. The difference is centered on the synthesis of the intermediate carboxyaminoimidazole ribonucleotide (CAIR). CAIR is synthesized from aminoimidazole ribonucleotide (AIR) and in microbes, two enzymes are required. In contrast, humans need only one enzyme. Genetic studies have shown that deleting the genes necessary for CAIR synthesis in microbes renders them avirulent. The Firestine laboratory has been focused on the interesting biochemical differences in the enzymes responsible for CAIR synthesis as well as exploiting this dissimilarity in drug discovery. The laboratory has also been exploring agents to prevent the germination of C. difficile spores. C. difficile is a challenging infection that is commonly found in hospitals and nursing homes. Spore germination is regulated by bile salts and we have discovered potent bile salt analogs which prevent germination in the nanomolar range even while in the presence of millimolar concentrations of the germinate. This seminar will outline our research on these projects.
Biography:
Steve was born in Kalamazoo, MI and attended the University of Michigan where he majored in chemistry. While at UM, Steve conducted undergraduate research in the laboratory of Dr. James Coward working on the synthesis of fluorinated leucovorin. Steve graduated UM with high honors in chemistry and joined the Department of Medicinal Chemistry and Pharmacognosy at Purdue University where he studied medicinal chemistry and biochemistry under the direction of Dr. V. Jo Davisson. His doctoral studies focused on the study of AIR carboxylase and his research showed that this enzyme was different in microbes versus humans. Steve synthesized numerous nucleoside and nucleotide analogs including NAIR, which is the most potent inhibitor of AIR carboxylase known to date. Steve graduate in 1996 and conducted a Damon Runyon Walter Winchell Postdoctoral Fellowship in the laboratory of Dr. Stephen J. Benkovic at the Pennsylvania State University. Steve conduct research into protein engineering and the generation of artificial transcriptional switches. In 2000, Steve began his independent academic career as an assistant professor of medicinal chemistry at Duquesne University in Pittsburgh, PA. There, his research focused on DNA bending agents as a mechanism to control gene expression. In 2005, Steve moved to Wayne State University and he was promoted to full professor in 2016. Since his arrival at WSU, Steve has been continuously funded by the National Institutes of Health where his research has focused on antimicrobial drug discovery.
Presenter: Dr. Christopher Bowman, Distinguished Professor
James and Catherine Patten Endowed Chair Department of Chemical and Biological Engineering
Materials Science and Engineering Program
BioFrontiers Institute
Department of Restorative Dentistry
University of Colorado
Abstract:
Polymer networks possessing dynamic covalent crosslinks constitute a class of materials
with unique capabilities including the capacity for adapting to an externally applied
stimulus. These covalent adaptable networks (CANs) represent a paradigm in polymer
network fabrication aimed at the rational design of structural materials possessing
dynamic characteristics for specialty applications and functions. Here, we explore
several distinct approaches to CANs based on photochemically triggered responses.
First, those in which the reversible bond formation, based on addition-fragmentation,
occurs only during exposure to light will be discussed, enabling polymer network relaxation,
photoinduced actuation and shape memory effects, and stress relaxation. Using liquid
crystalline elastomer networks of this type, we will demonstrate the solution to fitting
a square peg into a round hole, reversibly. Secondly, using thiol-thioester exchange
chemistry, we will discuss the formation of a material that is capable of undergoing
a bistable transition from a viscoelastic solid to a viscoelastic fluid, induced by
light. Using this approach, we demonstrate recyclability, healing, and enhanced toughness
of materials based on these types of networks. Ultimately, the potential for CANs-based
materials to impact numerous materials applications will be presented in light of
their distinctive array of material properties.
