Cell Biology & Physiology

The Chen Lab's research focuses on a unique class of RNA - circular RNA (circRNA), with the aim of uncovering circRNAs' regulatory and functional roles, as well as their clinical implications. By utilizing innovative multi-omic and high-throughput screening approaches to identify the genomic elements, RNA structures, and protein components that regulate circRNA functions, we strive to advance our understanding of circRNA's biological significance and disease relevance. Our long-term goal is to develop circRNAs as a novel RNA therapeutic platform, revolutionizing next-generation RNA technology and therapeutics.

Research keywords: RNA; Translation; Stress

Learn more

The Crewe lab uses transgenic mouse lines, cell culture and biochemistry to understand extracellular vesicle (EV)-mediated signaling during homeostatic and pathologic metabolic regulation. We are focused on understanding this in the context of obesity and type 2 diabetes with a particular emphasis on adipocyte-derived EVs. We are particularly excited about a subpopulation of EVs from adipocytes carry damaged mitochondria which are transferred to other organs.

Research keywords: extracellular vesicles; metabolism; Obesity

Learn more

We investigate the mechanisms of non-alcoholic fatty liver disease (NAFLD) with a focus on mitochondria and autophagy. We also seek to develop new therapeutic strategies to reduce hepatic injury after liver resection and transplant of fatty livers. Our study models include mice, rats, and human livers. Our study has potentials to 1) develop therapeutic strategies to reduce fatty liver disease and 2) expand donor liver pool. Currently, fatty donor livers are discarded without transplant.

Research keywords: liver; mitochondria; autophagy

Learn more

Our research focuses on the mechanisms of synaptic transmission. We utilize cutting-edge multi-color super-resolution imaging tools to examine synaptic function and dysfunction in the brain at molecular, cellular and circuit levels. Our major current directions are to understand how neurotransmitter release is organized and regulated in individual central synapses, and to link dysregulation in synaptic and cellular processes with the circuit and ultimately behavioral impairments observed in autism and Fragile X syndrome. We have recently expanded our interests towards elucidating the role of glia in modulating synaptic function and plasticity.

Research keywords: synaptic transmission; super-resolution microscopy; glia

Learn more

We use mass spectrometry-based proteomics to study signal transduction in disease, with a focus on the NRF2 pathway and 'dark' kinases. Ongoing projects include the cryoEM structure of KEAP1/NRF2, cell biology of KEAP1 mutations and biomolecular condensates, and small molecule screens for NRF2 inhibitors, including novel compounds that block one-carbon metabolism. We also study NRF2 in new mouse models of cancer and across clinical tumor biopsies using targeted proteomics. We lead a new clinical trial for a NRF2 inhibitor in head and neck cancer. Understudied kinases are being illuminated through large scale promiscuous biotin proximity proteomics and computational scoring.

Research keywords: proteomics; cancer; signal transduction

Learn more

We aim to uncover the design principles governing the organization of the eukaryotic cell using a combination of quantitative microscopy, single cell transcriptomics, metabolomics, and mathematical modeling.

Research keywords: quantitative cell biology; biophysics; organelles

Learn more

Research in my laboratory is focused on the biology of ion channels.
We develop, introduce and use a wide range of molecular biological and biophysical approaches, as well as in vivo gene manipulation to address questions in proteins, cells and animals, and now in humans. These efforts are leading us to detailed understanding of both molecular mechanisms of channel activity, and roles of ion channels in multiple disease processes including diabetes, heart failure, pulmonary disease and epilepsy.

Research keywords: Ion channels; Excitability; Disease

Learn more

We aim to understand how age-related changes in the tumor microenvironment impact tumorigenesis. We’ve shown that aged stromal cells, similar to cancer associated fibroblasts, express p38MAPK/MK2-dependent pro-tumorigenic factors and we’ve developed murine models to explore the role senescent stromal cells play in the preneoplastic and premetastatic niches. Through this work we’ve focused on how inhibition of the p38/MK2 pathway can make metastatic disease susceptible to immunotherapy. More recently, we’ve begun to explore how some of these same changes contribute to therapy-induced comorbidities. The laboratory also examines how age-related changes in the premetastatic niche facilitate tumor cell seeding, dormancy and outgrowth.

Research keywords: senescence; breast cancer; metastasis

Learn more