Chemical Biology utilizes small molecules to probe and manipulate biology, and faculty who make use of the approaches of chemical biology are active in many of the traditional disciplines of biochemistry, including biophysics, mechanistic enzymology, metal ion transport and biochemical signaling and signal transduction. Practitioners of Chemical Biology are also leaders in the development of novel experimental techniques and approaches, including chemical synthesis, structural biology and the development of novel omic technologies.
The faculty of the Program in Chemical Biology hail from various Departments across the School of Medicine and the Faculty of Arts & Sciences. Researchers use a variety of techniques, including chemical synthesis, structural biology, biophysical chemistry, to address a range of problems in biology, including mechanistic enzymology, signaling and signal transduction and metalobiochemistry. Our faculty is constantly evolving, but currently includes:
Hashim Al-Hashimi: Research in the Al-Hashimi lab ranges from the theoretical design and implementation of new NMR experiments for probing the physicochemical properties of biomolecules, to structure, dynamics, and functional characterization of processes that underlie gene expression and regulation and HIV replication, to high throughput screening and computational docking to identify small molecule that bind and modulate the activity of biomolecules. We are particularly interested in RNA and DNA and the proteins and small molecules that bind to them.
Emily Derbyshire: The Derbyshire lab's goal is to globally interrogate parasite biology by using chemical biology, molecular biology, and biochemistry to characterize the roles of essential proteins. Research in the lab uses chemical tools and biological methods to uncover novel aspects of malaria parasite biology with the ultimate aim of identifying druggable targets. Projects range from developing assays for phenotypic and target-based screens – forward and reverse chemical genetics – to dissecting biological pathways and identifying small molecules with potential therapeutic value. Our interdisciplinary collaborative program integrates both novel and established methods to address target identification, one of the most challenging aspects of malaria drug discovery.
Bruce Donald: Members of the Donald Lab are conducting research in computational biology and chemistry. Some of the most challenging and influential opportunities for Physical Geometric Algorithms (PGA) arise in developing and applying information technology to understand the molecular machinery of the cell. Our recent work shows that many PGA techniques may be fruitfully applied to the challenges of computational molecular biology. PGA research may lead to computer systems and algorithms that are useful in structural molecular biology, proteomics, and rational drug design.
Katherine Franz: The Franz lab studies the functional consequences of metal ion chelation and coordination in biological systems, along with applications of these systems to medicine.
Amanda Hargrove: The Hargrove lab harnesses the unique properties of small organic molecules to study the structure, function and therapeutic potential of long noncoding RNAs (lncRNAs). The discovery of these fascinating biomolecules has caused a paradigm shift in molecular biology and speculation as to their role as the master drivers of diseases such as cancer. At the same time very little is known about their structure and function, leading some to call the field a veritable “Wild West.” Small molecules are the perfect tools for such exploration, and the Hargrove lab works at the interface of chemistry and biology, employing methods ranging from RNA-targeted small molecule synthesis and array-based pattern recognition to studies of the molecular and cellular biology of nucleic acids. Collaborations with the Department of Biology as well as colleagues in the School of Medicine ensure that these tools are applied to the most important unsolved problems in the fundamental biology and disease-related actions of long noncoding RNAs.
Jiyong Hong: Research in the Hong group focuses on using chemical tools, in particular small molecules, to understand the signaling pathways in biology. We synthesize biologically interesting natural products and screen small molecule libraries to identify modulators of biological processes.
Dewey McCafferty: Research interests are broadly based in chemical biology, mechanistic enzymology and molecular medicine. Towards this end our group is engaged in understanding the chemical and kinetic mechanisms, substrate specificity and therapeutic importance of enzymes that posttranslationally modify chromatin, such as histone deacetylases, histone demethylases, histone methyl transferases, and chromatin assembly and remodeling complexes. Building on a mechanistic foundation, our laboratory is also interested in the design, chemical synthesis and evaluation of small molecules to modulate the activity of chromatin modifying enzymes within living cells.
Donald McDonnell: The nuclear receptor superfamily of ligand-regulated transcription factors are the targets of drugs that account for over 20% of all prescriptions written. Within this family of over 40 proteins are receptors that enable cells to respond to steroid hormones, thyroid hormone, retinoids and vitamin D. Also contained in this family are several "orphan receptors" for which specific hormones remain to be identified. The research in our laboratory is focused on defining the mechanism of action of those nuclear receptors whose expression and/or activity is implicated in the pathogenesis of breast and prostate cancer. We have a specific interest in defining the signaling pathways in these cancers in which the estrogen, progesterone and androgen receptors are engaged.
Jennifer Roizen: Inspired by small molecule natural products, the Roizen laboratories will initiate research to access improved antibiotics, and selective ion channel inhibitors, with implications for the study and treatment of cancer, heart disease, and neurological disorders. This program will begin with the development of novel reaction methods, and where appropriate these methodologies will be advanced through mechanistic investigations. New reactions will be designed to streamline access to challenging natural products, such as the guaianolide sesquiterpenes. Access to these small molecules will enable us to collaborate with colleagues to probe the biological activity of these molecular architectures.
Qiu Wang: Research in the Wang group aims to answer fundamental questions that lie at the interface of chemistry and biology. In particular, we are interested in developing small-molecule based probes and methods to understand the cause of disease with an emphasis on identifying potential therapeutic agents towards cancer and neurodegenerative disorders.