Currently, my laboratory focuses on the CRISPR-Cas system, an RNA-based adaptive immune system found in bacteria that protects against invasion by viruses and plasmids. Mechanistic studies of the CRISPR-Cas system is contributing to ongoing efforts aimed at exploiting this system to both protect domesticated bacteria (such as those used in food and pharmaceutical production) and combat human pathogens and the spread of antibiotic resistance. Moreover, RNA-guided nucleases from the CRISPR-Cas system are currently being adapted for genome editing and regulation strategies in a wide variety of organisms, including humans. Indeed, the potential of the CRISPR-Cas toolkit is just being realized and studies centered on understanding how the CRISPR-Cas systems function represents an important need. To this end, my laboratory has provided structural and mechanistic insight into how CRISPR-Cas systems identify and destroy their DNA targets.
We seek to understand the molecular mechanisms of macromolecular assemblies that organize, express, and preserve the cell’s genetic information. We are particularly interested in developing kinetically accurate, atomic-resolution depictions of the dynamic assemblies that control DNA replication, gene regulation, and chromosome superstructure, and in exploiting this knowledge for chemotherapeutic development.
The Dang lab contributed to defining the function of the MYC oncogene including establishing the first mechanistic link between MYC and cellular energy metabolism. This foundational concept that genetic alterations in cancers re-program fuel utilization by tumors provides a framework to develop novel strategies for cancer therapy. Current lab interests include seeking metabolic vulnerabilities of cancer and define how the circadian molecular clock influences cancer metabolism, immunity, tumorigenesis and therapeutic resistance. The molecular and metabolic basis for pancreatic cancer cell immune evasion is an ongoing area of investigation.
The ribosome is a complex molecular machine that translates the genetic code into functional polypeptides. Our research focuses on understanding how the ribosome functions at a molecular level and how changes in its activity lead to mRNA quality control and the induction of cellular stress responses. Work in the Green lab ranges widely in scope, from detailed mechanistic questions in ribosome rescue to surveying global changes in gene expression and dissecting the complex interplay of mammalian signaling pathways.
My laboratory aims to understand the molecular mechanisms regulating eukaryotic signaling of pathways. This knowledge provides the framework needed to interpret how alterations to a pathway, such as additional proteins, mutations to pathway components, or small molecules, modulate activity and could help guide targeted therapies. To achieve this, my lab employs a multi-prong approach that combines cell-based assays, biochemistry, enzymology, biophysics, and structural biology.
My laboratory aims to understand the molecular mechanisms regulating eukaryotic signaling of pathways. This knowledge provides the framework needed to interpret how alterations to a pathway, such as additional proteins, mutations to pathway components, or small molecules, modulate activity and could help guide targeted therapies. To achieve this, my lab employs a multi-prong approach that combines cell-based assays, biochemistry, enzymology, biophysics, and structural biology.
The Leung Lab studies gene regulation using multi-disciplinary and quantitative imaging, genomics and proteomics approaches, to uncover novel roles of RNA metabolism, biomolecular condensates, and post-translational modifications.
We develop technology, such as proteomic and single-molecule tools to dissect the roles of a post-translational modification called ADP-ribosylation. My lab seeks to translate our basic scientific findings to disease therapy, e.g., PARP inhibitors in cancers and macrodomain inhibitors to fight Chikungunya viral infection and COVID-19.
Our primary research interest lies at the interface between chemistry, biology, and medicine. We employ high-throughput screening to identify modulators of various cellular processes and pathways that have been implicated in human diseases from cancer to autoimmune diseases. Once biologically active inhibitors are identified, they will serve both as probes of the biological processes of interest and as leads for the development of new drugs for treating human diseases.
Among the biological processes of interest are cancer cell growth and apoptosis, angiogenesis, calcium-dependent signaling pathways, eukaryotic transcription and translation.
Research in the Matunis laboratory is focused on understanding the molecular mechanisms regulating the modification of proteins by the small ubiquitin-related modifier (SUMO) and the consequences of SUMOylation in relation to protein function, cell behavior and ultimately, human disease. Particular interests include understanding how SUMOylation regulates cell cycle progression, DNA damage repair, nuclear import and export, and cell stress response pathways. We have studied SUMOylation in mammalian cells, yeast and the malaria parasite, P. facliparum, using a variety of in vitro biochemical approaches, in vivo cellular approaches and genetics.
My laboratory is broadly interested in how dNTP pool levels and composition influence genetic stability, adaptive and innate immunity, inflammation, carcinogenesis, cellular senescence and aging. Current work in the lab focuses on elucidating how the dNTPase and DNA/RNA binding activities of the enzyme SAMHD1 lead to HIV-1 restriction in macrophages, anticancer drug resistance, and cellular DNA repair. Our long-range goal is to design novel small molecules that inhibit or activate the various activities of SAMHD1 in cells for antiviral, anticancer, and anti-inflammatory therapeutic uses.
The Wang lab is interested in the biological basis for protein and RNA homeostasis in neurodegeneration. We hope to solve problems that not only have biological significance but also have important implications for understanding and treating disease. Our work focuses on three main areas: discovering key regulators of protein homeostasis, uncovering novel players in the regulation of RNA homeostasis, and revealing the mechanisms of neurodegenerative diseases including those caused by repeat expansions.