Category: Schaus, Scott

Boston University Chemistry 2015-2016 Academic Year Grant Awards

July 14th, 2016 in Beeler, Aaron, Doerrer, Linda, Elliott, Sean, Grants, Grants & Funding, Grinstaff, Mark, Jeffries-EL Malika, Malika, NIH, NSF, Perlstein, Deborah, Porco, John, Reinhard, Björn, Research, REU, Schaus, Scott, Snyder, John, Straub, John, Tullius, Tom, Uncategorized, Ziegler, Larry

The Chemistry Department is one of the most active research departments at Boston University. With 24 research active faculty involved in many different focus areas, we are committed to a research active learning environment where our faculty and students are afforded the opportunity to do cutting edge chemical research.  In order to continue to build on our strong research focus, our faculty have submitted over 30 grant proposals during the 2015-2016 academic year, with 20 of them being awarded totaling over $5 million in new funding this year alone.

Below is a list of the awarded grant proposals as well as their abstracts.  For more information about the Faculty member who will the the Principal Investigator please click on their name.

 

Boston University Chemistry Department Awarded Grants Academic Year 2015-2016

 

Scott Schaus, National Institute of Health / National Institute of General Medical Science

Enantioselective Catalytic Boronate Reactions

The development of new chemical methodologies is an important objective of organic synthesis. An area that continues to inspire chemists is the chemistry of organoboranes and boronates. The unique properties of boron and the ability to activate organic boronates to deliver carbon nucleophiles has yielded an impressive array of chemical methods and processes. We will extend the ability of organoboranes and boronates to deliver carbanion equivalents in novel condensation reactions including chemoselective carbonyl condensations and multicomponent reactions. The reactions will be rendered asymmetric through the development of asymmetric catalysts and chiral boronate reagents and the utility of the methods developed demonstrated by the asymmetric synthesis of pharmaceuticals and natural products. Significant advances have been made in the mechanistic understanding of boronate activation via ligand exchange with chiral diols. We will use the mechanistic insight we have obtained to expand the repertoire of reactions catalyzed by dynamic ligand exchange processes to include acyl cyanides as electrophiles, borono-Petasis reactions, and ortho-quinone methide chemistry. Our continued interest in reaction discovery has led to the identification of chiral diol acid catalysts capable of promoting the enantioselective addition reactions to acetals. We seek to explore this reactivity and expand it to include types of functionalized nucleophiles in additions to oxoniums and iminiums and boronate hetero-Diels–Alder reactions. Goals of the research program include developing a breadth of reactivity, providing access to novel chiral blocks, and new reaction development. Bond constructions are selected to access chiral synthetic intermediates that could be used in the construction of pharmaceuticals and natural products. The results will transform the way boronate nucleophiles are utilized in enantioselective synthesis.

 

John Straub, National Institute of Health

Probing the role of membrane and cholesterol on APP-C99 structure and dynamics

Aggregation of proteins of known sequence is linked to a variety of neurodegenerative disorders. Familial mutations in the Amyloid Precursor Protein (APP), from which the amyloid β (Aβ) protein associated with Alzheimer’s Disease (AD) is derived, have been linked with the early onset of amyloid disease.

With this computational and theoretical research grant, augmented by synergistic experimental research collaborations, we will determine the structure and dynamics of the 99 amino acid transmembrane fragment of APP (APP-C99) in membrane environments in order to address fundamental biophysical questions articulated in three Specific Aims. (1) We will explore how length, sequence, and membrane composition influence the structure of the APP-C99 monomer. (2) The structures of APP-C99 dimers and the associated stability as well as the monomer-dimer equilibrium are also influenced by membrane composition and C99 sequence. We will investigate the influence of these environmental factors on the structure and dynamics of dimer formation. (3) We will also determine how APP-C99 interacts with cholesterol and cholesterol-analogs, as well as how those interactions influence APP-C99 structure and dimerization.

 

Larry Ziegler & Bjoern Reinhard, National Science Foundation

Plasmonically Enhanced Stimulated Coherent Spectroscopy

There is growing interest in using plasmonics to enhance and control chemistry on surfaces for applications such as chemical catalysis, pollution mitigation and energy conversion. The proposed time-domain experiments are aimed at developing a better dynamical and structural description of how molecules interact with plasmonic materials. Differences in energy fluctuation timescales, interaction strengths and energy distributions are anticipated for molecules on plasmonic surfaces as compared to molecules in liquid solutions. Characterizations of these properties are central to understanding chemical activity occurring on these substrates. Plasmonically enhanced stimulated coherent vibrational and electronic spectroscopic measurements of analytes on plasmonic substrates will be obtained to learn about these interactions. Fabricated metal nanoparticle cluster arrays will be employed here. This substrate type provides a wide range of design parameters that will be used to maximize signal strengths and robustness for the planned studies. The proposed research effort will be carried out by two Boston University PIs with complementary expertise in ultrafast spectroscopy and nanoscience.

