I am looking at how cells ensure that proteins fold into their correct shape, as well as the role of protein misfolding in disease and normal physiology. I am also developing experimental and analytical approaches for exploring the organizational principles of biological systems.
I am the founder and CEO of Unum Therapeutics, which develops novel cellular immunotherapies to treat cancer. Unum has developed an Antibody-Coupled T-cell Receptor (ACTR) that enables a patient’s T cells to be targeted to attack tumor cells via a co-administered tumor-specific antibody. Clinical proof-of-concept for ACTR has been provided in an ongoing clinical study … Continued
Current research in my laboratory is focused on the fundamental mechanisms of ubiquitin signaling and regulation of mRNA transcription, with a focus on the role of histone ubiquitination in regulating transcription and chromatin dynamics. My group uses a combination of structural, biophysical and biochemical approaches to study enzyme complexes involved in these processes.
Our lab is investigating how a variety of life processes are coordinated with metabolism and the metabolic state of the cell. These include gene expression, protein translation, epigenetics, autophagy, and mitochondrial homeostasis. Elucidation of these mechanisms promises to reveal innovative therapeutic strategies for treating cancer and neurodegenerative conditions.
All life relies on chemical reactions that occur within cell membranes, which are structures that form the living border between a cell and the outside world. These reactions range from algae harnessing solar energy through their photosystems to the human brain propagating electrical impulses along its neurons. Guardians of this frontier are specialized, membrane-immersed enzymes, … Continued
How is a cell created from its molecular constituents? Individual proteins are typically only a few nanometers in size. Without a blueprint or an architect, these tiny molecular parts organize themselves in a dynamic and self-correcting manner to form precise cellular structures that may be four or five orders of magnitude larger. Understanding the proper … Continued
Developing inhibitors for metalloenzymes that ameliorate toxicity by using metal-binding groups that bind weakly to metal atoms in proteins.
The core interest of the Shan lab is to understand how biological fidelity and organization arise within the cell. Take, for example, the first few moments in a protein’s life. As a new protein emerges from the ribosome synthesizing it, numerous factors vie at the ribosome exit site to influence its folding, assembly, localization, processing, … Continued
The still largely unexplored structural and chemical diversity of natural products is unmatched by synthetic method and continues to be the most successful source for the discovery of novel scaffolds with important biological activities. We are exploiting and investigating the selectivity and specificity of the biosynthetic machineries that make these complex compounds to create ways … Continued
Integral membrane proteins regulate signal transduction and the flow of solutes and ions across cell membranes, and their disruption is involved in many human diseases. My lab focuses on the structure and dynamics of G protein-coupled receptors (GPCRs) and proteins involved in sterol and lipid homeostasis. We pioneered use of protein engineering and lipid-mediated crystallization … Continued