Biography:
Professor Christopher N. Bowman received his BS and PhD in Chemical Engineering from Purdue University in 1988 and 1991, respectively. After receiving his PhD, he began his academic career at the University of Colorado in January of 1992 as an Assistant Professor. Since that time Professor Bowman has built a program focused on the fundamentals and applications of crosslinked polymers formed via photopolymerization reactions. He works in the broad areas of the fundamentals of polymerization reaction engineering, polymer chemistry, crosslinked polymers, photopolymerizations and biomaterials. Professor Bowman has remained at Colorado throughout his academic career and is currently the Patten Endowed Chair of the Department of Chemical and Biological Engineering as well as a Clinical Professor of Restorative Dentistry at the University of Colorado at Denver.
Presenter: Dr. Christo Z. Christov, Associate Professor
Associate Professor, Chemistry
Michigan Technological University
Abstract:
Mononuclear non-heme Fe(II) and 2-oxoglutarate (2OG)-dependent enzymes catalyze an incredibly diverse arsenal of chemical reactions with vital biological roles, making them attractive targets for therapeutics and biotechnology developments. Some of the chemical transformations performed by this family of enzymes include hydroxylation, demethylation, desaturation, and cyclization. One of the essential reactions performed by non-heme iron enzymes is histone demethylation. The class of enzymes responsible for histone lysine demethylation is called Histone Lysine Demethylases (KDMs). These enzymes couple decarboxylation of 2OG with substrate oxidation. Important demethylation reactions are catalyzed also by DNA demethylases such as the bacterial AlkB and its human homolog AlkBH2 in single-stranded (ss)- and double-stranded (ds) DNA. Also, an unusual enzymatic transformation performed by the Ethylene-Forming Enzyme (EFE) on its co-substrate (2OG) produces ethylene.
In this talk, I will present how applying state-of-the-art computational chemistry
methods such as molecular dynamics (MD) and Combined Quantum Mechanical/Molecular
Mechanical (QM/MM) we provide a mechanistic insight that cannot be received experimentally.
The discussion will focus on: i) the histone demethylases PHF8 (KDM7B) and KDM4A (JMJD2A),
which differ in their substrate specificity and domain organization; ii) DNA demethylases
AlkB and AlkBH2 that differ in their preference to ss- or ds DNA; and iii) the Ethylene-Forming
Enzyme (EFE) that performs a unique transformation of 2OG leading to the production
of ethylene. The atomic and molecular orbital interactions along the reaction process
within the enzyme environment will be discussed. The studies emphasize the critical
importance of the protein environment and dynamics, especially focusing on the second
sphere's interactions and beyond for the catalytic process. The outcomes contribute
to a fundamental understanding of enzyme mechanisms and have a long-term impact on
enzyme engineering and drug design.
Biography:
Dr. Christo Z. Christov grew up in the town of Sevlievo, Bulgaria. He received MSc in Biochemistry at University of Sofia, Sofia, and a PhD in Theoretical Chemistry at the Bulgarian Academy of Sciences, Sofia, Bulgaria. Following postdoctoral studies in Spain and the UK, Christo gained a tenured faculty position at the Department of Applied Sciences at Northumbria University, UK in 2010. He was awarded Fulbright Senior Grant and a Marie Curie International Outgoing Career Development Fellowship for the Department of Chemistry (The Solomon Lab) at Stanford University (2010-2013). Since 2017 Christo is an Associate Professor of Chemistry at the Department of Chemistry at Michigan Technological University, Houghton MI. Christo’s Research interests are in Computational Bioinorganic Chemistry with a focus on non- heme Fe(II) and 2OG-Dependent Oxygenase such as Histone Demethylases and TET enzymes involved in the epigenetic regulation and the Ethylene Forming Enzyme. Currently, Christo’s research is supported by the National Science Foundation of USA.
