Can a molecule be beautiful?
As director of BU’s Center for Molecular Discovery (CMD), John Porco has helped to create some 7,000 new molecules. To a chemist’s eye, their ornate “architecture” makes them beautiful, says Porco. But to the millions of people with conditions like Alzheimer’s disease, cancer, and infections that don’t respond to existing therapies, these molecules have beauty of a very different kind: they just might be able to treat diseases that today’s drugs can’t cure.
The molecules in the CMD’s boutique library are far more complex than those you’d find in standard, off-the-shelf compounds. That makes them more like the biologically active molecules found in nature, and more likely to deliver precision treatments that aren’t toxic to healthy cells. But it also makes them challenging to synthesize. In fact, drug makers traditionally prefer to use simple molecules because they are easier to create in the lab.
“When you’re running the same reaction dozens or hundreds of times, you want it to work every time, so people generally use very simple reactions, which generally give rise to very simple molecules,” explains Lauren Brown, research assistant professor of chemistry and assistant director of the CMD. “The more complex a molecule is, the more difficult it is to put together.”
Associate Professor Debbie Perlstein is going to sunny Ventura, CA next week to present at the week long Metals in Biology Gordon Research Conference. Her talk, which she will give on Tuesday evening, is titled “Piecing Together Apo-Target Recognition in Cytosolic Iron Sulfur Cluster Biosynthesis.” For more information about Dr. Perlstein and her research please visit: Perlstein Faculty Page
The Department of Chemistry regrets to announce the passing of our dear colleague, Mr. Mertin Betts, on October 18, 2015.
When Marty joined Chemistry in 2004, he had already enjoyed a successful professional career, and his interest in the laboratory supervisor position was motivated by his enthusiasm for chemistry and education. The members of the Department who interviewed Marty were immediately impressed by his friendly manner, a quality that made him a favorite with his work-study students, most of whom returned to work for him year after year until they graduated.
Marty’s dedication to the Department and his students was remarkable and thorough: he kept his labs organized and running smoothly, which was no small accomplishment given the hundreds of students who passed through them each semester. Faculty members and teaching fellows relied upon him to ensure that everything worked, and it did. Moreover, Marty took the safety of the students in his labs to heart, and he would remind them in a friendly but firm manner of the need to work safely and with the right equipment. He didn’t hesitate to remind staff and faculty either…and some of us occasionally needed that reminder.
What made Marty such an important part of Chemistry, however, was not just his professional competence and his passion for education, but his openness to his colleagues. He was funny, warm, a family man, and a gentleman. For eleven years, he was an important and beloved part of Chemistry, a man who, whether they realized it or not, contributed to the futures of thousands of students, and enriched the lives of all those fortunate enough to work with him.
We miss him.
To Marty’s family and his friends outside of Chemistry: thank you for sharing Marty with us. We share your grief, but also rejoice that we had the good fortune to know him. He was an educator, a colleague, and a friend, and he certainly made the Department a better place by being a part of it.
Three undergraduate students from the early 1970’s met their research advisor, Professor Emeritus Morton Z. Hoffman, and his wife, Sandy, recently for dinner at the Post 390 restaurant in Boston. The students were co-authors with him on a publication, “Generation of Radicals in the Charge-Transfer Photochemistry of Coordination Complexes of Cobalt(III) in Aqueous Solution,” J. Phys. Chem., 78, 686-691 (1974).
Deborah (Campano) German (CAS ‘72) was also a student in Hoffman’s CH101-102 lecture section in 1968-69. She received an M.D. degree from Harvard University and is now Dean of the College of Medicine and Vice President for Medical Affairs of the University of Central Florida in Orlando. She was married to fellow chemistry alumnus, Larry German (CAS ‘72), who passed away some time ago.
Evan (Rick) Kantrowitz (CAS ‘71), who took CH111-112 with Professor John Endicott in 1967-68, just retired as Professor Emeritus after a 37-year career in the Department of Chemistry of Boston College. He received a Ph.D. from Harvard University with Bill Lipscomb as his research supervisor. His wife, Ellen, accompanied him.
Marc Weinberg (CAS ‘74, MED ‘77) was also in Hoffman’s CH101-102 class in 1970-71. He is President of Marc Weinberg M.D. Personal Healthcare, Ltd. in Providence, Clinical Professor of Medicine at B.U. Medical School, and a member of the faculty at the Warren Alpert School of Medicine at Brown University. He is a recipient of the CAS Distinguished Alumni Award. His wife, Lori, attended with him.