 

Tom Tullius, National Science Foundation

Chemical probing of RNA tertiary structure in a whole transcriptome at singleatom resolution

RNA (ribonucleic acid) is now widely appreciated to be a key participant in nearly all of the activities of the cell, yet we have limited information on the three-dimensional structures of most RNA molecules. This presents a challenge, because we know that the biological function of an RNA molecule depends on its structure. To understand the relationship between structure and function for the large number of RNA molecules that populate the cell, new high-throughput experimental approaches for structure determination are needed. The aim of this project is to develop a new experimental method that can provide detailed information on the three-dimensional folding of all the RNA molecules in a cell, in one experiment. The new method combines chemical probing of RNA structure by the hydroxyl radical, the quintessential Reactive Oxygen Species, with analysis by high-throughput sequencing, so that the structures of all RNA molecules in a cell can be monitored simultaneously.

 

John Porco, National Institute of General Medical Science

Chemical Synthesis of Complex Natural Products for Translational Science

The National Institutes of Health, Institute of General Medical Sciences (NIGMS), has awarded Professor John Porco and coworkers (http://sites.bu.edu/porcogrp/) a five year MIRA (R35) grant entitled “Chemical Synthesis of Complex Natural Products for Translational Science.”  The Maximizing Investigators’ Research Award (MIRA-R35), an Outstanding Investigator Award, is a grant that provides support for all of the research in an investigator’s laboratory that falls within the mission of NIGMS. Within these bounds, investigators have the freedom to explore new avenues of inquiry that arise during the course of their research. The goals of the MIRA (R35) research program are to continue chemical syntheses of bioactive molecules and expand efforts and capabilities in translational science. The MIRA effort effectively replaces two previous NIGMS-funded RO1 grants (Biomimetic Synthesis of Complex Natural Products (GM-073855) and Chemical Synthesis of Bioactive Flavonoid and Xanthone-Derived Natural Products (GM-099920) which were highly productive and led to 41 publications from 2010 – 2015. As part of the MIRA project, the Porco group will continue development of novel synthetic methodologies for concise entry to bioactive classes of natural products including oxaphenalenones, meroterpenoids, polyprenylated acylphloroglucinols, tetrahydroxanthones, and dimeric chromones. The project will also continue major emphasis on collaborations to study biological properties and mode of action (MoA) of target molecules for ultimate use as pharmacological therapies for human cancers as well as viral and bacterial illnesses.

 

Malika Jefferies-EL, National Science Foundation

Early Career Investigator Workshop
In an effort to develop the next generation of Chemistry researchers, the National Science Foundation Division of Chemistry has sponsored the proposal of Professor Malika Jeffries-EL and co-PI Jeff Moore for the University of Illinois-Urbana Champagne to hold an NSF Chemistry Early Career Investigator Workshop. The objective of these workshops is to provide early career chemist with networking opportunities and relevant information needed to better assess their research ideas, projects, and plans so as to more effectively compete for grant applications to the NSF CAREER program, other NSF programs and other federal agencies. The workshop was held March 10th-11th 2016 in Arlington VA at the Hilton Garden Inn, which is close to the NSF headquarters, enabling the participation of many program officers. The workshop is had approximately 120 participants and will be open to investigators performing research in NSF-supported disciplines within the United States. While the workshop is primarily intended for junior faculty members, advanced graduate students, postdocs, and other research scientist.

 

Ksenia Bravaya, Boston University

Patrick Mclellan Leavitt Research Award

This award is designed “to support research of one or more non-tenured junior faculty members, or graduate students, in chemistry or biology at the College of Arts and Sciences. Preference shall be given to female faculty who demonstrate a commitment to encouraging women to study science, or to female graduate students.”

Dr. Bravaya will use these funds to support her research into challenging electronic structure phenomena in biomolecules and systems relevant for materials, which include photoinduced processes, autoionizing electronic states, and magnetic field effects. This award will help her and her team use and develop high-level electronic structure methods targeting processes involving multiple electronic states, chemistry of open-shell species in magnetic fields, and electronically excited and metastable systems.

 

Mark Grinstaff, National Science Foundation

SusChEM: Glycerol Polycarbonates as New Biomaterials

The future development of medical devices. Scientific advances, such as those described in this NSF sponsored research, will support US industries, which play an important role in this medical polymers market estimated to exceed $3.5 billion by 2018. This grant support undergraduate students and graduate students, who will benefit from an interdisciplinary cutting-edge research and educational experience that encompasses training in biomaterials and polymer chemistry. Students will be encouraged to think independently and creatively while recognizing the importance of collaborating with other experts (e.g., materials scientists, pathologist, biomedical engineers, and patent lawyers). These activities will contribute to positive societal outcomes by fostering excitement for basic research while educating and training a future workforce.

