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Alice C. Fan
Assistant Professor of Medicine (Oncology) and, by courtesy, of Urology
Current Research and Scholarly InterestsDr. Fan is a physician scientist who studies how turning off oncogenes (cancer genes) can cause tumor regression in preclinical and clinical translational studies. Based on her findings, she has initiated clinical trials studying how targeted therapies affect cancer signals in kidney cancer and low grade lymphoma. In the laboratory, she uses new nanotechnology strategies for tumor diagnosis and treatment to define biomarkers for personalized therapy.
Associate Professor of Biology
Current Research and Scholarly InterestsWe are interested in understanding design principles within cells that contribute to the diversification of cellular form and function. Using a combination of genetic, biochemical, and live imaging approaches, we are investigating how the microtubule cytoskeleton is spatially organized and the mechanisms underlying organizational changes during development.
Dean W. Felsher
Professor of Medicine (Oncology) and of Pathology
Current Research and Scholarly InterestsMy laboratory studies the molecular basis of cancer with a focus on understanding when cancer can be reversed through targeted oncogene inactivation.
Director of Crystallography
BioDot-to-dot on an electron density map, the molecular bricks that sustain life - proteins, nucleic acids, polymers, and their ligands, inhibitors, and co-factors - all initially invisible to the naked eye, come alive on-screen. Connecting these molecules to what they do in life inspires research and development. At the Macromolecular Structure Knowledge Center (MSKC) you will find a platform to explore, expand, and enrich our understanding on how natural processes and technology work at the level of the atom.
Associate Professor of Bioengineering and of Medicine (Microbiology and Immunology)
Current Research and Scholarly InterestsThe human microbiome is linked to a range of phenotypes in the host, but it remains difficult to test causality and explore the mechanisms of these interactions. Our lab focuses on two research areas that share a common goal of studying host-microbiota interactions at the level of molecular mechanism:
1) Technology development. Much of what we know about biology has been learned by deleting individual genes from mice, worms, flies and yeast. The ability to do single-strain and single-gene deletion in the microbiome would be transformative but does not yet exist. We are developing technology in three areas to make this possible:
Synthetic ecology: There is a pressing need for model systems for the microbiome that are defined, but of an order of complexity that approaches the native state. Key experiments in the field often show that a host phenotype can be transferred to a germ-free mouse via fecal transplant. If these phenomena could be recapitulated with a defined, high-complexity community, then reductionist experiments to probe mechanism would be possible. We are developing the technology required to build highly complex defined communities (100-200 bacterial species), make them stable upon transplantation into mice, and probe their function in vitro and in vivo.
Genetics: It is difficult to probe mechanism without genetics, and genetic tools exist for only ~10% of the bacterial species in the gut and skin microbiome. We are developing technologies that will make it possible to delete and insert genes, and build mutant libraries, in many of the most common bacterial strains in the gut and skin microbiome.
Computation: In previous work from the lab, we have developed computational algorithms that identify small-molecule-producing genes in bacterial genomes. In current work, we are devising algorithms for genome mining that are specific to the microbiome, and new tools for predicting the chemical structures of small molecules from untargeted metabolomics data.
2) Molecular mechanisms. Many of the early findings in microbiome research are correlative or associative. We are applying the tools described above to explore the mechanisms underlying these phenomena:
Small molecules: Our lab has had a long-standing interest in small molecules from the microbiota. These include: 1) host-derived molecules metabolized by the microbiome, like bile acids; 2) characteristic components of the bacterial membrane and cell wall, including LPS and capsular polysaccharides; and 3) hundreds of other diffusible small molecules (e.g., the products of polysaccharide and amino acid metabolism) that are present in the bloodstream at high concentrations. Our work in this area seeks to establish the mechanisms by which these molecules modulate host biology, especially by deleting them one at a time in the background of a complex community; and to discover new microbiome-derived metabolites present in the bloodstream and host tissues.
Ecology of complex communities: Synthetic ecology at the 100+ strain scale is entirely unexplored, and the emergent properties of complex communities are not well understood. Our work in this area seeks to understand basic principles outlined by the following questions: How many meaningful interactions exist in a community of hundreds of strains? What constitutes a niche, molecularly and spatially, and how do strains map to niches? What are the molecular correlates of stability, and how does a community reconfigure in response to a perturbation? How rare or common are stable states, and how predictable is the process by which a consortium will evolve toward a stable state? To what extent do priority effects (early colonists and events) determine the outcome of ecosystem development? Can the results of ecosystem competition be predicted or engineered?
Assistant Professor of Bioengineering and of Genetics
Current Research and Scholarly InterestsThe Fordyce Lab is focused on developing new instrumentation and assays for making quantitative, systems-scale biophysical measurements of molecular interactions. Current research in the lab is focused on three main platforms: (1) arrays of valved reaction chambers for high-throughput protein expression and characterization, (2) spectrally encoded beads for multiplexed bioassays, and (3) sortable droplets and microwells for single-cell assays.
Donald Kennedy Chair in the School of Humanities and Sciences and Professor of Genetics
Current Research and Scholarly InterestsThe long term goal of our research is to understand how proteins fold in living cells. My lab uses a multidisciplinary approach to address fundamental questions about molecular chaperones, protein folding and degradation. In addition to basic mechanistic principles, we aim to define how impairment of cellular folding and quality control are linked to disease, including cancer and neurodegenerative diseases and examine whether reengineering chaperone networks can provide therapeutic strategies.