_RESEARCH
PROJECTS & THEMES
Multiorgan pathophysiology of COVID-19
Studies in our laboratory have shown that SARS-CoV2 infection results in direct damage to human cardiomyocytes and this damage is exacerbated by cytokines. We are using cellular mechanism-based approaches, including single cell transcriptomic experiments, to identify the changes in pathways in human iPSC derived cardiomyocytes that can lead to clinical pathophysiology. Integrating this with clinical data allows us to potentially identify genomic predictors for myocarditis susceptibility.
Primary Investigator
Ravi Iyengar, PhD
Computational Models of Whole Cell Function
We are developing predictive scalable models of whole cell functions, explaining them in terms of cellular components and their interactions arranged as pathways and networks. By identifying regulatory motifs like feedback and feedforward loops, we aim to understand and predict variability in whole cell responses. Current models utilize spatially resolved single cell RNA-Seq and focus on systems like cannabinoid-1 receptor-regulated neurite outgrowth.
Primary Investigator
Ravi Iyengar, PhD
Forgetting
For over two decades we have studied how interactions among cell signaling networks within neurons regulate neuronal plasticity. We found that memory formation processes activate transcriptional repressors like WT1 that enable forgetting. We are now studying the relationships between molecular pathways and cellular circuits within the hippocampus involved in forgetting and memory interference.
Primary Investigator
Ravi Iyengar, PhD
Cell Shape and Tissue Organization
Cell shape is a distinct locus of retrievable information separate from biochemical signals. We investigate how shape and spatial organization within and between cells contributes to the dynamic stability of tissue-level physiology. Using biochips and integrated computational modeling (including neural networks and PDEs), we decipher how cellular morphology regulates tissue integrity and physiological function.
Primary Investigator
Ravi Iyengar, PhD
Kidney Precision Medicine Project - The Kidney Atlas
As part of the Central Hub of the Kidney Precision Medicine Project, we are developing a comprehensive kidney atlas that integrates morphology with molecular components. We computationally analyze different types of omics data to map pathways and networks in various renal cell types across disease states, aiming to improve molecular diagnosis and drug discovery for kidney disease.
Primary Investigator
Ravi Iyengar, PhD
Systems Pharmacology
We develop systems-level approaches to understanding drug action at a genome-wide level. This includes predictive toxicology, aimed at predicting drug-induced adverse events based on the human genome, and developing mechanism-based drug combinations for complex diseases by mapping the cellular networks underlying drug action.
Primary Investigator
Ravi Iyengar, PhD
Cardiotoxicity of Targeted Cancer Therapeutics
Many cancer therapeutics produce serious side effects like heart failure. We utilize large-scale protein-protein interaction networks and transcriptomic signatures from iPSC-derived cardiomyocytes to predict these adverse events. By mining FDA reporting databases (FAERS), we identify drug combinations that can mitigate toxicity and explain rare adverse event reports through network-based prediction algorithms.
Primary Investigator
Ravi Iyengar, PhD
Drugs for Aneurysms
Collaborating with experts in thoracic aneurysms and Marfan syndrome, we use transcriptomic data to identify common networks across human and animal models. This has led to the identification of baclofen as a potential therapeutic to mitigate aneurysm progression. We continue to use mechanism-based approaches to identify control points for the mechanical properties of the vessel wall.
Primary Investigator
Ravi Iyengar, PhD
Drugs for Neurorepair
Computational modeling of neurite outgrowth has enabled the identification of multiple drugs that promote the regeneration of severed axons. In vivo tests using optic nerve crush models have demonstrated functional nerve regeneration and light-driven electrophysiological signals. Ongoing experiments focus on improving temporal dynamics and testing combinations for spinal cord injury repair.
Primary Investigator
Ravi Iyengar, PhD