In the biomaterials and biomedical field, degradable polymers such as poly(lactic acid) and poly(glycolic acid) are widely studied and are an integral component of many medical device products. Although extensively used, these poly(hydroxy acid)s possess a number of limitations including: 1) limited capability for backbone functionalization; 2) acidic products upon degradation; and 3) poor control over molecular weight and dispersity. Consequently, there is significant need for new polymeric biomaterials that are amenable to facile modification, multiple processing or manufacturing methods, and controlled degradation without the generation of a local acidic environment. With NSF funding, the PI (Grinstaff) and his team will design, synthesize, and evaluate of a novel class of natural metabolite-based, non-toxic, and biodegradable polymeric materials based on a polycarbonate of glycerol. The activities in this highly interdisciplinary and cutting-edge research environment will also afford educated and trained undergraduate and graduate students for employment in industry and academia.

 

Mark Grinstaff, Samsung

Basic Research on New Ionic Liquid Electrolytes: Synthesis

This basic science research project directed by Professor Grinstaff investigates his interest in new ionic liquids as potential electrolytes for Li ion batteries. Given his interest and past publications, Samsung has reached out to sponsor this project. Specifically, the Grinstaff laboratory will synthesize a small library of 10 new phosphonium and piperdium ionic liquids. We will mix these ionic liquids with differing Li salts and characterize the thermal properties, viscosity, conductivity, and electrochemical window of these electrolyte compositions.

 

Mark Grinstaff, MIT/Comm. Of Mass

Translation of a Hydrophilic Coating for Latex Condoms: The HydroGlide Coating

The HydroGlide Coating is a novel and stable hydrophilic coating on latex condoms that can maintain its lubricity when in contact with water. This technology will promote consistent and proper condom usage, while improving user satisfaction. The goal is to translate this novel latex coating technology to the market through collaboration with Biocoat Incorporated who will optimize this coating prototype towards one that is adaptable towards large-scale manufacturing under GMP.

 

Bjoern Reinhard, Millipore

Plasmonic Nanofilters For Viral trapping and inactivation

This award will go towards research into creating plasmonic metamaterials to develop a novel class of photonic filters that are capable of selectively trapping and inactivation of viruses. Several complementary technology developments, ranging from state-of-the-art electron-beam lithography, fabrication methods combined with simulation and design will be aimed at developing 21st century adaptive filters for biopharmaceutical applications. Evaluation of the Optical gradient forces in fabricated membranes will be combined with multi-physics modeling that include both plasmonics and hydrodynamics. Experiments on fluid feed materials and virus systems selected by EMD will be performed to characterize selective trapping. Data will be shared openly between BU and EMD, under NDA. An assessment of manufacturability, scalability will be performed in close consultation with engineers and scientists at EMD.

 

Bjoern Reinhard, BMC Corp.

Nanoplasmonic Metamaterial Filters

This project explores the mechanism underlying virus inactivation through laser irradiation.

 

Bjoern Reinhard, National Cancer Institute

Illuminating Dynamic Receptor Clustering in the Epidermal Growth Factor Receptor

Dysregulation of members of the epidermal growth factor (EGF) receptor (EGFR) family is associated with oncogenesis and tumor growth. Due to its relevance in cancer development, EGFR is an important target in cancer drug discovery, and several EGFR targeted therapies have already been developed. Their clinical success has, however, often been modest, reinforcing the need for a more complete understanding of the EGFR signaling pathway. This proposal focuses on the insufficiently understood role of large-scale EGFR associates (“clusters”) in signaling initiation and transduction, in particular. While it has long been known that ligand induced dimerization plays a critical role in receptor signaling, there is growing evidence that this textbook model needs to be augmented to account for the heterogenous lateral distribution of the receptor in the plasma membrane. The local enrichment of the receptors in ”micro-domains” or ”nanoclusters” could strongly affect cooperative receptor interactions and shift the local EGFR association equilibria through a local concentration effect. The experimental investigation of the fundamental mechanisms underlying the large-scale receptor organization with conventional fluorescence microscopy remains challenging, due to the method’s limitation with regard to throughput, spatial and temporal resolution, and maximum observation time. Plasmon Coupling Microscopy (PCM) is a novel non-fluorescence based approach that uses electromagnetic interactions between noble metal nanoparticles (NPs) to investigate receptor clustering on subdiffraction limit distances (but beyond the spatial barrier o Fluorescence Resonance Energy Transfer, FRET). NP’s do not blink or bleach, are very bright, and can be imaged in a conventional widefield microscope. Consequently, PCM facilitates the monitoring of EGFR clustering without limitations in observation time in many individual cells simultaneously. This competitive renewal builds upon the plasmon coupling based tools developed in the previous funding cycle and outlines a vigorous research plan to elucidate the structural origin of dynamic EGFR clustering. PCM will then be applied to test the hypothesis that receptor clustering regulates the mode and strength of signaling and to elucidate the mechanisms underlying a spatial regulation of signaling intensity and outcome. The obtained insight will improve the understanding of spatial regulation mechanisms for a broad range of receptors. Noble metal NPs are not only superb optical labels for characterizing EGFR clustering in the plasma membrane, but they also represent potential therapeutic tools to restore and enhance negative EGFR signaling after covalent attachment to EGF. This hypothesis is experimentally tested in this proposal. If successful, this strategy would provide a new approach for overcoming apoptosis evasion in cancer.

