Research Areas

The UCSF Pharmaceutical Sciences and Pharmacogenomics Graduate Program offers six areas of research emphasis:

  1. Pharmacogenomics and functional genomics
  2. Quantitative and systems pharmacology
  3. Computational genomics
  4. Molecular pharmacology
  5. Drug development sciences
  6. Therapeutic bioengineering

1. Pharmacogenomics and functional genomics

Pharmacogenomics and functional genomics are increasingly recognized scientific areas that are critical to precision medicine. PSPG faculty are internationally recognized in the fields of pharmacogenomics, functional genomics and precision medicine. In particular, a significant number of our training faculty have NIH funded grants in pharmacogenomics and functional genomics. Notably, we recently procured a U01 grant to be the hub for coordinating the scientific activities of the new NIH Pharmacogenomics Research Network (K. Giacomini, GM115370, 2015-2020). Pharmacogenomic and human genomic research is undertaken in addiction, liver disease, asthma, cardiovascular disease, diabetes, psychiatry, HIV, cancer and autism. Research involves state of the art genomic technologies, including genome-wide genotyping, exome and whole genome sequencing, RNA-seq, ChIP-seq and additional ‘seq’ technologies in large and ethnically diverse patient populations collected at UCSF and world-wide. Students working on pharmacogenomic projects are often involved in multi-investigator research and have opportunities for interactions with a broad range of scientists spanning the clinical to basic spectrum. Most investigators have a significant emphasis on functional genomic studies to understand the molecular basis of genetic associations with drug response and toxicity. Functional genomic studies involve cell-based systems, model organisms, induced pluripotent stem cells and analysis of human tissues. Interest in understanding genetic variation in noncoding regions relies heavily on ChIP-seq, RNA-seq, and CRISPR technologies.

Program faculty members working in this area are:

2. Quantitative and systems pharmacology

The explosion of data, driven by technological advances in genomics, proteomics, metabolomics, epigenomics and related fields, coupled with advances in data integration from the molecular to whole organism level has fueled research in quantitative and systems pharmacology. Research in this area underlies advances in precision medicine and is an area of growth within the PSPG program. Some faculty are involved in high throughput screens of chemical libraries with collection of phenotypes at the molecular, cellular and whole organism level. Others are focused on the development of integrated models to explain drug response and disease progression in humans. The repurposing of drugs for new therapeutic indications is another new area of research in this field. Students working in quantitative and systems pharmacology often have both computational and experimental components to their dissertation research.

Program faculty members working in this area are:

3. Computational genomics

Complementing our strengths in pharmacogenomics are emerging strengths in computational genomics. A number of PSPG faculty are focused on the development and application of computational methods to mine large omics datasets for investigating variability in drug response and disease risk and for understanding basic mechanisms underlying disease. Many of these investigators utilize large publically available datasets like 1000 Genomes and ENCODE in developing robust and efficient computational methods that correlate and display genome-wide data. A number are inaugural members of the new UCSF Institute for Computational Health Sciences, established as the cornerstone for precision medicine at the institution. Students working in this area develop strong computational skills that can be applied to critical questions related to optimal drug design, development and use.

Program faculty members working in this area are:

4. Molecular pharmacology

There has been a resurgence in molecular pharmacology at UCSF as the discoveries in pharmacogenomics and systems pharmacology are translated into a mechanistic understanding of drug action. Molecular Pharmacology research utilizes model organisms and cellular systems to explore drug-induced cell signaling and mechanisms of drug-induced toxicity. A deep understanding of the cellular signaling pathways underlying normal cell and organ function and alterations during disease serves as the basis for testing new and established therapeutic agents. Chemical libraries are often tested to identify new therapeutic targets. Pharmacology expertise is found broadly across medical disciplines, including cancer, CNS diseases, HIV, cardiovascular, renal and pulmonary. Students working in molecular pharmacology labs develop strong molecular and cellular biology skills and often interact with chemists and computational biologists.

Program faculty members working in this area are:

5. Drug development sciences

The PSPG graduate program, and before that the Pharmaceutics pathway of the Pharmaceutical Chemistry graduate program, is internationally recognized for training in the drug development sciences. Recently, we have added a new area of research, regulatory sciences, to drug development sciences through procurement of a large center grant in regulatory sciences and innovation, CERSI, funded by the FDA. This center provides funding for pilot proposals in innovative research in drug development and regulatory sciences and offers numerous educational seminars and workshops available to the campus community. Faculty members in this research group have broad expertise in pharmacokinetics, pharmacodynamics, drug metabolism and transport, and clinical pharmacology. Active areas of research include drug transporter function, regulation and variability, interplay between transporters and metabolizing enzymes in drug absorption and elimination, the clinical pharmacology of drugs used for the treatment of addiction, diabetes, infectious disease, organ transplantation and cancer, the use of biophysical methods to predict absorption, distribution, metabolism and excretion of new chemical entities, and the development of biomarkers of drug response and toxicity. Research involves whole organism studies in preclinical animal models and humans as well as molecular and cellular studies of drug action. Pharmacometric research on integrated pharmacokinetic-pharmacodynamic models describing drug response and disease progression has important applications in precision medicine and clinical trial design. Students completing dissertation research in drug development sciences develop experimental and computational skills and knowledge that are critical for preclinical and clinical drug development.

Program faculty members working in this area are:

6. Therapeutic bioengineering

A small but dynamic group of faculty are part of the therapeutic bioengineering research group. Research in this area has expanded from a traditional focus on liposomal drug delivery to include areas related to drug devices, imaging and microfluidics. Research includes the use of droplet-based microfluidics for directed evolution and single cell gene expression profiling. In addition to applications in basic science research, microfluidics have enormous promise for medical diagnostics. Research into vaccine, drug and nucleic acid delivery systems, the design and fabrication of micro and nano systems for drug targeting and delivery, the use of BioMEMs devices for tissue repair, artificial organs, diagnostics and delivery, and applications of imaging for studying disease pathogenesis and progression, as diagnostic tools and for monitoring drug response are undertaken by these investigators. Pharmacokinetic and pharmacodynamic principles are incorporated into many of these studies. Most laboratories have a fertile training environment for students with either a biology or engineering background. Students mentored by faculty members in therapeutic bioengineering typically undertake experimental work that integrates cellular and molecular approaches with bioengineering tools.

Program faculty members working in this area are: