In response to BU’s continued success in recruiting faculty who are addressing today’s most challenging research problems, the Chemical Instrumentation Center (CIC) on the Charles River Campus is successfully growing its infrastructure with support from the National Science Foundation (NSF), the University, and industry.
In September 2013, the Chemistry Department and the CIC received support from the NSF, with cost-sharing by BU, to purchase a MALDI-TOF Mass Spectrometer. This instrument will enable the work of faculty, postdoctoral researchers, graduate students, and undergraduates in Chemistry, Biology, Biomedical Engineering and other departments of the Charles River Campus. It will help advance chemical research in the life processes, including such areas as dendritic and linear polymers, proteins and peptides, and novel synthetic organic materials. It addition, the MALDI-TOF will enable truly interdisciplinary training at the interface of Chemistry-Biology, Polymers, and Organic Materials.
With support from the University, Chemistry has also recently (January 2014) purchased a 300 MHz Nuclear Magnetic Resonance (NMR) Spectrometer to replace an obsolete system. The new high resolution FT NMR will facilitate the access and development of more sophisticated experiments in undergraduate courses. The Chemistry Department provides hands-on training to more than 1,500 undergraduate students on NMR, LC/MS and other advanced analytical characterization techniques on a yearly basis. In conjunction with the LC/MS, supported by the University in 2011, the new 300 MHz NMR will continue BU’s efforts to prepare its undergraduates with the modern instrumentation skills necessary for their graduate and/or industry careers.
Most recently, in February 2014, the CIC was the recipient of a major instrument donation (mass spectrometer) from the biotechnology community. The instrument, a Fourier Transform Ion Cyclotron Resonance (LTQ-FT-ICR) MassSpectrometer will advance studies on advanced proteomics and metabolomics. It will immediately impact the research programs of faculty across several departments of CAS and ENG, as well as at the BU Medical School and cognate colleges (Wellesley and Simmons). This donated instrument is only the most recent from private industry. Past donations have included other mass spectrometers and liquid chromatography instrumentation.
The CIC, which was redesigned in 2005, is located in the lower level of the Metcalf Science Complex (SCI) with satellite space in the Life Sciences & Engineering Building (LSE). Under the leadership of its Director, Dr. Norman Lee, the Center has grown to become a core resource supporting research and teaching activities on the CRC and the BU Medical Campus. It houses four major areas of analytical and optical instrumentation, including chromatography and mass spectrometry (GC-MS, HPLC, LC/MS), magnetic resonance spectroscopy (EPR, NMR), optical & analytical spectroscopy (FT-IR, Fluorescence, UV-Vis, etc) and x-ray crystallography. For further information about the Center, please visit the Center’s website.
Fourth-year graduate student Thomas Sisto in Prof. Ramesh Jasti’s group has been awarded the 2013-2014 AstraZeneca Fellowship in Organic Chemistry. The award is in recognition of his scientific creativity and productivity.
Tom joined the Jasti research group as a Dean’s Fellow in the Summer of 2010. Since then he has published four papers (three as a first author). Currently Tom’s research aim is to synthesize a carbon nanotube by organic synthesis. Achieving this goal will be an enormous accomplishment for organic chemistry, as well as for materials science. At the same time, he has developed a collaborative project with Prof. Colin Nuckolls‘ group at Columbia University to use cycloparaphenylenes as “seeds” to “grow” uniform carbon nanotubes by traditional chemical deposition methods. The types of nanotubes that would be produced in this proces
s would be of the armchair variety, which has 1000-fold conductivity relative to copper and would be a major achievement. AstraZeneca is a global innovation-driven biopharmaceutical company specializing in the discovery, development, manufacturing, and marketing of prescription medicines healthcare.
MIT Whitehead Institute senior scientist, Dr. Luke Whitesell, and Boston University’s Prof. John Porco, Director of the CMLD-BU, have received a 3-year award from the NIH entitled “Inhibiting the Heat Shock Factor 1 (HSF1)-regulated transcriptional program in cancers.” This combined biology/chemistry team aims to identify highly potent and selective HSF-1 inhibitor probes with useful activity in vivo. These inhibitors will serve as promising leads for the rapid development of useful anticancer drugs with a completely new mode of action. Luke Whitesell is a pediatric oncologist whose research in the laboratory of Prof. Susan Lindquist is focused on cellular heat shock response (HSR) and heat shock proteins, a class of molecules that guides other proteins to fold correctly. HSF1 is the master regulator of the HSR maintaining protein homeostasis during times of proteotoxic stress. It functions as a transcription factor, binding to and coordinating the expression of numerous genes, in effect, acting as a “transcriptional program.” This program can vary depending on the particular cell and stress type.
