- Research Overview
- Chemical Biology and Medicinal Chemistry
- Chemical Biology and Medicinal Chemistry Overview
- Discovering Enzyme Substrates and Functions
- Discovering Protein Ligands to Probe and Alter Function
- Discovering Enzyme Activators
- Analyzing Mechanisms of Drug Resistance via Chemical Biology
- Analyzing Enzyme Conformational Dynamics, Substrate Binding, and Catalysis
- Effective Drug Targeting of Pathogens via Medicinal Chemistry
- Computational Chemistry and Biology
- Computational Chemistry and Biology Overview
- Modeling protein regulation via allostery and post-translational modifications
- Visualizing and integrating bioinformatics and biomolecular data
- Modeling membrane permeation to optimize pharmacokinetics
- Determining enzyme function by predicting substrate specificity
- Physical Biology
- Protein and Cellular Engineering
- Protein and Cellular Engineering Overview
- Monitoring enzyme activity and disease biomarkers
- Generating human proteome antibodies via phage display and directed evolution
- Globally analyzing and dissecting apoptosis
- Proximity tagging of protein-protein interactions
- Investigating cellular interactions in tissues
- Creating fluorescent probes targeting the genome and key bio-pathways
- De novo design of catalytic and membrane proteins
- Probing and modulating membrane proteins
Department plan 2014-2019
The four Department of Pharmaceutical Chemistry goals for 2014-2019 are highly synergistic and require intense collaborations, even though they are presented separately here and involve unique areas of expertise. Most principal investigators in the department have one or more significant collaborations with other department and UC San Francisco researchers, and the department is the home base for enabling technology centers that attract campuswide collaborative activities. Although the Department of Pharmaceutical Chemistry is disease agnostic, faculty members are passionate about the application of their research to the ultimate understanding and treatment of human diseases. Our plans reflect that passion.
The department aims to accomplish its goals through recruitment, collaboration, and funding, and through the continued development of research technologies in six major department-run enabling technology centers:
- Antibiome Center
- National Bio-Organic Biomedical Mass Spectrometry Resource Center
- Nuclear Magnetic Resonance Laboratory (NMR Lab)
- Resource for Biocomputing, Visualization, and Informatics (RBVI)
- Small Molecule Discovery Center (SMDC)
Interface massive data streams with powerful new computational methods that model, visualize, and predict complex cellular and organismal behaviors
In particular, we will focus on higher-level systems problems and more detailed force field analysis and molecular docking problems. The department has a long and storied history as a pioneer in the use of computers in biology. From the first visualization of protein structures to predicting binding interactions and protein folds, Department of Pharmaceutical Chemistry scientists were there. Computational sciences can now be powerfully applied to solving complex problems in biology. These problems range from discovering the structures and affinities that molecules have for one another to predicting emergent behaviors in cells from the multitude of signaling pathways linked in larger organizational scales.
Solve important problems in biology with chemistry and chemical technologies
We will emphasize the development of lead compounds that are on the path to drug discovery. This goal intersects beautifully with the mission of the department’s Small Molecule Discovery Center, which provides discovery tools, expertise, training, and service for identification of small molecules for biological applications to the entire UCSF community.
The department’s first hires in the field of pharmaceutical chemistry were physical and medicinal chemists with little connection to the mechanistic biology that underpins drug action or disease. This has changed radically over the years. Chemistry is now a powerful tool for penetrating important problems in biology. Pharmaceutical chemistry provides the nexus of leadership in chemical biology from both research and educational perspectives. Our faculty members in this area are arguably the strongest in the field.
Use protein design to reveal complex signaling networks, develop biomarkers for cancer, design nano-materials and cell-cell interactions to understand how tissues are assembled, and participate in the development of new biotherapeutics
The advent of site-directed mutagenesis gave birth to the field of protein engineering and de novo protein design. This powerful technology has transformed our ability to probe protein function and folding and to build new activities that fuel the biotech industry. We aim to take protein and cellular engineering to new levels. As evidence of our ability, one of our faculty members built the first protein from scratch; another probed catalytic and specificity residues for proteases; and a third engineered new catalytic properties, enzyme specificity, and protein-protein interactions. We are designing new cell-cell interactions and new ways to create visual and distance probes for cell biology.
Expand our work in mass spectrometry and the general area of protein structure
The department has a rich history at the interface of physics and biology. Nuclear magnetic resonance has been a traditional strength, and the department is a pioneer in the development of mass spectrometry in biology. One of our newest faculty members co-developed the highest resolution 3D light microscopy methodology, STORM, as a postdoctoral scholar, and now at UCSF is further developing this technology to probe membrane, cytoskeletal, and nuclear protein structures in cells.
Our plans in context
The plans developed and executed by the Department of Pharmaceutical Chemistry support the broader School of Pharmacy strategic plan. These in turn support the UCSF's strategic plan. All UCSF plans support the continued success of the 10-campus University of California system.