Muhammad Riaz, PhD, MPhil
Research & Publications
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Research Summary
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.
Coauthors
Research Interests
Cardiovascular Diseases; Stem Cells; Regenerative Medicine; Bioengineering
Public Health Interests
Cardiovascular Diseases
Selected Publications
- Signaling network model of cardiomyocyte morphological changes in familial cardiomyopathyKhalilimeybodi A, Riaz M, Campbell S, Omens J, McCulloch A, Qyang Y, Saucerman J. Signaling network model of cardiomyocyte morphological changes in familial cardiomyopathy. Journal Of Molecular And Cellular Cardiology 2022, 174: 1-14. PMID: 36370475, PMCID: PMC10230857, DOI: 10.1016/j.yjmcc.2022.10.006.
- Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic CardiomyopathyRiaz M, Park J, Sewanan LR, Ren Y, Schwan J, Das SK, Pomianowski PT, Huang Y, Ellis MW, Luo J, Liu J, Song L, Chen IP, Qiu C, Yazawa M, Tellides G, Hwa J, Young LH, Yang L, Marboe CC, Jacoby DL, Campbell SG, Qyang Y. Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy. Circulation 2022, 145: 1238-1253. PMID: 35384713, PMCID: PMC9109819, DOI: 10.1161/circulationaha.121.056265.
- Readily Available Tissue-Engineered Vascular Grafts Derived From Human Induced Pluripotent Stem CellsLuo J, Qin L, Park J, Kural MH, Huang Y, Shi X, Riaz M, Wang J, Ellis MW, Anderson CW, Yuan Y, Ren Y, Yoder MC, Tellides G, Niklason LE, Qyang Y. Readily Available Tissue-Engineered Vascular Grafts Derived From Human Induced Pluripotent Stem Cells. Circulation Research 2022, 130: 925-927. PMID: 35189711, PMCID: PMC9113663, DOI: 10.1161/circresaha.121.320315.
- Epigallocatechin gallate facilitates extracellular elastin fiber formation in induced pluripotent stem cell derived vascular smooth muscle cells for tissue engineeringEllis MW, Riaz M, Huang Y, Anderson CW, Luo J, Park J, Lopez CA, Batty LD, Gibson KH, Qyang Y. Epigallocatechin gallate facilitates extracellular elastin fiber formation in induced pluripotent stem cell derived vascular smooth muscle cells for tissue engineering. Journal Of Molecular And Cellular Cardiology 2021, 163: 167-174. PMID: 34979103, PMCID: PMC8920537, DOI: 10.1016/j.yjmcc.2021.12.014.
- Methods for Differentiating hiPSCs into Vascular Smooth Muscle CellsLi ML, Luo J, Ellis MW, Riaz M, Ajaj Y, Qyang Y. Methods for Differentiating hiPSCs into Vascular Smooth Muscle Cells. 2021, 2375: 21-34. PMID: 34591296, DOI: 10.1007/978-1-0716-1708-3_3.
- Efficient Differentiation of Human Induced Pluripotent Stem Cells into Endothelial Cells under Xenogeneic-free Conditions for Vascular Tissue EngineeringLuo J, Shi X, Lin Y, Yuan Y, Kural MH, Wang J, Ellis MW, Anderson CW, Zhang SM, Riaz M, Niklason LE, Qyang Y. Efficient Differentiation of Human Induced Pluripotent Stem Cells into Endothelial Cells under Xenogeneic-free Conditions for Vascular Tissue Engineering. Acta Biomaterialia 2020, 119: 184-196. PMID: 33166710, PMCID: PMC8133308, DOI: 10.1016/j.actbio.2020.11.007.
- Xenogeneic-free generation of vascular smooth muscle cells from human induced pluripotent stem cells for vascular tissue engineeringLuo J, Lin Y, Shi X, Li G, Kural MH, Anderson CW, Ellis MW, Riaz M, Tellides G, Niklason LE, Qyang Y. Xenogeneic-free generation of vascular smooth muscle cells from human induced pluripotent stem cells for vascular tissue engineering. Acta Biomaterialia 2020, 119: 155-168. PMID: 33130306, PMCID: PMC8168373, DOI: 10.1016/j.actbio.2020.10.042.
- Age-Associated Salivary MicroRNA Biomarkers for Oculopharyngeal Muscular Dystrophy.Raz V, Kroon RHMJM, Mei H, Riaz M, Buermans H, Lassche S, Horlings C, Swart B, Kalf J, Harish P, Vissing J, Kielbasa S, van Engelen BGM. Age-Associated Salivary MicroRNA Biomarkers for Oculopharyngeal Muscular Dystrophy. International Journal Of Molecular Sciences 2020, 21 PMID: 32842713, PMCID: PMC7503697, DOI: 10.3390/ijms21176059.
- A data-driven methodology reveals novel myofiber clusters in older human muscles.Raz Y, van den Akker EB, Roest T, Riaz M, van de Rest O, Suchiman HED, Lakenberg N, Stassen SA, van Putten M, Feskens EJM, Reinders MJT, Goeman J, Beekman M, Raz V, Slagboom PE. A data-driven methodology reveals novel myofiber clusters in older human muscles. FASEB Journal : Official Publication Of The Federation Of American Societies For Experimental Biology 2020, 34: 5525-5537. PMID: 32141137, DOI: 10.1096/fj.201902350R.