Presenter: Dr. Karana Shah, VP of Technology
Vice President of Technology
Dixie Chemical Company
Abstract:
From R&D scientist to technical marketing to company leadership, Karana Shah has had
an interesting career in industry since receiving her PhD from MSU in 2006. Taking
a leap from academia to industry can be a decision fraught with worry. Graduate students
and postdocs can have a tough time framing their extensive technical training into
tangible skills that employers are looking for. Job seekers at all levels want to
figure out if a position will be a good fit, with a company that will support future
growth and professional development. Karana will describe some of the steps she took
to find her first role out of graduate school and offer suggestions to those just
starting out. She has successfully moved between positions and companies several times
and will describe learnings from that process. At her current company, she has taken
on increased responsibility with a promotion to a senior leadership role. A solid
foundation with BS (2000) and MS (2002) degrees from MTU Chemistry helped lay the
groundwork for the path she is on today.
Biography:
Dr. Karana Shah joined Dixie Chemical in 2013 as Technical Services Manager and was promoted to VP of Technology in 2016. Prior to joining Dixie, she worked for Zoltek (now part of Toray Group), a global manufacturer of carbon fiber. At Zoltek, she supported the Composite Intermediates product line including pultruded profiles and prepreg. Karana also previously worked for Evonik Jayhawk Fine Chemicals as Technical Service Marketing Manager for Specialty Anhydrides and for TAMKO Building Products as a Research and Development Engineer for thermoplastic composite products. Dr. Shah earned her BS and MS degrees in Chemistry from Michigan Technological University in Houghton, MI. Her MS degree was completed under the guidance of Dr. Patricia Heiden in 2002. She also earned her PhD in polymer composites with advisor Dr. Laurent Matuana from the Department of Forestry at Michigan State University, East Lansing, MI in 2006.
Presenter: Dr. de Bettencourt-Dias, Professor
Susan Magee & Gary Clemons Professor of Chemistry
University of Nevada, Reno
Abstract:
The luminescence of lanthanide ions is based on f-f transitions. Due to the core nature
of the 4f orbitals involved in the process, as well as the forbidden nature of these
transitions, the emission properties make these ions uniquely suited for a variety
of applications involving light emission, such as lighting, imaging, and sensing.
Since the f-f transitions are forbidden, the emission is most efficiently promoted
through coordinated chromophores. The use of these coordinated ligands provides unique
opportunities. They can be functionalized to tailor the chemical and photophysical
properties of the resulting complexes.1 We have used this approach to synthesize complexes
that can be used as imaging agents for cancer cells.2 By extending the conjugation
of the ligand we shifted the excitation wavelengths into the visible and isolated
complexes that can be used as molecular nanothermometers.3 In addition, we used carbazole-based
ligands that enabled excitation of the resulting complexes in the biological window
by a two-photon process. Finally, we used oligothiophene-based ligands to isolate
complexes that luminesce and generate singlet oxygen.
In this presentation, I will discuss my group’s recent work on lanthanide ion complexes with dual activity, as well as some recent results on unusual coordination chemistry4-5 of these fascinating metal ions.
Figure 1. Temperature-dependent emission spectrum of K3[Tb(dipicCbz)3]. Inset shows
the intensity of the 5D4 → 7F5 transition as a function of temperature.3
References:
1. Luminescence of Lanthanide Ions in Coordination Compounds and Nanomaterials. de
Bettencourt-Dias, A., Ed. John Wiley and Sons: 2014.
2. Monteiro, J. H. S. K.; Machado, D.; de Hollanda, L. M.; Lancellotti, M.; Sigoli,
F. A.; de Bettencourt-Dias, A., Selective Cytotoxicity and Luminescence Imaging of
Cancer Cells with A Dipicolinato-based EuIII Complex Chem. Commun. 2017, 53, 11818-11821.
3. Monteiro, J. H. S. K.; Sigoli, F. A.; de Bettencourt-Dias, A., A Water-soluble
TbIII complex as temperature-sensitive luminescent probe. Can. J. Chem. 2018, 96,
859-864.
4. de Bettencourt-Dias, A.; Beeler, R. M.; Zimmerman, J. R., Anion-π and H-Bonding
Interactions Supporting Encapsulation of [Ln(NO3)6/5]3-/2- (Ln=Nd,Er) with a Triazine-based
Ligand. J. Am. Chem. Soc. 2019, 141, 15102-15110.