While Dr. Whitesell and his colleagues have shown that HSF1 is co-opted by tumor cells to promote their own survival at the expense of their hosts, they do not know how the HSF1 coordinates during malignancy, how it might relate to a classic HSR, and whether it impacts human cancer. They have turned to the Porco laboratory for its expertise in the synthesis of complex natural products and derivatives, as well as library synthesis and medicinal chemistry. The Lindquist laboratory’s ~300,000 compound high throughput screen for inhibitors of HSF1 identified the natural product, rocaglamide. In this work, John Porco and his group will optimize the HSF1 inhibitory activity of the rocaglate scaffold; optimize the scaffold’s pharmacological properties; and evaluate the antitumor activity of rocagalate analogs in mouse models of cancer.
The Porco laboratory’s unique photocycloaddition methodology developed for the synthesis of various targets is the basis of the medicinal chemistry efforts in the current award to optimize these compounds as HSF-1 inhibitors.
The work of 22 students was spotlighted in this year’s day-long Undergraduate Research Symposium (URS). The record number and outstanding quality of the projects presented underscored the importance of the hands-on, challenging research that is the hallmark of BU’s Chemistry major. The even was organized by the Undergraduate Programs Committee with laudable efforts from Mr. Moneil Abu Speitan (the department’s undergraduate administrator). The URS was first instituted in 1987 by then Director of Undergraduate Studies, and now Emeritus, Prof. Mort Hoffman, and has been a much anticipated, spring’s-end annual event ever since. The Symposium is modeled along the lines of talks at an American Chemical Society (ACS) meeting: 12 minutes of presentation followed by 3 minutes of questions and discussion. Capping the day was the announcement of the Departmental Awards, followed by a celebratory BBQ for the students, their faculty advisers, graduate mentors, and their guests. To view URS photos, please click here.
The American Association of University Women (AAUW) has awarded Liz Hirst, a fifth year graduate student in the Jasti Group, with a year-long American Fellowship that will enable her to complete her dissertation research in the next year.
Hirst’s research is highly interdisciplinary, combining chemistry, physics, and materials science. The focus of her work is the synthesis of novel cycloparaphenylenes (CPPs) with nitrogen incorporated into the backbone. CPPs represent the smallest unit cell of a metallic carbon nanotube (CNT). Also termed carbon nanohoops, CPPs consist of all para linked benzene rings. Nitrogen-doped CPP synthesis will enable a fundamental exploration of the structure-property effects of adding nitrogen to carbon networks. This could serve as an empirical model system for understanding the electronic changes in nitrogen-doped graphitic materials. It will also allow for correlation of theoretical predictions to reality. This synthesis will also enable construction of novel carbon-based materials. Specifically, once the target CPPs are synthesized, Liz will explore incorporation of these molecules into 3-d porous carbon-based frameworks. These frameworks may have uses in energy storage and small molecule detection.
In addition to pursuing her research, Liz Hirst works to promote the representation of women in the sciences. She has played a leadership role in the BU Women in Chemistry, currently serving as the organization’s president. A hallmark of her presidency has been outreach to local area high schools and the Girl Scouts to enable students to participate in and experience chemistry research.
Benjy Cooper, a second-year Chemistry graduate student in the Grinstaff Group, has been awarded a National Science Foundation Graduate Research Fellowship. These awards are highly competitive: in 2013, the NSF chose only 2,000 fellows from among 13,000 applicants. Fellows share in the prestige and opportunities that become available when they are selected and receive a three-year annual stipend. At the same time, there is the high expectation that Fellows will become knowledge experts who can contribute significantly to research, teaching, and innovations in science and engineering.
Benjy’s research project for his fellowship is the “Development of Dendritic Macromolecules for Increasing Boundary Lubrication.” In addition to Prof. Mark Grinstaff, he will be advised by Dr. Brian Snyder, Associate Professor of Orthopedic Surgery at Children’s Hospital Boston. The project aims to synthesize and characterize a series of dendritic macromolecules that enhance boundary lubrication of cartilaginous surfaces, and to evaluate the dendritic network’s efficacy in reducing friction and wear.
At the same time, in terms of broader impact, Benjy will mentor underrepresented high school students performing summer research in the Grinstaff lab, and he plans to network with the non-scientific community to present his research to a broader, more general audience (e.g. through public seminars at the Boston Museum of Science).
Prof. Ramesh Jasti has received a Boston University Ignition Award to investigate carbon nanohoops as advanced energy storage materials. The winning proposal was developed in collaboration with 2nd year graduate student, Evan Darzi, in the Jasti Group. Through this award, they aim to advance their research to commercialization, possibly as a start-up company.
Porous carbon nanostructures have shown great promise as energy storage materials for high performance batteries and capacitors. However, current production processes are very crude and result in structurally ill-defined and heterogeneous materials. The Jasti Group has developed the synthesis of the smallest possible slice of a carbon nanotube (termed “carbon nanohoops”), with various diameters and complete uniformity. Importantly, these structures self-assemble in the solid-state to generate tubular materials that have long-range ordered channels, reminiscent of a carbon nanotube. This configuration renders them ideal as potential carbon energy storage materials, with other possible long-range applications in hydrogen storage, CO2 sequestration, and nanofiltration. In this award, the Jasti Group will explore the effect the hoop diameter and crystallinity have on charge capacitance, discharge rates, and energy storage systems. At the same time, they will develop a “flow” system for continuous synthesis of these carbon nanohoops. The work will test the hypothesis that these materials will outperform currently available porous carbon materials, as well as commercially utilized capacitors and batteries. These technical advances would enable large-scale production of carbon nanohoops and position the technology as commercially attractive for batteries and capacitors.