- Tissue-Engineered Vascular Grafts with Advanced Mechanical Strength from Human iPSCsLuo J, Qin L, Zhao L, Gui L, Ellis MW, Huang Y, Kural MH, Clark JA, Ono S, Wang J, Yuan Y, Zhang SM, Cong X, Li G, Riaz M, Lopez C, Hotta A, Campbell S, Tellides G, Dardik A, Niklason LE, Qyang Y. Tissue-Engineered Vascular Grafts with Advanced Mechanical Strength from Human iPSCs. Cell Stem Cell 2020, 26: 251-261.e8. PMID: 31956039, PMCID: PMC7021512, DOI: 10.1016/j.stem.2019.12.012.
- Modular design of a tissue engineered pulsatile conduit using human induced pluripotent stem cell-derived cardiomyocytesPark J, Anderson CW, Sewanan LR, Kural MH, Huang Y, Luo J, Gui L, Riaz M, Lopez CA, Ng R, Das SK, Wang J, Niklason L, Campbell SG, Qyang Y. Modular design of a tissue engineered pulsatile conduit using human induced pluripotent stem cell-derived cardiomyocytes. Acta Biomaterialia 2019, 102: 220-230. PMID: 31634626, PMCID: PMC7227659, DOI: 10.1016/j.actbio.2019.10.019.
- Patient mutations linked to arrhythmogenic cardiomyopathy enhance calpain-mediated desmoplakin degradationNg R, Manring H, Papoutsidakis N, Albertelli T, Tsai N, See CJ, Li X, Park J, Stevens TL, Bobbili PJ, Riaz M, Ren Y, Stoddard CE, Janssen PM, Bunch TJ, Hall SP, Lo YC, Jacoby DL, Qyang Y, Wright N, Ackermann MA, Campbell SG. Patient mutations linked to arrhythmogenic cardiomyopathy enhance calpain-mediated desmoplakin degradation. JCI Insight 2019, 5 PMID: 31194698, PMCID: PMC6675562, DOI: 10.1172/jci.insight.128643.
- Tissue-Engineered Stem Cell Models of Cardiovascular DiseasesAnderson C, Luo J, Sewanan L, Kural M, Riaz M, Park J, Huang Y, Niklason L, Campbell S, Qyang Y. Tissue-Engineered Stem Cell Models of Cardiovascular Diseases. 2019, 1-18. DOI: 10.1007/978-3-030-20047-3_1.
- Deacetylation Inhibition Reverses PABPN1-Dependent Muscle Wasting.Olie CS, Riaz M, Konietzny R, Charles PD, Pinto-Fernandez A, Kiełbasa SM, Aartsma-Rus A, Goeman JJ, Kessler BM, Raz V. Deacetylation Inhibition Reverses PABPN1-Dependent Muscle Wasting. IScience 2019, 12: 318-332. PMID: 30739015, PMCID: PMC6370712, DOI: 10.1016/j.isci.2019.01.024.
- Use of Human Cells and Heart Muscle Tissue Patches as Therapeutics for Heart DiseasesBatty L, Ellis M, Anderson C, Luo J, Riaz M, Park J, Das S, Huang Y, Jacoby D, Campbell S, Qyang Y. Use of Human Cells and Heart Muscle Tissue Patches as Therapeutics for Heart Diseases. 2019 DOI: 10.1016/b978-0-12-801238-3.65542-3.
- The distinct transcriptomes of slow and fast adult muscles are delineated by noncoding RNAs.Raz V, Riaz M, Tatum Z, Kielbasa SM, 't Hoen PAC. The distinct transcriptomes of slow and fast adult muscles are delineated by noncoding RNAs. FASEB Journal : Official Publication Of The Federation Of American Societies For Experimental Biology 2018, 32: 1579-1590. PMID: 29141996, DOI: 10.1096/fj.201700861R.
- Proteasomal activity-based probes mark protein homeostasis in muscles.Raz V, Raz Y, Paniagua-Soriano G, Roorda JC, Olie C, Riaz M, Florea BI. Proteasomal activity-based probes mark protein homeostasis in muscles. Journal Of Cachexia, Sarcopenia And Muscle 2017, 8: 798-807. PMID: 28675601, PMCID: PMC5659047, DOI: 10.1002/jcsm.12211.
- An alanine expanded PABPN1 causes increased utilization of intronic polyadenylation sites.Abbassi-Daloii T, Yousefi S, de Klerk E, Grossouw L, Riaz M, 't Hoen PAC, Raz V. An alanine expanded PABPN1 causes increased utilization of intronic polyadenylation sites. NPJ Aging And Mechanisms Of Disease 2017, 3: 6. PMID: 28649424, PMCID: PMC5445584, DOI: 10.1038/s41514-017-0007-x.