5. de Bettencourt-Dias, A.; Beeler, R. M.; Zimmerman, J. R., Secondary-Sphere Chlorolanthanide(III)
Complexes with a 1,3,5-Triazine-Based Ligand Supported by Anion-- ,, and Hydrogen-Bonding
Interactions. Inorg. Chem. 2020, 59, 151-160.
Biography:
Ana de Bettencourt-Dias received her ‘licenciatura’ (MS equivalent) in Technological
Chemistry from the University of Lisbon in 1993, and her ‘Dr. rer. nat.’ (PhD equivalent)
in Inorganic Chemistry from the University of Cologne in 1997 with Prof. Thomas Kruck.
In her graduate work, she isolated new titanium complexes as single source precursors
for the chemical vapor deposition of TiN thin layers. She joined the group of Prof.
Alan Balch at UC Davis in 1998 as a Gulbenkian postdoctoral fellow, where she studied
the electrochemistry and structure of fullerenes and endohedral fullerenes. In 2001
she joined the faculty at Syracuse University and started her work on luminescent
lanthanide ion complexes. She moved to the University of Nevada, Reno, as associate
professor in 2007 and was promoted to professor in 2013. Her research centers on light-emitting
compounds and coordination chemistry of the fblock of the periodic table. She served
on the editorial advisory board for Inorg. Chem. from 2013 to 2015, and has been a
managing member of the editorial board of the Journal of Rare Earths since 2014. She
was program chair of the 2011 and conference chair of the 2014 Rare Earth Research
Conference, organizes the lanthanides and actinides symposia at the national meetings
of the American Chemical Society and was the 2019 Chair of the Division of Inorganic
Chemistry of the American Chemical Society. She served as the Associate Vice President
for Research at UNR from 2015 to 2019. She returned to being a full-time faculty in
July 2019, and is now the Susan Magee & Gary Clemons Professor of Chemistry.
Presenter: Dr. Joseph J. Pignatello, Chief Scientist
The Connecticut Agricultural Experimental Station
Abstract:
Pyrogenic carbonaceous materials (PCM) are solid products of pyrolysis or thermolysis of biomass. Chars from wildfires, crop residue burning, or land clearing practices are widely distributed in the environment, and may influence soil structure, microbial activity, and behavior of pollutants especially in highly impacted areas. Produced PCMs such as activated carbon, biochar, and related materials, are in use or under study as agents in water, soil, and air purification, and as additives to improve soil properties. Central to the behavior of PCMs is their role as adsorbents; however, PCMs and their physico-chemically modified forms, are attracting interest as electron-transfer mediators and catalyst substrates. This lecture will describe our recent efforts in understanding and manipulating sorptive functions, probing the inherent chemical reactivity of PCMs and their ability to mediate electron-transfer reactions, and the modification of PCMs for specific environmental remediation functions.
Biography:
Dr. Pignatello has been a pioneer in Environmental Science, and currently is Chief Scientist at The Connecticut Agricultural Experimental Station There, he leads the Environmental Chemistry Group, which researches both fundamental and applied aspects of the environmental chemistry of pollutants and natural processes, such as physical-chemical processes for removing or degrading pollutants in soil, water and air, physical-chemical interactions of organic compounds with soils and soil components, and bioavailability of organic contaminants in natural particles. A recent research focus is studying the nature of the interactions between organic compounds and pyrogenic carbon, including studies of novel interactions between the carbons and behaviors, tailoring the carbon surfaces to adsorb and transform contaminants, and potential roles for these carbons in environmental management.
