Tagged: 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.
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.
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.
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.
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.
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.
- Fast 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.
- 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.
- 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.
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.
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.
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:
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.
Professor Scott E. Schaus (Organic Chemistry) joined our faculty in Fall 2001. Scott received his B.A. in Chemistry, summa cum laude from Boston University in 1995 and a Ph.D. in Organic Chemistry with Eric Jacobsen at Harvard University in 1999.
In the Jacobsen laboratory, Scott worked on the development of asymmetric catalytic reactions for the synthesis of complex natural products. As a postdoctoral student in Andrew Myers’ laboratory at Harvard University (1999-2001), in collaboration with the Center for Genomics Research at Harvard University, Scott utilized genome-wide transcriptional profiling to investigate the mechanism of drugs in living cells.