- Cytokine genes as potential biomarkers for muscle weakness in OPMD.Riaz M, Raz Y, van der Slujis B, Dickson G, van Engelen B, Vissing J, Raz V. Cytokine genes as potential biomarkers for muscle weakness in OPMD. Human Molecular Genetics 2016, 25: 4282-4287. PMID: 27506982, DOI: 10.1093/hmg/ddw259.
- PABPN1-Dependent mRNA Processing Induces Muscle Wasting.Riaz M, Raz Y, van Putten M, Paniagua-Soriano G, Krom YD, Florea BI, Raz V. PABPN1-Dependent mRNA Processing Induces Muscle Wasting. PLoS Genetics 2016, 12: e1006031. PMID: 27152426, PMCID: PMC4859507, DOI: 10.1371/journal.pgen.1006031.
- Differential myofiber-type transduction preference of adeno-associated virus serotypes 6 and 9.Riaz M, Raz Y, Moloney EB, van Putten M, Krom YD, van der Maarel SM, Verhaagen J, Raz V. Differential myofiber-type transduction preference of adeno-associated virus serotypes 6 and 9. Skeletal Muscle 2015, 5: 37. PMID: 26561520, PMCID: PMC4641337, DOI: 10.1186/s13395-015-0064-4.
- Growth and metastatic behavior of molecularly well-characterized human breast cancer cell lines in mice.Riaz M, Setyono-Han B, Timmermans MA, Trapman AM, Bolt-de Vries J, Hollestelle A, Janssens RC, Look MP, Schutte M, Foekens JA, Martens JW. Growth and metastatic behavior of molecularly well-characterized human breast cancer cell lines in mice. Breast Cancer Research And Treatment 2014, 148: 19-31. PMID: 25266129, DOI: 10.1007/s10549-014-3142-0.
- miRNA expression profiling of 51 human breast cancer cell lines reveals subtype and driver mutation-specific miRNAs.Riaz M, van Jaarsveld MT, Hollestelle A, Prager-van der Smissen WJ, Heine AA, Boersma AW, Liu J, Helmijr J, Ozturk B, Smid M, Wiemer EA, Foekens JA, Martens JW. miRNA expression profiling of 51 human breast cancer cell lines reveals subtype and driver mutation-specific miRNAs. Breast Cancer Research : BCR 2013, 15: R33. PMID: 23601657, PMCID: PMC3672661, DOI: 10.1186/bcr3415.
- High TWIST1 mRNA expression is associated with poor prognosis in lymph node-negative and estrogen receptor-positive human breast cancer and is co-expressed with stromal as well as ECM related genes.Riaz M, Sieuwerts AM, Look MP, Timmermans MA, Smid M, Foekens JA, Martens JW. High TWIST1 mRNA expression is associated with poor prognosis in lymph node-negative and estrogen receptor-positive human breast cancer and is co-expressed with stromal as well as ECM related genes. Breast Cancer Research : BCR 2012, 14: R123. PMID: 22967435, PMCID: PMC4053101, DOI: 10.1186/bcr3317.
- Correlation of breast cancer susceptibility loci with patient characteristics, metastasis-free survival, and mRNA expression of the nearest genes.Riaz M, Berns EM, Sieuwerts AM, Ruigrok-Ritstier K, de Weerd V, Groenewoud A, Uitterlinden AG, Look MP, Klijn JG, Sleijfer S, Foekens JA, Martens JW. Correlation of breast cancer susceptibility loci with patient characteristics, metastasis-free survival, and mRNA expression of the nearest genes. Breast Cancer Research And Treatment 2012, 133: 843-51. PMID: 21748294, DOI: 10.1007/s10549-011-1663-3.
- Association of rare MSH6 variants with familial breast cancer.Wasielewski M, Riaz M, Vermeulen J, van den Ouweland A, Labrijn-Marks I, Olmer R, van der Spaa L, Klijn JG, Meijers-Heijboer H, Dooijes D, Schutte M. Association of rare MSH6 variants with familial breast cancer. Breast Cancer Research And Treatment 2010, 123: 315-20. PMID: 19924528, DOI: 10.1007/s10549-009-0634-4.
- Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines.Hollestelle A, Nagel JH, Smid M, Lam S, Elstrodt F, Wasielewski M, Ng SS, French PJ, Peeters JK, Rozendaal MJ, Riaz M, Koopman DG, Ten Hagen TL, de Leeuw BH, Zwarthoff EC, Teunisse A, van der Spek PJ, Klijn JG, Dinjens WN, Ethier SP, Clevers H, Jochemsen AG, den Bakker MA, Foekens JA, Martens JW, Schutte M. Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines. Breast Cancer Research And Treatment 2010, 121: 53-64. PMID: 19593635, DOI: 10.1007/s10549-009-0460-8.
- Low-risk susceptibility alleles in 40 human breast cancer cell lines.Riaz M, Elstrodt F, Hollestelle A, Dehghan A, Klijn JG, Schutte M. Low-risk susceptibility alleles in 40 human breast cancer cell lines. BMC Cancer 2009, 9: 236. PMID: 19607694, PMCID: PMC3087328, DOI: 10.1186/1471-2407-9-236.