Chemical Biology

Research includes:

  • Biocatalysis
  • Cellular Regulation
  • Drug Delivery
  • Drug Discovery
  • Glycobiology
  • Lipid Biochemistry
  • Metalobiochemistry
  • Molecular Recognition
  • Protein Folding and Assembly
  • Protein Trafficking
  • Receptor Pharmacology

Training Group Mission:

Students who join this training group work with a diverse group of faculty that apply chemical-based approaches to further the understanding of living systems. Fundamental and technical advances in chemistry, biochemistry, and structural and molecular biology over the past several decades have provided unprecedented opportunities to probe living systems at a molecular level. These advances have led to the development of a rapidly growing multidisciplinary field - Chemical Biology. Within the Chemical Biology training group, students apply groundbreaking chemical methodology to the elucidation of essential biological processes. Additionally, students that have identified new biological targets will drive the development of unique chemical entities. All students receive broad training at the interface of chemistry and biology, allowing the student to master the concepts needed for success in this multidisciplinary area of research.

Faculty Membership

Research Area

We are synthetic organic and medicinal chemists with three predominant interests: (1) Exploring physicochemical and biophysical perturbations imparted by fluorinated functional groups and applying these groups towards drug design; (2) Providing medicinal chemistry support for pharmacological experts, particularly towards treating pain, mood and anxiety disorders, aging, and inflammation; (3) Developing innovative synthetic organic reactions for accessing therapeutically relevant drug-like compounds.

Our research is focused on the synthesis of complex glycoproteins, natural products, and oligosaccharides of importance in immunology and oncology. Ideally, in direct collaboration with biologists and clinicians, this will lead to the identification of lead structures as pharmacological tools and potential therapeutics.

Protein structure and function; X-ray crystallography; metalloenzymes; biodegradation of PCBs and related compounds

The Chan Lab believes that understanding the early response to injury is critical to diagnosis, assessment, and intervention in life-altering diseases, including post-traumatic osteoarthritis and traumatic brain injury. True to our biomedical engineering roots, we adopt a multi-disciplinary approach - using biomechanics, biomedical imaging, and matrix biology - to quantify the complex tissue responses to injury.

Development of small molecules, peptides and peptidomimetics for drug discovery, bionanotechnology, and cellular delivery of therapeutic agents

Chemical Immunology: Cell specific chemical perturbation of immune microenvironments in cancer, neurological and immunological disorders

Chemical synthesis and biological evaluation of natural products with medicinal importance and novel, diverse and complex small molecule libraries; medicinal chemistry; mechanism of action study.
Functional role deubiquitinating enzymes in cellular pathways implicated in neurodegeneration, such as Alzheimer's disease and Parkinson's disease
Chemical and systems biology as applied to drug discovery; design, synthesis, and evaluation of small molecule modulators of protein interactions; development and application of high content cell analysis screening platforms.
Our major goal is to understand how the misregulation of chromatin leads to cancer progression. A major focus for the lab is on chromatin targeting subunits of chromatin remodeling complexes, in particular the heterogeneous collection of SWI/SNF chromatin remodeling complexes. We have determined that Polybromo 1 (PBRM1), a chromatin targeting subunit of the PBAF subcomplex, is important for the transcription of stress response genes in renal cancer, and that BRD9, a chromatin targeting subunit of the recently characterized GBAF (or ncBAF) subcomplex, is required for androgen receptor signaling in prostate cancer. Another focus of the lab is on the CBX chromatin targeting subunit of Polycomb repressive complex 1, which is represented by five CBX paralogs in mammals. We have made significant progress in establishing glioblastoma's dependence on CBX8 expression for viability, defining downstream targets of CBX8, and defining the contribution of the chromodomain to CBX8 targeting. Our current goal is to use our recently developed CBX8 inhibitors in combination with biochemical and proteomic approaches to connect paralog-specific biochemical function for CBX8 to a paralog-specific role in glioblastoma.
Use of chemistry as a tool to elucidate biological mechanisms
Synthetic organic, bioorganic and medicinal chemistry
Structural basis for RNA function
Multidrug resistance in human cancer
Design and synthesis of chemical inhibitors to interrogate epigenetic pathway towards development of new therapeutic agents
Organic and bioorganic mass spectrometry
bio-organic chemistry, bioconjugate chemistry, in vitro evolution, drug discovery
Computer-assisted drug design
Organic synthesis, bioorganic chemistry and molecular modeling
Epigenetic regulation of transposable elements
Structure-Function relationships of natural product biosynthetic enzymes for combinatorial biosynthesis
We develop targeted drugs for many different diseases including cancer, pulmonary fibrosis, rheumatoid arthritis, sickle cell disease, malaria, Crohn's disease, type 1 diabetes, many viral infections, organ transplant rejection, and depression. Our experimental methods include everything from characterization of disease mechanisms to design, synthesis, in vitro testing and in vivo validation of new drugs to treat these diseases.
Quantification of cellular activation thresholds in cancer and immune cells that interact within the complex, dynamic tumor microenvironment. Measurement of the molecular impulse-response function with single molecule and single cell precision.
DNA Nanotechnology and Its Application

In the Parkinson lab, we focus on the discovery of novel antibiotic and anticancer natural products from cryptic biosynthetic gene clusters found in soil dwelling

The Rochet lab has a long-standing interest in neurodegenerative disorders including PD, DLB, and AD. We have adopted the approach of detailed characterization of proteins linked pathologically and/or genetically to these disorders. We aim to elucidate mechanisms of neurodegeneration relevant to both familial and more common sporadic forms of these diseases.
Drug Discovery in Cancer and Alzheimer's Disease Using Chemical Biology Tools

1) Cyclic dinucleotide signaling in bacteria and immune cells. 2) Bacterial quorum sensing. 3) Inhibitors of protein kinases (examples are: FLT3, ABL1, ROCK1/2, LRRK2, RET, CDKs). 4) Novel antibacterial and anti-biofilm agents.

Regulator of G protein signaling (RGS) proteins regulation by ubiquitin-proteasomal degradation and post-translational, transcriptional and epigenetic mechanisms. RGS protein drug discovery.
We primarily study the molecular basis of GPCR-mediated signal transduction, principally via the techniques of X-ray crystallography and single particle electron microscopy. By determining atomic structures of signaling proteins alone and in complex with their various targets, we can provide important insights into the molecular basis of signal transduction and how diseases result from dysfunctional regulation. The lab is also interested in rational drug design and the development of biotherapeutic enzymes.
Our group creates new organic materials for applications in drug delivery and affinity capture for high-resolution cryoelectron microscopy using a design-build-test development cycle for their performance optimization. High-throughput experimentation methods are also used in our lab to select the most promising reaction conditions for executing the continuous synthesis of drug molecules in a manner that can be rapidly upscaled to support preclinical and clinical studies.
The Trader laboratory seeks to develop tools to harness the proteasomal machinery to facilitate clearance of diseased cells, especially cancer and virus-infected cells. Our research program will seek to identify compounds that enable us to stimulate, rescue, inhibit, and direct protein degradation of the proteasome. We anticipate discovering compounds that target the proteasome through unprecedented mechanisms of action. Our innovative strategies for the discovery of small molecules that interact with the proteasome will be translated to new therapeutics and tools.
Organic synthesis, nanostructured materials science, self-assembly principles to produce exotic materials with physical or biomimetic function
Marine biological materials: biology, biochemistry, chemistry, polymers, and materials engineering
Plant endomembrane trafficking; chemical biology
Protein tyrosine phosphatases, cellular signaling mechanism, cancer biology, chemical and structural biology, drug discovery, protein structure and function.

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