The Department of Chemical and Systems Biology explores the molecular mechanisms that underlie cellular function and contribute to human disease. Our laboratories emphasize interdisciplinary research that spans the biomedical sciences, including signal transduction, cell cycle regulation, chromatin remodeling, protein homeostasis, metabolism, and cell differentiation. By integrating genetic technologies, biochemical and chemical tools, quantitative measurements, and computational modeling, we strive to deconstruct these complex biological systems, predict emergent behaviors, and translate these discoveries into new medical therapies.
The Chemical and Systems Biology Graduate Program trains students to explore the function of complex biological systems at a quantitative and molecular level. Research in our laboratories combines state-of-the-art approaches from chemistry, biochemistry, cell biology, genomics, computational modeling, and other disciplines to understand cellular and organismal physiology, predict emergent behaviors, and translate these discoveries into new technologies and therapies. Our faculty members are internationally renowned scientists who foster an innovative and collaborative research environment, and alumni from our home program are leaders in academics, biotech, and science policy.
Postdoctoral fellows are an integral part of the Chemical and Systems Biology community, playing active roles in its research and training activities. Fellows join the Chemical and Systems Biology Postdoctoral Program through individual laboratories, and interested applicants should contact faculty members directly.
Developmental signaling pathways and their roles in embryonic patterning and oncogenesis; zebrafish models of tissue patterning and regeneration; synthetic chemistry and chemical biology.
TBX16 Regulates Hox Gene Activation In Mesodermal Progenitor Cells.
Chistol Lab is using real-time single-molecule imaging to: (i) study how eukaryotes replicate/repair their DNA, (ii) dissect molecular mechanisms involved in maintaining large/complex genomes, and (iii) understand how massive multi-subunit molecular machines like the replisome are regulated.
The CMG Helicase Bypasses DNA-Protein Cross-Links to Facilitate Their Repair.
Genome stability pathways and their roles in cancer and other human diseases; DNA damage response pathways and DNA replication; the interface between RNA processing and transcription with genome stability.
Transcription-Replication Conflict Orientation Modulates R-Loop Levels and Activates Distinct DNA Damage Responses.
Cell cycle regulation, especially M-phase regulation, in Xenopus embryos and mammalian cell lines; systems biology of signal transduction pathways.
Thresholds And Ultrasensitivity From Negative Cooperativity.
Targeted protein degradation (TPD) refers to the use of small molecules to induce ubiquitin-dependent degradation of proteins. TPD is of interest in drug development, as it can address previously inaccessible targets...
Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development
Translation of promising research discoveries into novel therapeutics and diagnostics; discovery and development of new drugs, biologics, and diagnostics; repurposing existing drugs against new targets for new clinical indications.
A Practical Guide to Drug Development in Academia: the SPARK Approach.
Protein conformational switches in evolution, disease, and development; molecular mechanisms driving mutational robustness in pathogens and cancer in complex cellular systems; chemical biology, cell signaling, and quantitative genetics.
Intrinsically Disordered Proteins Drive Emergence And Inheritance Of Biological Traits.
The Martinez lab studies RNA regulatory mechanisms that control gene expression. We focus on mRNA processing, RNA modifications and their roles in development and disease.
Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing.
Protein kinase C signaling in normal & disease states; mitochondrial function and dynamics in normal & disease states; oxidative stress and aldehydic load; protein-protein interaction; drug discovery.
Engineered Substrate-Specific Delta PKC Antagonists to Enhance Cardiac Therapeutics.
How are nutrients recognized by their protein sensors? How is their transport across cellular and intracellular membranes regulated? And, how is nutrient sensing integrated with other chemical signals, such as hormones, to determine cellular decisions, especially the decision: to grow or not to grow? We are a team of structural and chemical biologists aiming to answer these questions at the level of ångstroms, nanometers, and micrometers. Many proteins in these pathways are deregulated in cancer, and we are developing targeted chemical probes to modulate their activity in cells and organisms.
Structural basis for the docking of mTORC1 on the lysosomal surface.
Cellular mechanisms responsible for protein quality control surveillance and degradation; invention of new technologies to enable biomedical research; synthetic chemistry and chemical biology.
A method to rapidly create protein aggregates in living cells.
Epigenetic regulation of development; cis-regulatory elements; chromatin modification and remodeling; stem cell self-renewal and differentiation; neural crest and formation of the human face.
Ever-Changing Landscapes: Transcriptional Enhancers In Development And Evolution.