 

John Snyder & Linda Doerrer, National Science Foundation

Research For Undergraduates Program: Chemistry Research Addressing Biological Problems

This REU site will afford 30 undergraduates (10 per summer) the opportunity to engage in cutting edge, basic chemical research projects that address biological problems. REU students can choose from among 24 groups in BU’s Departments of Chemistry, Biology, or Biomedical Engineering. They will work in newly renovated laboratories, have access to the synthetic and computational resources of BU’s leading research centers, and be trained on state-of-the art instrumentation. The goal of the program is to provide undergraduates from 4-year colleges and community colleges who have limited or no research opportunities at their home institutions with an intensive, interdisciplinary research experience. At least 50% of the participants will be from community colleges with no research opportunities at their home campuses. The demographic aim is to have at least 70% of the students to be underrepresented minorities and at least 50% to be women. The program will also give preference to veterans applying from the target institutions. By fully integrating the REU students into the daily life of the laboratories and through mentoring by faculty, graduate students, and postdoctoral research associates, the REU students will fully experience the breadth of chemistry research and be motivated to pursue careers in science.

 

Mark Grinstaff, L-Oreal

Poly-amido-saccharide (PAS) Biomaterials for Cosmetic and Beauty Applications

This project will explore a new class of polysaccharides, recently reported, for their properties as new materials as well as their biological activity in anti-ageing and/or preservatives and/or photoprotection and/or depigmentation.

 

Aaron Beeler, National Science Foundation CAREER

Chemical Transformations Enabled by Flow Chemistry

This award funds specific projects that are integral to the long term development of the Beeler Research Group. The overarching objective of our research is synthesis of small molecules that are used as tools to study human diseases. To achieve these goals we have identified a number of reactions that are highly enabled by flow chemistry. The scientific projects outlined in this proposal will result in sigfnificant advances toward the synthesis of a number of important biologically active molecules. Furthermore, the projects will provide advancements in flow chemistry that will enable chemists in acadmia and industry to implement a number of challenging reactions. The education projects in the proposal will provide training for undergraduates in flow chemistry, which is emerging as a critical technology in industry. The outreach projects will provide high school students from a wide range of socioeconomic backgrounds with a foundational path toward STEM higher education and careers.   The first Aim is focused on expanding the utility of our flow photochemistry platform to develop reactions that will be highly useful in synthesis and medicinal chemistry. The second Aim is to develop a platform that is capable of milligram to multigram scale electrochemical reactions in flow. The third Aim will utilize highly reactive diazoalkanes in a Buchner reaction to access complex scaffolds. The proposal also outlines our continued involvement in outreach and education, including the Upward Bound program at Boston University to educate local high school students in chemistry, developing a summer camp for high school students, and integrating flow chemistry into the undergraduate laboratory curriculum.

 

Debbie Perlstein, National Science Foundation CAREER

Elucidating the role of ATP in cytosolic iron sulfur cluster biogenesis

Dr. Perlstein’s research focuses on how metals are mobilized and monitored within the cell so that they get to where they need to go and do not end up in places they shouldn’t. With this new five-year grant, Dr. Perlstein plans to unravel the molecular mechanism by which iron-sulfur cluster cofactors are assembled in the cytosol of eukaryotic organisms.  Since inhibition of this first step in cluster biosynthesis can lead to defects in DNA replication, DNA repair and protein synthesis, she expects this work will provide new insight into how cluster biogenesis affects these other fundamental biochemical pathways.

With the CAREER award, Perlstein also plans to develop new undergraduate course curriculum as well as building on current STEM outreach program efforts to begin training the next generation of scientists.

 

Mark Grinstaff, Brigham & Women’s

Efficacy and Safety of a Novel, Implantable Drug-Eluting Film in Sarcoma

Despite aggressive multimodality therapies combining surgery, radiation, and/or chemotherapy, mesothelioma is essentially a universally fatal cancer with the majority of patients succumbing to local recurrence. To date, there is no effective cure for this disease or means to prevent recurrence. Consequently, new approaches, biomaterials, and mechanisms to deliver pharmacologically active agents are needed. In the current proposal, we utilize a murine model of human mesothelioma to investigate a new approach to reduce intracavitary tumor recurrence with the delivery of chemotherapy via unique tumor localizing polymeric nanoparticles (NPs) administrated locally at the time of surgical resection. The particle localizes to tumor in situ where upon endocytosis these “expansile” nanoparticles (eNPs) undergo a pH dependent transformation and swell from 100 nm to 1000 nm in diameter thus releasing the encapsulated chemotherapeutic agent intracellularly and acting as a drug depot, or reservoir, to deliver high local drug concentrations. Uniquely, expansion of eNPs also results in a functional depot whereby subsequently delivered intracavitary chemotherapy is concentrated inside eNP with prolonged delivery in situ at the sites of tumor where eNP accumulate. This is in contrast to conventional polymer delivery systems that degrade (e.g., poly(lactic-co-glycolic acid) particles), and result in burst release of their drug payload. We hypothesize that these eNPs will, via this unique mechanism, afford a higher intracellular concentration of paclitaxel (Pax), with greater efficacy in the prevention of local recurrence of mesothelioma after surgery that is superior to standard resection or Pax alone without adversely affecting healing at the surgical site. Importantly, we have data demonstrating that eNPs are readily internalized by cancer cells, act as a drug depot, and are superior to the standard Pax-Cremaphor formulation in preventing microscopic malignant disease in vivo.

 

Mark Grinstaff, NIH
Dissolvable Hydrogel Dressing for the Treatment of Burns

This will study the synthesis, characterization, and evaluation of a hydrogel dressing that dissolves and can be easily removed from the wound surface of a patient with second degree burns with no further trauma. Burns are one of the most common and devastating forms of trauma. Each year, more than 300,000 people die from fire-related burn injuries and millions suffer from burn-related disabilities and disfigurements with psychological, social, and economic effects on both the survivors and their families. Dressing removal is reported to be the time of most pain (after the burn itself) and opioids continue to be the mainstay of treatment for the burn patient. The duration of a burn dressing change in a typical injury requiring ICU/OR level care is often at least 60 minutes with induction of general anesthesia, which can extend to more than three hours depending on the case. At present, all clinically approved available dressings adhere to the wound surface so that each change of dressing leads to traumatization of newly formed tissues on the outer layer of the body’s surface, delayed healing, and great personal suffering for the injured patient. The proposal describes a thiol terminated dendron and a bifunctional NHS-activated PEG that react with each other to form a thiolester linked hydrogel dressing that can be subsequently dissolved by exposure of an aqueous thiol solution via a thiol-thiolester exchange mechanism. These experiments will test the hypothesis that a hydrogel-based, dissolvable burn dressing will provide a barrier to infection, promote wound healing, and be easily removable on demand. Importantly, it presents preliminary data demonstrating the synthesis, characterization, and performance of a dissolvable hydrogel dressing prototype.

 

Sean Elliot, Department of Energy

Tuning directionality for CO2 reduction in the oxo-acid:ferredoxin superfamily

Exploiting catalytic chemistry for bioenergy production requires a detailed understanding of the molecular mechanisms of multi-electron redox processes, particularly those that transform/capture CO2. Understanding the molecular details of these complex reactions is a major challenge in modern energy science, particularly in the context of CO2 transformations, and the way in which bacteria and archaea capture CO2 for biomass. Here, we have focused on the remarkable catalysts used by nature to achieve either the oxidative liberation of CO2, or its formal reduction (and capture) in the form of useful intermediaries en route to biomass.

The enzymes that achieve CO2 reductions are highly powerful catalysts; yet very little is known about how they work, nor how they can be tuned to favor CO2 reduction chemistry. Through the completion of the project, this knowledge gap will be addressed in the context of the enzymatic chemistry of the oxo-acid:ferredoxin oxidoreductase (OFOR) superfamily, which is capable of CO2 reduction. We believe that our studies of the OFOR superfamily will reveal the molecular details of how nature biases the reactivity of an enzyme to preferentially reduce CO2. These efforts will yield foundational knowledge that will be broadly applicable to marrying the thermodynamics of redox reactions to atomistic information of enzymatic mechanism. We will examine a series of OFOR enzymes through three Aims over a 3-year period.

 

Collaborative Research Discovers New Approach in the Treatment of Liver Cancer

April 9th, 2012 in CMLD, Publications, Research, Schaus, Scott

Prof Scott Schaus

Professor Scott Schaus

Until now, there has been no effective, systemic treatment for liver cancer (hepatocellular carcinoma), the fifth most common cancer worldwide. Writing in the Proceedings of the National Academy of Science (PNAS), Professor Scott Schaus (Chemistry) and Professor Ulla Hansen (Biology and Molecular Biology, Cell Biology & Biochemistry) have reported their discovery of a new protein target for chemotherapy in the treatment of liver cancer — the transcription factor LSF. LSF occurs at high levels in the tumor tissue of patients with liver cancer and is known to promote the development of cancer (oncogenesis) in studies using laboratory rodents.

