Research & Publications
Over the years, I have acquired numerous cutting-edge cell biology, molecular biology, and genomics skills including drug screening, tissue-specific therapeutic gene delivery, and genome editing techniques such as TALEN and CRISPR-cas9 to create desired changes in the genome for the discovery of therapeutic targets for the patient cure in cardiovascular diseases in particular and tissue repair and regeneration in general. Towards this end, I have developed multiple (clinical grade) immunoevasive universal iPSCs as a bioresource that can readily provide a limitless number of immunocompatible, terminally differentiated functional cells to support cardiovascular tissue defects and organ repair and regeneration. The development of human universal cardiovascular tissues is anticipated to offer a solution to immune rejection in allogeneic transplantation, thereby allowing universal derivative cells to be suitable for any patient as an “off-the-shelf” cell source, dramatically saving time and cost of production and treatment and presenting a revolutionary new paradigm for the effective and safe clinical treatment of cardiovascular diseases. I have supervised multiple students at various levels of their educational careers and successfully interacted with colleagues locally and internationally to foster new collaborations.
Extensive Research Description
I am investigating biomechanical signaling and molecular mechanisms underlying cardiomyopathies including hypertrophic cardiomyopathy and amyloid cardiomyopathy (ACM). My research group routinely generates iPSCs from the peripheral blood mononuclear cells (PBMCs) of healthy individuals and patients via Sendai virus-based over-expression of Yamanaka transcription factors. This is coupled with the generation of isogenic iPSCs as control using genome editing technologies. Such patient-specific iPSCs and their corresponding isogenic controls are differentiated into functional cardiomyocytes (iPSC-CMs) for disease modeling. Using such patient-specific iPSC-CMs and through comprehensive multi-model integrative approaches including culturing patient-specific iPSC-CMs in a 2-dimensional monolayer culture system or seeding them into a decellularized scaffold of pig myocardium to construct 3-dimensional engineered heart tissue (EHTs) coupled with computational modeling, I have uncovered new mechano-transduction signaling pathway operative in heart conditions (Riaz et al Circulation 2022). Moreover, I am involved in establishing the foundation for developing innovative mechanism-based treatments for cardiovascular diseases (Ng et al JCI Insight. 2019, Park et al Acta Biomater. 2020; Luo et al Cell Stem Cell 2020; Ellis et al, J Mol Cell Cardiol. 2021; Lou et al Circulation Research 2022).
Recently, I established a genome editing facility in Qyang’s laboratory at the Yale Cardiovascular Research Center. In this facility, the clustered regularly interspaced short palindromic repeat-cas9 (CRISPR-Cas9) and the transcription activator-like effector-nuclease (TALEN) techniques are being applied to sknock in/out genetic mutations in normal or in patient-specific iPSCs to establish causal relations of the mutations with cardiovascular muscle functions (Riaz et al Circulation 2022). One of many emerging focuses of this facility is to create immunoevasive universal iPSCs for cardiovascular tissue repair and regeneration in allogeneic settings. In collaboration with Professor Al Sinusas's group at Yale University School of Medicine, I am also pursuing the regenerative potential of the iPSC-derived ISL1+ cardiovascular progenitors for ischemic heart repair in small (mouse/rat) and large (pig) preclinical models. These efforts focus on understanding the molecular basis for myocardial ischemia, angiogenesis, arteriogenesis, atrial and ventricular remodeling, and peripheral artery disease using multi-modality imaging techniques.
Cardiovascular Diseases; Stem Cells; Regenerative Medicine; Bioengineering
Public Health Interests