Presenter: Dr. Bradley D. Smith, Professor
Emil T. Hofman Professor of Chemistry and Biochemistry
University of Notre Dame
Abstract:
The lecture will describe new families of near-infrared absorbing molecular probes. Cell microscopists have a need for fluorophores with high photostability, extreme brightness, low phototoxicity, and user friendly bioconjugation. In contrast, in vivo imaging researchers and fluorescence guided surgeons strongly prefer fluorescent probes that emit low energy near-infrared light since it can penetrate through skin and tissue. A family of interlocked molecules called Squaraine-Rotaxanes are valuable as extremely bright and stable deep-red fluorescent probes and they are being used increasingly for single molecule tracking studies. A new dye architecture called Squaraine Figure-Eight enables insertion of peptide units into the probe structure to create targeted probes. Another new probe system is based on sterically shielded near-infrared heptamethine cyanine dyes that have unsurpassed performance properties such as high stability and low propensity for non-specific interaction with biological surfaces. Bioconjugates of these shielded heptamethine cyanine dyes include antibody and peptide systems with superb bioimaging performance in cells and in living subjects.
Biography:
Bradley D. Smith is the Emil T. Hofman Professor of Chemistry and Biochemistry at the University of Notre Dame, Indiana, USA. He is also Director of the Notre Dame Integrated Imaging Facility that supports university imaging research. He is the author of 260 research publications and Associate Editor of the ACS journal Bioconjugate Chemistry. His research group develops molecular probes for detecting and treating cancer or microbial infections in living subjects. Dr Smith has invented a series of near-infrared fluorescent dye molecules and converted them into imaging probes for a wide range of applications in biomedical science, biotechnology, and nanotechnology.
Presenter: Zhenan Bao, Professor
K.K. Lee Professor and Department Chair in the Department of Chemical Engineering
Stanford University
Courtesy Professor in the Department of Chemistry and Department of Materials Science
and Engineering
Director of Stanford Wearable Electronics Initiative (eWEAR)
Abstract:
Image of stretchable electronic skin. Image credit: Amir Foudeh, Sihong Liu of Bao
Group, Stanford University.
Skin is the body’s largest organ, and is responsible for the transduction of a vast
amount of information. This conformable, stretchable, self-healable and biodegradable
material simultaneously collects signals from external stimuli that translate into
information such as pressure, pain, and temperature. The development of electronic
materials, inspired by the complexity of this organ is a tremendous, unrealized materials
challenge. However, the advent of organic-based electronic materials may offer a potential
solution to this longstanding problem. Over the past decade, we have developed materials
design concepts to add skin-like functions to organic electronic materials without
compromising their electronic properties. These new materials and new devices enabled
arrange of new applications in medical devices, robotics and wearable electronics.
In this talk, I will discuss several projects related to engineering conductive materials
and developing fabrication methods to allow electronics with effective electrical
interfaces with biological systems, through tuning their electrical as well as mechanical
properties. The end result is a soft electrical interface that has both low interfacial
impedance as well as match mechanical properties with biological tissue. Several new
concepts, such as “morphing electronics” and “genetically targeted chemical assembly
- GTCA” will be presented.
Biography:
Zhenan Bao is Department Chair and K.K. Lee Professor of Chemical Engineering, and by courtesy, a Professor of Chemistry and a Professor of Material Science and Engineering at Stanford University. Bao founded the Stanford Wearable Electronics Initiate (eWEAR) in 2016 and serves as the faculty director.
Prior to joining Stanford in 2004, she was a Distinguished Member of Technical Staff in Bell Labs, Lucent Technologies from 1995-2004. She received her Ph.D in Chemistry from the University of Chicago in 1995. She has over 550 refereed publications and over 65 US patents with a Google Scholar H-Index >160.
Bao is a member of the National Academy of Engineering and the National Academy of Inventors. She is a Fellow of MRS, ACS, AAAS, SPIE, ACS PMSE and ACS POLY.