The co-investigators have identified small molecules that effectively inhibit LSF cellular activity, which in turn slows the growth of the cancer. In particular, they found that one such molecule, Factor Quinolinone Inhibitor 1 (FQI1), derived from a lead compound, inhibits the ability of LSF to bind DNA both in extracts (in vitro, as determined by electrophoretic mobility shift assays) and in cells. Consistent with inhibiting LSF activity, FQI1 also eliminates the ability of LSF to turn up transcription. While FQI1 quickly causes cell death in LSF-overexpressing cells, including liver cancer cells, healthy cells are unaffected by the treatment. This phenomenon has been called oncogene addiction, where tumor cells are “addicted” to the activity of an oncogenic factor for their survival, but normal cells can do without it. This characteristic is very encouraging for use
of such compounds clinically.

Structures of LSF inhibitors

Structures of LSF inhibitors

Following in vitro trials, the researchers tested the efficacy of FQI1 in inhibiting liver cancer tumor growth by injecting HCC cell lines into rodent models. FQI1 was observed to significantly inhibit tumor growth with no observable side effects (general tissue cytotoxicity). These dramatic findings support the further development of LSF inhibitors as a promising new chemotherapy treatment for liver cancer.

This work is featured as part of the series, “BU Takes on Cancer,” in BU Today (April 11, 2012).

 

Citation: T.J. Grant, J. A. Bishop, L.M. Christadore, G. Barot, H.G. Chin, S. Woodson, J. Kavouris, A. Siddiq, R. Gedler, X-N. Shen, J. Sherman, T. Meehan, K. Fitzgerald, S. Pradhan, L.A. Briggs, W.H. Andrews, D. Sarkar, S.E. Schaus, and U. Hansen, “Antiproliferative small-molecule inhibitors of transcription factor LSF reveal oncogene addiction to LSF in hepatocellular carcinoma,” Proc. Natl. Acad. Sci. U.S.A., March 20, 2012, Vol. 109, No. 12, 4503-4508.

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Renovation Inspires Technology Innovation in Undergrad Organic Lab

March 16th, 2012 in Alumni, Front Page, PFF, Schaus, Scott, Snyder, John, Students, Teaching, Undergraduate

Undergraduate Organic Lab

BU Chemistry has dramatically improved the undergraduate organic chemistry laboratory by giving students access to major research instrumentation and state-of-the-art technology. By enabling more modern experimentation, these resources foster critical thinking and problem solving skills that prepare undergraduates for  graduate and pre-professional schools or for careers in industry. Advanced experimentation also enables more sophisticated student-designed research-type projects.


Undergraduate Organic Lab Undergraduate Organic Lab

Renovations and instrumentation

Renovations in the Metcalf Center for Science and Engineering (Summer 2011) have transformed our organic chemistry instructional laboratories into an 6,350 sq. ft. suite with fume hoods and bench areas for each student, auxiliary support space, and a chemical stockroom. Space has been dedicated for an undergraduate instrumentation center for with fully automated high field nuclear magnetic resonance (NMR), ultra-performance liquid chromatography–mass spectrometry (UPLC-MS), Fourier transform infrared spectroscopy (FT-IR), and gas chromatography-mass spectrometry (GC-MS). Microwave reactors allow for rapid reaction rates, enabling multistep syntheses to be undertaken in a single day.

Undergraduate Organic Lab Undergraduate Organic Lab

Advanced Technology in the Laboratory Curriculum

The entire laboratory curriculum of our sophomore-level organic chemistry sequence has been transformed with the adoption of the “paperless laboratory” through the use of electronic laboratory notebooks. Spearheaded by Professor John Snyder and Professor Scott Schaus and Postdoctoral Faculty Fellow, Seann Mulcahy, integration of these technology resources have enabled the creation of an open-access repository of laboratory protocols, design of laboratory experiments that facilitate sharing of data between students and between disciplines, exposure to automated NMR, GC-MS, and UPLC-MS, and remote download and manipulation of spectroscopic data.

  • Undergraduate Organic LabFast Forward to the 21st Century -The new instrumentation advances undergraduate capabilities well beyond those in traditional sophomore organic textbooks that repeat traditional experiments. Instead, we have designed novel, research-oriented, exploratory experiments that have applicability to modern organic chemistry. These include cross-coupling experiments, olefin metathesis, and many others. Experiment protocols are available on BU’s Digital Common site (DCommon), an open-access online repository that is accessible not only by our students, but by outside instructors as well. Users can be granted upload privileges to deposit modified or new protocols thereby creating a rich resource to the worldwide research community. In addition, a DCommon collection of NMR and UPLC-MS spectra is being compiled as a teaching tool for organic chemistry courses.

Undergraduate Organic Lab

  • Major Instrumentation – BU is unique in using the latest instrumentation for routine, hands-on training at the sophomore level. The laboratory’s state-of-the-art instrumentation also allows comprehensive characterization of synthetic material prepared in each experiment. Students now routinely run 1H and 13C NMR (and 2D COSY), UPLC/MS, GC/MS, and FT-IR on their own samples and to obtain a set of data which approaches the quality needed for publication.

 

Undergraduate Organic Lab

  • Into the Cloud – Our students are now using fully electronic laboratory notebooks, which they populate  on their laptops with reaction details, procedural notes, and safety protocols. Analytic data and spectra (manipulated and interpreted remotely) are uploaded into the notebook and serve as part of their final laboratory reports.

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High School Researcher in Schaus Lab Wins SIEMENS Award

February 21st, 2012 in Faculty, Front Page, Schaus, Scott, Students

Joshua Kubiak

Joshua Kubiak

The Research Internship in Science & Engineering Program (RISE) provides academically motivated high school seniors the opportunity to conduct university-level research in state-of-the-art laboratories.

In the summer of 2011, Joshua Kubiak, a senior from the Louisiana School for Math, Science and the Arts (Natchitoches, LA), joined the laboratory of Professor Scott Schaus to conduct research for 3 months on Asymmetric Conjugate Addition of Ortho-Quinone Methides as a Pathway to Communesin Analogs.

Professor Scott Schaus

Professor Scott Schaus

Under the mentorship of Professor Schaus and graduate student, Yi Luan, Joshua made a molecular scaffold which can then be built upon to create chemical compounds with potential medicinal applications. The quality of his research has been recognized by a Siemens Foundation Award.

Joshua is the first student from his school to be named a Regional Finalist in the Siemens Competition, and he plans to pursue a career in drug design and development.

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Schaus & Virus Research Featured in ScienceDaily

January 18th, 2012 in CMLD, Front Page, Research, Schaus, Scott

Professor Scott Schaus

Professor Scott Schaus

ScienceDaily, has featured the research of a team of Boston University scientists in which they identified a novel compound that inhibits viruses from replicating.

The findings, which were published online in the Journal of Virology, could lead to the development of highly targeted compounds to block the replication of poxviruses, such as the emerging infectious disease, Monkeypox.

Investigators from the Boston University School of Medicine (Dr. Ken Dower and Dr. John Connors) teamed with Professor Scott Schaus to use a library of chemicals from the CMLD-BU to identify compounds that could stop vaccinia from replicating inside human cells.

Professor Schaus is Associate Professor in the Boston University Department of Chemistry. The Center for Chemical Methodology and Library Development at Boston University (CMLD-BU) is an National Institutes of Health Funded Center of Excellence in the area of chemical methodology and library development.

Read the ScienceDaily article at:

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Drug Mechanism of Action Using Bioinformatic Pathway Analysis

August 3rd, 2011 in Faculty, Front Page, Graduate, Publications, Research, Schaus, Scott, Students

Lisa Christadore

Lisa Christadore

Professor Scott Schaus

Professor Scott Schaus

Professor Scott Schaus and Graduate Student Lisa Christadore are co-authors of:

Network-based prediction for sources of transcriptional dysregulation using latent pathway identification analysis

Published in PNAS in July 2011, the paper represents their collaborative work with researchers in the BU Department of Mathematics and Statistics, Professor Eric Kolaczyk and Graduate Student Lisa Pham.

It reports on the effectiveness of their novel method, latent pathway identification analysis (LPIA), in providing insights into systemic biological pathways and key cellular mechanisms that dictate disease states, drug response, and altered cellular function. The work was supported by NIH, NSF, and DOD.

Network-based prediction for sources of transcriptional dysregulation using latent pathway identification analysis.

Schematic illustration of the proposed LPIA method.

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BU Postdoctoral Researcher Awarded Humboldt Fellowship

February 3rd, 2011 in Front Page, Graduate, Schaus, Scott, Students

Dr. Philip Moquist

Dr. Philip Moquist

Dr. Philip Moquist has received a postdoctoral research fellowship from the Alexander von Humboldt Foundation to study in Germany with Professor Gerhard Erker at the Westfaelische Wilhelms-Universitaet Muenster Organisch-Chemisches Institut in Muenster.

His research proposal is to work on the asymmetric activation of hydrogen using electron deficient boron complexes. The Humboldt Foundation aims to promote academic cooperation between German scientists and researchers from other countries.