The Department of Chemistry would like to share the great news that Professor Adrian Whitty has received tenure. Adrian Whitty has taken a non-traditional route to an academic research and teaching career. He joined the Department in April 2008 at the level of Associate Professor without tenure. He came to BU after 14 years of research at the biotechnology company, Biogen (Cambridge MA), where he rose to the position of Director in the Drug Discovery Department. Since joining the Department of Chemistry, Professor Whitty has established a strong, interdisciplinary research program in important areas of quantitative physical biochemistry. His research at Biogen served as the foundation for his current studies in the activation mechanisms of growth factor receptors and the biophysical nature of protein-protein interactions, which are highly important to the development of small-molecule therapeutics. Professor Whitty’s program is distinctive in that it brings quantitative analysis to the study of biological problems that traditionally have been approached using qualitative approaches.
A recipient of the Templeton Prize for Excellence in Student Advising (2011), Adrian Whitty is an outstanding teacher and mentor for graduate and undergraduate students. He has successfully launched the careers of graduate and postdoctoral associates alike. He is also an integral member of the Molecular and Cellular Biology and Biochemistry (MCBB) Program, the Bioinformatics Program, and the Biomolecular Engineering Research Center.
Adrian Whitty received his bachelor’s degree in Chemistry from King’s College, University of London (B.Sc., hon) in 1995, and his M.S. (1988) and Ph.D. (1991) in Organic Chemistry from the Department of Chemistry, University of Illinois at Chicago. He carried out his postdoctoral studies (1990-1993) at Brandeis University in the laboratory of Professor William P. Jencks. He subsequently joined Biogen where he held the positions of Scientist II, Protein Engineering Department (1993 – 1998), Senior Scientist, Drug Discovery Department (1999 – 2002), Associate Director & Head, Physical Biochemistry (2003 – 2007), and Director, Physical Biochemistry (2007- 2008). Since coming to BU, he has been successful in obtaining support from the National Institutes of Health and from various sponsors in the pharmaceutical and biotechnology sectors.
Chemistry faculty, John Snyder and Binyomin Abrams, in conjunction with colleagues in the Departments of Biology (Kathryn Spilios and John “Chip” Celenza) and Neuroscience (Paul Lipton and Lucia Pastorino) have successfully proposed ideas to develop integrated, inquiry-based laboratory courses for first and second year biology, chemistry, and neuroscience students. Jointly funded by the Office of the Provost, the Center for Excellence & Innovation in Teaching, and the College of Arts and Sciences, these interdisciplinary course development grants aim to promote faculty and student collaboration across disciplines in support of innovative, research-oriented undergraduate laboratory education. The new courses that are being developed, Integrated Science Experience 1 (ISE 1) (for second semester freshmen) and ISE 2 (for first semester sophomores), will facilitate students making connections across biology, chemistry, and neuroscience early in their undergraduate careers. Such interdisciplinary insights will better prepare for advanced courses and undergraduate research. Developed in 2015, the courses are anticipated to start in the Spring 2016, and Fall 2016 terms, respectively.
Prof. Emer. Morton Z. Hoffman has received the Distinguished Contribution to Chemistry Education (DCCE) Award from the Committee on Chemistry Education (CCE) of the International Union of Pure and Applied Chemistry (IUPAC) on the occasion of the 23rd International Conference on Chemistry Education (ICCE) in Toronto, Ontario, Canada (July 13, 2014).
The DCCE Award recognizes outstanding contributions with both local and international impact by a chemistry educator to improve the teaching and learning of chemistry. Previous recipients of the award have been Peter Atkins (Oxford University, U.K.), Lida Schoen (Young Ambassadors of Chemistry, Netherlands), Peter Mahaffy (King’s University College, Canada), and Robert Bucat (University of Western Australia).
Morton Hoffman was promoted to emeritus in 2005 after a 44-year, highly productive career in research and teaching in Boston University’s Department of Chemistry. In 1994, he received the University’s highest teaching honor: the Metcalf Cup and Prize for Excellence in Teaching. His many other honors and awards have included being named a Fellow by the ACS, AAAS, and IUPAC; receiving the 2007 ACS Volunteer Service Award, the 2002 Catalyst Award for Teaching Excellence from the American Chemistry Council, the 2003 Timm Award for Encouraging Young People to Study Chemistry from the New England Association of Chemistry Teachers, the 2005 Norris Award for Outstanding Achievement in the Teaching of Chemistry from the Northeastern Section, and the 2006 Outstanding Professional Achievement Award from the Alumni Association of Hunter College of the City University of New York. He was chair of the Northeastern Section in 2002 and of the ACS Division of Chemical Education in 2005.
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.