Harvard Catalyst Profiles

This is an extension of an American Heart Association Strategically Focused Research Network (SFRN) on Cardiometabolic disease. The PI, Mark W. Feinberg, MD, is Co-Director of the Center at BWH. The Basic Project involves the discovery and characterization of novel non-coding RNAs, both miRNAs and long non-coding RNAs (lncRNAs) using diabetic mouse models in: 1) the progression and regression phases of atherosclerosis; and 2) myocardial infarction. Key observations will be validated using cellular assays and functional studies in mouse models of vascular disease. The projects would be a great opportunity for a medical student for up to 3-12 months and would provide a framework for acquiring knowledge and skills of RNA-Seq/miRNA-Seq/single cell RNA seq biology, molecular & cell biology, functional assays (ie. cell adhesion, migration, differentiation, others), and/or analyses of diseased mice depending upon the project. We utilize RNA-based therapeutics to target specific non-coding RNAs in vivo. The Feinberg Laboratory is located in the Center for Excellence in Vascular Biology at the New Research Building (NRB/ Harvard Institutes of Medicine). Lab meetings and seminars are held virtually. These projects are in various levels of maturity and I would be happy to discuss them to any HMS/HSDM students interested in learning more.

We have several research projects involving either microRNAs or lncRNAs identified in specific cell types important in cardiovascular diseases such as atherosclerosis, myocardial infarction, and limb ischemia. Studies are examining these non-coding RNAs from mice to human samples and focus on evolutionarily conserved ncRNAs and their targets. Related projects available involve expression, functional, and mechanistic studies of such factors in a given cell type such as monocyte/macrophages, T cells (T regulatory cells), or endothelial cells. For microRNAs identified, validation studies would also include using available databases and bioinformatics to verify gene targets and binding to 3’-UTR regions. For lncRNAs, both cis and trans-regulated mechanisms are pursued. Key observations will be validated using functional assays in mouse models of vascular disease. The projects would be a great opportunity for a medical student for 3-12 months and would provide a framework for acquiring knowledge and skills of RNA-Seq/miRNA-Seq biology, molecular & cell biology, functional assays (ie. cell adhesion, migration, differentiation, others), and/or analyses of diseased mice depending upon the project. The setting would include laboratory meetings at the Center for Excellence in Vascular Biology at the New Research Building (NRB/ Harvard Institutes of Medicine) as well as weekly divisional meetings. These projects are in various levels of maturity and I would be happy to discuss them to any HMS/HSDM students interested in learning more.

We have generated a unique heart failure with preserved ejection failure (HFpEF) model across males, females, and ovariectomized female mice which will provide a unique opportunity to learn about the role of non-coding RNAs and their targets in the pathogenesis of cardiovascular disease and sex-associated differences. We have several -omics datasets (single cell RNA-seq / RNA-seq / ATAC-seq) and top targets can be explored in cell-based assays or expression in tissue samples. The student would be involved in a focused aspect of the project depending on time commitment.

We have identified a smooth muscle cell specific long non-coding RNA (lncRNA) that is evolutionary conserved from mice to human subjects. We use genetic KO mice and inhibitors to the lncRNA to uncover its role in mouse models of atherosclerosis, hypertension, and vascular remodeling. Mechanistic studies are also being explored to understand how this lncRNA regulates SMC biology in cell-based assays utilizing a combination of RNA pulldowns, siRNA knockdown, or isolation of KO SMCs from mice. Depending on time commitment, a focused aspect of this project can help illuminate its role in cardiovascular disease from mice to human samples.