Dr. Moquist received his B.S. in Chemistry at the University of California, San Diego. In 2010, he recieved his Ph.D. in Chemistry under the guidance of Professor Scott Schaus at Boston University. His work at BU included the development of enantioselective boronate reactions.

Due to the large number of e-mails that Dr. Moquist has received, we request that you do NOT contact Dr. Moquist for assistance in applying for the Fellowship.

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NIGMS Renews Funding for the CMLD-BU

October 1st, 2008 in CMLD, NIH, Panek, James, Porco, John, Schaus, Scott, Smith, Kevin, Snyder, John, Stephenson, Corey

The National Institute of General Medical Sciences (NIGMS) is continuing its support of the CMLD-BU as one of five Centers of Excellence addressing the problem of how to develop small molecule libraries and techniques for making them that meet all the needs of pharmaceutical and biomedical scientists.

The CMLD-BU was originally established in 2002. The renewal is for another 5 years (through 2013) and is worth more than $11.5 million. The first year’s funding, $2.6 million, will be used to develop microfluidics and other strategies to synthesize small molecules for application by the biological community. The program is highly collaborative. Professor John A. Porco, Jr., who is the Director and Principal Investigator, is joined by Co-PI’s Professors Jim Panek, Scott Schaus, John Snyder, and Corey Stephenson, who are leaders in the field of organic chemistry.

The goal of the Center is to develop cutting-edge technologies to generate, analyze, and optimize chemical libraries and synthesize thousands of novel chemical entities using high-throughput techniques. It is also making these methods and libraries broadly available for biomedical research and drug discovery. The CMLD’s PI’s are collaborating with biologist, Professor Tom Gilmore, to determine the physiological activities of new molecules.

Schaus Group Develops New Asymmetric Route To α-Amino Acid Esters

June 7th, 2008 in Faculty, Publications, Research, Schaus, Scott

Chemical & Engineering News: Science & Technology (5/19/08) reports in a “Highlight” that Sha Lou and Scott E. Schaus have developed the first asymmetric catalytic version of the reaction.

It uses chiral biphenol catalysts to convert alkenyl boronates, secondary amines, and glyoxylates to chiral α-amino acid esters with good yields and high enantiomeric ratios (J. Am. Chem. Soc., DOI: 10.1021/ja8018934). The advance eliminates the need for stoichiometric chiral starting materials and opens the way to a broader range of products.

The work was done through the NIN-funded Boston University Chemical Methodology and Library Development Center

Asymmetric Petasis Reactions Catalyzed by Chiral Biphenols

Asymmetric Petasis Reactions Catalyzed by Chiral Biphenols

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CMLD-BU Scientists Awarded National Institutes of Health Grant in Pilot-Scale Libraries for High-Throughput Screening Program

December 15th, 2005 in CMLD, Faculty, Panek, James, Porco, John, Schaus, Scott, Snyder, John

Co-investigators of the Boston University Chemical Methodology and Library Development Center (CMLD-BU) (http://cmld.bu.edu) have been awarded a three-year grant for their joint proposal “Generation of Stereochemically and Structurally Complex Chemical Libraries.” The goal of the work by Professors Porco, and co-Principal Investigators Panek, Schaus, and Snyder, is to generate a number of stereochemically and structurally complex chemical libraries for inclusion in the National Institutes of Health (NIH) Molecular Repository (http://mlsmr.glpg.com/MLSMR_HomePage/index.html). They will develop five library projects that are distinct from ongoing and planned CMLD-BU library projects, but which utilize novel chemistries previously developed in their laboratories. Target pilot libraries include complex dihydropyrimidones, azaphilone-derived libraries, tetracyclic alkaloid-type libraries, exo-methylene scaffolds and derived spirocycles, and macrocyclic lactams. In addition, all planned libraries have been designed to include unique structures that do not overlap in chemical space with molecules currently in the PubChem database. Data will be shared using an internet-based structure-searchable database of synthesis protocols.

The Molecular Libraries and Imaging Initiative is a component of the “New Pathways to Discovery” theme of the NIH Roadmap, which seeks to enable the rapid transformation of new scientific knowledge into tangible benefits for public health. While high-throughput screening (HTS) of small-molecule libraries is widespread in the pharmaceutical industry, the goal of the Molecular Libraries (ML) Roadmap Initiative is to facilitate the use of HTS and chemical libraries within the academic community. It is anticipated that the ML initiative will produce research tools (including novel small-molecule modulators of cellular function and phenotypic assays) to facilitate studies of biology and physiology (http://nihroadmap.nih.gov/molecularlibraries). It is anticipated that the initiative will complement private sector drug development efforts by contributing to the identification and validation of novel drug targets, as well as molecular structure classes with potential for development into therapeutics. The initiative promises benefits to public health, especially for rare or marginalized disorders.

John PorcoProfessor James PanekScott SchausProfessor John Snyder