Boston University’s competitive Ignition Award Program funds faculty to advance their research toward commercialization (e.g., licensing, startup companies). Prof. Scott Schaus and his co-inventor, Prof. Ula Hansen in BU Biology, have received an Ignition Award to develop a small molecule chemotherapeutic for the effective treatment of primary liver cancer.
Liver cancer, hepatocellular carcinoma (HCC), is the fifth most common cancer worldwide (approximately 1 million new cases each year) and the third largest cause of deaths (600,000 deaths each year). Due to metabolic syndrome and hepatitis, the incidence of liver cancer is increasing and there are few therapeutic options. Currently there is only one FDA-approved drug (Nexavar) that can enhance lifespan by only 3 months, with significant negative side effects.
The BU research team has shown that transcription factor Late SV40 (LSF) is an oncogene for HCC, highly expressed in patient tumors, driving both tumor growth and metastasis. Their work has demonstrated that LSF inhibitors cause rapid death of HCC cells in vitro and that these inhibitors stop HCC growth in vivo (mouse models). There is a remarkable lack of side effects/toxicity in the mouse models. With the Ignition Award, they will perform a detailed toxicological assessment of compounds; assess the pharmacokinetic and oral availability; and determine the LSF biological targets that lead to cell death in HCC upon treatment with inhibitors. Through licensing, they anticipate that they will be able to develop new small molecule LSF inhibitors and a biomarker for early stage disease.
The Alfred P. Sloan Foundation has selected 126 outstanding U.S. and Canadian scientists to receive Sloan Research Fellowships in 2013. The President of the Foundation, Dr. Paul Joskow, considers these Fellows, “the best of the best among young scientists.” Among this year’s recipients is Prof. Ramesh Jasti whose work firmly places him in this group.
A central goal of Prof. Jasti’s research is to develop new organic synthesis methods to prepare carbon nanomaterials with high levels of homogeneity. Currently, carbon nanomaterials (e.g. carbon nanotubes and graphene) are prepared by methods that only provide mixtures with varying properties. A significant challenge in nanoscience is to develop syntheses for the preparation of homogenous batches of carbon nanotubes with a predetermined structure/property on demand.
Ramesh has excelled in the production and characterization of carbon nanotube “monomers.” In just three years, he has established himself as the world leader in this area being only one of three individuals capable of producing carbon nanohoop structures. What distinguishes his approach is that is it is highly amenable to production scale quantities and is also size-selective. He has been able to achieve the synthesis of more than gram quantities in single batch production. In the characterization of the nanotube monomers, he has also demonstrated the size-dependent optoelectronic properties of these structures and that some of these monomers organize into carbon nanotube‐like structures in the solid state. His working is leading the way to helping to realize the full potential of these materials in electronics, energy, and sensors applications.
Prof. Jasti joined the Department of Chemistry in Fall 2009 as an Assistant Professor. He carried out his doctoral studies at the University of California, Irvine, in the laboratory of Professor Scott Rychnovsky (2006). Upon completion of his doctoral studies, Ramesh was a Postdoctoral Fellow at the Molecular Foundry at the Lawrence Berkeley National Laboratory, where he began pursuing the bottom-up organic synthesis of carbon nanotubes in the laboratory of Carolyn R. Bertozzi, the Foundry’s Director.
The National Institutes of Health Exploratory/Developmental Research Grant Program (R21) funding mechanism is intended to encourage high risk but potentially high impact research. Prof. Karen Allen and her collaborator at the University of New Mexico, Prof. Deborah Dunaway-Mariano, have received a two-year R21 award to understand the structure and function of trehalose-6-phosphate phosphatase (T6PP), an enzyme identified in screens of C. elegans as a potential therapeutic target for infectious diseases caused by parasitic nematodes: lymphatic filariasis.
Lymphatic filariasis, commonly known as elephantiasis, is a mosquito-transmitted disease. Disfiguring and debilitating, it is endemic to 81 countries and affects 120 million people. A “neglected tropical disease,” there are currently very few medicines available to treat these infections and resistance to current approaches is emerging. This work will develop a greater understanding of T6PP structure and function, with an eye toward drug development. Profs. Allen and Dunaway-Mariano and their groups aim to capture multiple conformational states of the enzyme to develop a highly detailed analysis of the enzyme’s chemistry and possible regions to target by small molecule inhibitors. Furthermore, they will design and test inhibitors of the T6PP. The work is very likely to yield valuable information regarding the function and inhibition of an enzyme family that is currently under-examined as a therapeutic target.