Bao was selected as Nature’s Ten people who mattered in 2015 as a “Master of Materials” for her work on artificial electronic skin. She was awarded the inaugural ACS Central Science Disruptor and Innovator Prize in 2020, the Gibbs Medal by the Chicago session of ACS in 2020, the Wilhelm Exner Medal by Austrian Federal Minister of Science 2018, ACS Award on Applied Polymer Science 2017, the L'Oréal-UNESCO For Women in Science Award in the Physical Sciences 2017, the AICHE Andreas Acrivos Award for Professional Progress in Chemical Engineering in 2014, ACS Carl Marvel Creative Polymer Chemistry Award in 2013, ACS Cope Scholar Award in 2011, the Royal Society of Chemistry Beilby Medal and Prize in 2009, the IUPAC Creativity in Applied Polymer Science Prize in 2008.
Bao is a co-founder and on the Board of Directors for C3 Nano and PyrAmes, both are silicon-valley venture funded start-ups. She serves as an advising Partner for Fusion Venture Capital.
Presenter: Dr. Clint P. Aichele, Associate Professor and Lew Ward Faculty Fellow
School of Chemical Engineering
Oklahoma State University
Abstract:
Proteins are incredibly useful in medicine and industrial chemistry. Many of the most recent breakthroughs in cancer therapy are based on monoclonal antibody treatments. Yet, there are major difficulties that can act as deterrents in developments of such therapies. Sustained subcutaneous, oral or pulmonary deliveries of such therapeutics are limited by the poor stability, short half-life, and non-specific interactions between the therapeutic biomolecules (e.g. antibody) and the delivery vehicle. Similarly, usage of proteins as enzymes in processes is limited by poor stability, short half-life, and difficulties with reusability. With growing usage of proteins as pharmaceuticals and biocatalysts, and apparent shortcomings in both fields, there is a growing need to design materials that are protein compatible and can improve protein stability. The key to successfully utilizing proteins as therapeutics, biocatalysts or biosensors is to maintain their conformation and function. There is emerging evidence that biomimetic, biocompatible zwitterionic polymers can prevent non-specific interactions within proteins systems and increase protein stability. For the purpose of protein delivery, a biodegradable zwitterionic poly(carboxybetaine) based microscale hydrogel (microgel) was synthesized. The resulting microgels were characterized via FTIR, diffusion NMR, SANS, and cell culture studies. We examined a novel post-fabrication technique that resulted in effective loading of IgG in the microgels. The released antibodies (especially from the high crosslinked microgels) proved to be completely active and able to bind with antibody receptors. Furthermore, for the purpose of protein immobilization, reaction a scheme was developed and studied for covalent immobilization of the protein (α-chymotrypsin) (ChT) within the zwitterionic microscale hydrogels. This research paves the way for designing protein delivery vectors as well as fabrication of enzyme immobilized materials with extended enzyme lifetime and activity.
Biography:
Dr. Clint P. Aichele is an Associate Professor and Lew Ward Faculty Fellow in the School of Chemical Engineering at Oklahoma State University. Dr. Aichele's research is in the area of colloids and interfacial phenomena with specific applications in gas/liquid separation, emulsions, enhanced oil recovery, distillation, and flow assurance. His work specifically focuses on engineering interfaces to solve separation challenges in complex fluids. Dr. Aichele received his BS in Chemical Engineering from OSU in 2004 and PhD from Rice University in 2009. Dr. Aichele worked at ConocoPhillips as a Research Engineer for 3 years in the CO2 Capture and Avoidance group prior to joining the faculty at Oklahoma State University.
Presenter: Patrick Tomco, Assistant Professor
Assistant Professor/ASET Lab Coordinator
Department of Chemistry
University of Alaska Anchorage
Abstract:
Oil and gas drilling have been occurring in Alaska since the 1950s, and additional lease sales are planned for Cook Inlet and the Beaufort Sea. As regions in the Arctic become ice-free, offshore drilling in that area is expected to increase. As petroleum development increases, so does the risk of another major oil spill. Oil spills can have a devastating effect on the marine environment, and dispersants, chemical herders, and in-situ burning are supposed to mitigate that effect. Despite some of the benefits this technique appears to have on oil spill mitigation, opinions on the utilization of these strategies are polarized, and the issue requires careful consideration and study. This talk will focus on several recent investigations aimed at characterizing hydrocarbon-derived dissolved organic matter (DOMHC), photochemical products of DOMHC, photo-modified DOMHC bioavailability, and resulting toxicity potential of DOMHC to Arctic marine aquatic life (mussels, Mytilus trossulus). Characterization methods include Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS), fluorescence excitation emission matrices (EEMs), toxicity biomarkers, 16S rRNA sequencing, and NMR-based metabolomics.
