CMD wishes to Welcome a new member to the team:
Edith Nagy – postdoc
Edith began her chemistry training at Florida Atlantic University where she received her Bachelor’s degree. She then continued her PhD studies at the same institution (2012) working with Dr. Salvatore D. Lepore as a NSF graduate research fellow. As part of her PhD work, she developed new methods for the synthesis of isoxazolines and pyrazolines and performed detailed studies on the mechanisms of these transformations. During the summers of 2014 and 2015, Edith went for an internship to Eli Lilly & Co. in Indianapolis where she worked on a diabetes related project in the R&D division. She joined BU-CMD as a postdoctoral fellow in November 2017.
Dr. Andrew Emili, Ph.D.
Professor of Biology and Biochemistry
Dr. Emili has recently come to BU by way of the University of Toronto. Dr. Emili brings expertise in the areas of systems biology and proteomics.
BU Today has featured Dr. Emili in his new roles at the School of Medicine biochemistry department and the College of Arts & Sciences biology department.
Thanks to all who attended the 16th Annual CMD Symposium on June 23! Attendees were treated to fantastic talks from Professors Dirk Trauner, Ben List, Frances Arnold and Robert Langer, followed by a poster session highlighting new research from our students and postdocs.
Special thanks to Center Administrator Lisa Holik for a great job organizing this event, our friends at BUnano for help with setup and Prof. Aaron Beeler for organizing the poster session.
Thanks also to our generous sponsors listed below, without whom this event would not be possible:
- Bristol-Myers Squibb
- BU Translational Research in Biomaterials Training Grant
- Eisai Research Institute
- Interchim Inc.
- Paraza Pharmaceuticals
- Pfizer, Inc.
- Strem Chemicals, Inc.
Check back in the future for news on our next CMD Symposium.
Congratulations to Han Yueh, Qiwen Gao, and Professors John Porco and Aaron Beeler on their recent paper in Bioorganic & Medicinal Chemistry entitled “A photochemical flow reactor for large scale syntheses of aglain and rocaglate natural product analogues”
Abstract: Herein, we report the development of continuous flow photoreactors for large scale ESIPT-mediated [3 +2]-photocycloaddition of 2-(p-methoxyphenyl)-3-hydroxyflavone and cinnamate-derived dipolarophiles. These reactors can be efficiently numbered up to increase throughput two orders of magnitude greater than the corresponding batch reactions.
Congratulations to William Devine, Lauren Brown, and Professor John Porco on their recent paper in Science Translational Medicine entitled “Inhibiting the oncogenic translation program is an effective therapeutic strategy in multiple myeloma.”
Abstract: Multiple myeloma (MM) is a frequently incurable hematological cancer in which overactivity of MYC plays a central role, notably through up-regulation of ribosome biogenesis and translation. To better understand the oncogenic program driven by MYC and investigate its potential as a therapeutic target, we screened a chemically diverse small-molecule library for anti-MM activity. The most potent hits identified were rocaglate scaffold inhibitors of translation initiation. Expression profiling of MM cells revealed reversion of the oncogenic MYC-driven transcriptional program by CMLD010509, the most promising rocaglate. Proteome-wide reversion correlated with selective depletion of short-lived proteins that are key to MM growth and survival, most notably MYC, MDM2, CCND1, MAF, and MCL-1. The efficacy of CMLD010509 in mouse models of MM confirmed the therapeutic relevance of these findings in vivo and supports the feasibility of targeting the oncogenic MYC-driven translation program in MM with rocaglates.
Dr. Karen Allen, Ph.D.
Professor of Chemistry
Dr. Allen brings expertise in the areas of X-Ray crystallography and enzyme structure and function to the CMD.
Dr. Sandor Vajda, Ph.D.
Professor of Biomedical Engineering and Chemistry
Dr. Vajda brings expertise in the areas of computational methods and drug discovery to the CMD.
Dr. Arturo Vegas, Ph.D.
Assistant Professor of Chemistry
Dr. Vegas brings expertise in the areas of drug delivery and targeting to the CMD.
Dr. Adrian Whitty, Ph.D.
Associate Professor of Chemistry
Dr. Whitty brings expertise in the areas of biological chemistry and protein-protein and protein-drug interactions to the CMD.
CMD wishes to Welcome two new members to the team:
David Huang – postdoc
Wenhan Zhang – postdoc
Both will be joining the team in October.
Congratulations to Lauren Brown, Mikayo Hayashi and Professor John Porco on their recent Communication in the European Journal of Organic Chemistry entitled “Asymmetric Dearomatization/ Cyclization Enables Access to Novel Chemotypes.”
Abstract: Enantioenriched, polycyclic compounds were obtained from a simple acylphloroglucinol scaffold. Highly enantioselective dearomatization was accomplished using a Trost ligand palladium(0) complex. A computational DFT model was developed to rationalize observed enantioselectivities and revealed a key reactant-ligand hydrogen bonding interaction. Dearomatized products were used in visible light-mediated photocycloadditions and oxidative free radical cyclizations to obtain novel polycyclic chemotypes including tricyclo[4.3.1.01,4]decan-10-ones, bicyclo[3.2.1]octan-8-ones and highly-substituted cycloheptanones.
The National Institutes of Health (NIH) has awarded a four-year grant to Center for Molecular Discovery researcher Lauren Brown and collaborators Leah Cowen (University of Toronto) and Luke Whitesell (Whitehead Institute for Biomedical Research at MIT) on “Targeting Hsp90 in crytococcal fungal pathogenesis.” The assembled team combines expertise in fungal biology (Cowen), medicinal chemistry (Brown) and pharmacology/experimental therapeutics (Whitesell) with the goal of developing drug-like small-molecule probes for use in studying disease mechanisms of the fungus Cryptococcus.
Invasive Cryptococcus infections pose a grave threat to human health and have enormous economic consequences. Cryptococcal meningitis, the major clinical manifestation of the disease, has a 100% mortatlity rate if left untreated. Even with the best available therapies, mortality rates remain high at 35-40% due to a limited number of drug classes available, and compromised usefulness of these drugs caused by both dose-limiting toxicity and the emergence of high-grade antifungal drug resistance.
In this project, the team will collaborate to develop small molecule chemical compounds to study a critical molecular mechanism that supports both fungal virulence and the onset of drug-resistance. These compounds will also impact clinical care by serving as promising leads for the future development of new, more effective antifungal drugs.
The National Institutes of Health, Institute of General Medical Sciences (NIGMS), has awarded Professor John Porco and coworkers 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.