Labs

Synaptic Transmission | Neurotransmitter Release | Fragile X Syndrome | FMRP | Autism | GABAergic Inhibition | Neural Circuits | Super Resolution Microscopy | Electrophysiology | Modeling

The goal of our research program is to develop and apply nanoscale resolution approaches to understand the fundamental mechanisms of synaptic transmission in central synapses under normal conditions, and how disruptions in synaptic functions lead to disease states, particularly Fragile X syndrome and Alzheimer’s disease.

The focus of Lishko lab is on dissecting the role of bioelectricity in reproduction, aging, and metabolism. We are developing and applying advanced biophysical, biochemical, and cell biology methods to study how mammalian tissues and cells are regulated by unconventional steroid signaling and play a role in mammalian reproduction and neuronal functions. Specifically, our team studies the role of steroid-modulated ion channels in age-related macular degeneration, neurodegeneration, ovarian aging, and fertility. We also work on developing small-molecule-based therapies to treat reproductive and age-related disorders.

Signal Transduction | Mass Spectrometry | Integrative OMICs | Cancer | Clinical Proteomics | Kinases

We study how alterations in signal transduction leads to human disease.  We start with a “systems level” integrative discovery platform, one that has as a foundation mass spectrometry-based proteomics. Chemical and genetic functional screens enrich the proteomic metworks to yield disease-annotated physical/functional maps for signaling pathways of interest. The models and hypotheses produced are challenged through mechanistic and phenotypic studies employing cultured human cells in 2D and 3D, mouse models, clinical samples and in vitro biochemical systems. We have longstanding interest in the Wnt pathway and the KEAP1/NRF2 oxidative stress response pathway, as well as kinases and ubiquitin ligases.

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.

Mitochondrial Metabolism | Protein Biochemistry | Chemical Biology | Systems Genetics | Rare Diseases

Mitochondria are complex and dynamic organelles that are home to a vast array of essential metabolic pathways and processes and whose dysfunction underlies hundreds of human diseases. Despite this, much of the basic biology of these organelles remains obscure, and therapeutic options to treat mitochondrial dysfunction remain woefully inadequate. By blending classic biochemistry, molecular & cellular biology, and genetics with large-scale proteomics and systems approaches, our lab aims to systematically define the functions of uncharacterized mitochondrial proteins, identify new gene mutations that underlie human disease, and explore new molecular therapeutics to rectify mitochondria-based disorders.

Fluorescence | Imaging | Quantitative Biology | Mathematical Models

Our lab focuses on understanding glucose-regulated hormone secretion from the islet of Langerhans, which is made up of glucagon secreting α-cells, insulin-secreting β-cells, and somatostatin-secreting δ-cells.  Recent work has uncovered glucagon’s critical role in glucose homeostasis and the pathology of diabetes.  Multiple signaling pathways arising from intrinsic glucose sensing, paracrine interactions and juxtacrine contacts within the islet all play a role in α-cell function.  Our lab develops quantitative fluorescence technology broadly applicable to cell, tissue, and whole-organism imaging experiments.  We apply these methods to assay living islet function quantitatively both ex vivo and in vivo, and these studies are proving critical to advancing our understanding of the regulation of glucagon secretion from α-cells.

Senescence | Cancer | Immunotherapy | Therapy-induced Comorbidities | Age-related Cancer Drivers

Age remains the largest risk factor for the development of cancer, begging the question, what about aging drives the rapid increase in cancer we see in the 5th to 6th decade of life? While the answer is complicated, the Stewart laboratory focuses on how age-related changes in the tumor microenvironment contribute to tumor progression. This work includes delving into the mechanisms that drive senescence and secretion of pro-tumorigenic senescence associated secretory phenotype (SASP) factors. In addition, given senescent stromal cells recapitulate the phenotypes of cancer associated fibroblasts (CAFs), the laboratory also studies these important cells in both the primary and metastatic setting.

Vascular Development | Cardiovascular Disease | Mechanobiology | Biophysical Regulation of Transcript/Gene Expression | Zebrafish | Live Time-Lapse Imaging | CRISPR Mutagenesis | Cell Signaling | Tissue Patterning | In Vitro Modeling

The Stratman lab studies signaling pathways regulating vascular development using zebrafish as a model system. Our ongoing research aims to understand how biomechanical forces, such as changes in tissue microenvironment or blood flow state, affect vascular patterning, signaling, and stabilization. Current lab projects focus on 1) the role of vascular primary cilia as mechanosensors, 2) the role of mechanical sensitive ion channels in regulating vascular stabilization, and 3) the role of endocytic trafficking and EVs in communication between the vasculature and the microenvironment.

The True Lab is interested in the biological consequences of yeast prions - in both their capacity to function as novel epigenetic elements, as well as in their utility in modeling mechanisms of protein misfolding and aggregation that mimic important events in several neurodegenerative disorders. Additionally, we are interested in how prions in yeast impact survival and adaptation. We are also interested in understanding what other prions exist and how broadly prions affect cellular physiology. We are also using yeast prions to understand how the environment influences protein misfolding and aggregation, a question that has been difficult to address with current model systems of neurodegenerative disorders.