Biography:
Patrick Tomco, Ph.D is an Assistant Professor of Chemistry at the University of Alaska
Anchorage, Chair of the Alaska ACS Local Section, and manager of the Applied Science
Engineering and Technology (ASET) laboratory.
Presenter: Blake R. Peterson, Chair and Professor
Division of medicinal Chemistry and Pharmacognosy
Ohio State University
John W. Wolfe Chair in Cancer Research
Co-Leader, OSUCCC Translational Therapeutics Program
Co-Director, OSUCCC Medicinal Chemistry Shared Resource
Abstract:
Phenotypic drug discovery represents an important approach for the identification
of therapeutics because it does not require extensive knowledge of a specific drug
target or mechanism of action. We are using this approach in conjunction with the
synthesis of molecular probes that accumulate in specific organelles to discover novel
anticancer agents and tool compounds. In this seminar, I will describe the use of
this phenotypic discovery / subcellular targeting strategy to identify small molecule
anticancer agents. The organelle that we are targeting with these probes is the endoplasmic
reticulum (ER), which is defined by an extensive network of intracellular membranes
and plays critical roles in the processing of secreted and transmembrane proteins.
To deliver small molecules to membranes of this organelle, we synthesized novel fluorinated
fluorophores derived from a fluorophore that we previously reported termed Pennsylvania
Green. I will describe how these compounds can be used to inhibit a specific protein
processing pathway controlled by the ER, and how we built on this molecular platform
to create uniquely sensitive sensors of the reactive nitrogen species peroxynitrite,
which contributes to immunosuppression in cancer. We further used an optimized peroxynitrite
sensor in a phenotypic drug discovery campaign to identify small molecules capable
of blocking the production of this reactive species in immune cells prevalent in the
tumor microenvironment. This approach could lead to novel small molecule inhibitors
and repurposing of existing drugs as therapeutics that help overcome immunosuppression
in cancer.
Biography:
Blake Peterson was raised in Reno, Nevada. After receiving a BS in Chemistry from the University of Nevada Reno in 1990, he pursued a PhD in Chemistry with Prof. François Diederich at UCLA. During his graduate training, he moved with Prof. Diederich to Switzerland, where he conducted research for two years at the ETH-Zurich. In 1994, he accepted a postdoctoral position with Prof. Gregory Verdine in the Dept. of Chemistry and Chemical Biology at Harvard University as a Damon Runyon / Walter Winchell Cancer Research Foundation Fellow. In 1998, he joined the faculty in the Dept. of Chemistry at Penn State University as an Assistant Professor and was promoted to Associate Professor with tenure in 2004. During this time, he was named a research scholar of the American Cancer Society in 2003 and was the recipient of a Camille Dreyfus Teacher Scholar Award in 2004. In 2008, he joined the faculty of the Department of Medicinal Chemistry at the University of Kansas as Regents Distinguished Professor and was named an Eminent Scholar by the Kansas Biosciences Authority. In 2013, he was elected as a fellow of the American Association for the Advancement of Science (AAAS). In 2019, he joined the faculty of The Ohio State University College of Pharmacy as Professor and Chair of the Division of Medicinal Chemistry and Pharmacognosy. He additionally holds appointments at the Ohio State University Comprehensive Cancer Center as John W. Wolfe Chair in Cancer Research, Co-Leader of the Translational Therapeutics Program, and Co-Director of the Medicinal Chemistry Shared Resource. His current research interests involve the pursuit of new strategies for early-stage anticancer drug discovery.