Erika Wang

• Doctor of Philosophy
• Postdoc Fellow- Langer Lab at Massachusetts Institute of Technology

Myocardial fibrosis is a severe global health problem due to its prevalence in all forms of cardiac diseases and direct role in causing heart failure. The discovery of efficient antifibrotic compounds has been hampered due to the lack of a physiologically relevant disease model. Herein, we present a disease model of human myocardial fibrosis and us...

Study of the molecular basis of myocardial fibrosis is hampered by limited access to tissues from human patients and by confounding variables associated with sample accessibility, collection, processing and storage. Here, we report an integrative strategy based on mass spectrometry for the phosphoproteomic profiling of normal and fibrotic cardiac t...

Vaccines provide substantial safety against infectious diseases, saving millions of lives each year. The recent COVID-19 pandemic highlighted the importance of vaccination in providing mass-scale immunization against outbreaks. However, the delivery of vaccines imposes a unique set of challenges due to their large molecular size and low room temper...

Medical interventions often require timed series of doses, thus necessitating accurate medical record-keeping. In many global settings, these records are unreliable or unavailable at the point of care, leading to less effective treatments or disease prevention. Here we present an invisible-to-the-naked-eye on-patient medical record-keeping technolo...

Link for download https://rdcu.be/dIO17

Pathogenic variants in MYH7 and MYBPC3 account for the majority of hypertrophic cardiomyopathy (HCM). Targeted drugs like myosin ATPase inhibitors have not been evaluated in children. We generate patient and variant-corrected iPSC-cardiomyocytes (CMs) from pediatric HCM patients harboring single variants in MYH7 (V606M; R453C), MYBPC3 (G148R) or di...

Nanomaterials offer unique opportunities to engineer immunomodulatory activity. In this work, we report the Toll-like receptor agonist activity of a nanoscale adjuvant zeolitic imidazolate framework–8 (ZIF-8). The accumulation of ZIF-8 in endosomes and the pH-responsive release of its subunits enable selective engagement with endosomal Toll-like re...

The successful translation of organ-on-a-chip devices requires the development of an automated workflow for device fabrication, which is challenged by the need for precise deposition of multiple classes of materials in micro-meter scaled configurations. Many current heart-on-a-chip devices are produced manually, requiring the expertise and dexterit...

Recent advances in both cardiac tissue engineering and hearts‐on‐a‐chip are grounded in new biomaterial development as well as the employment of innovative fabrication techniques that enable precise control of the mechanical, electrical, and structural properties of the cardiac tissues being modelled. The elongated structure of cardiomyocytes requi...

To better understand sodium channel (SCN5A)-related cardiomyopathies, we generated ventricular cardiomyocytes from induced pluripotent stem cells obtained from a dilated cardiomyopathy patient harbouring the R222Q mutation, which is only expressed in adult SCN5A isoforms. Because the adult SCN5A isoform was poorly expressed, without functional diff...

Hypertrophic cardiomyopathy (HCM) is mainly caused by sarcomere gene variants in MYH7 and MYBPC3. Targeted drugs like myosin ATPase inhibitors have shown efficacy in adult HCM but have not been evaluated in children. We generated iPSC-cardiomyocytes (CMs) from four children with HCM harboring variants in MYH7 ( V606M; R453C) or MYBPC3 (G148R; P955f...

We review the emergence of the new field of organ-on-a-chip (OOAC) engineering, from the parent fields of tissue engineering and microfluidics. We place into perspective the tools and capabilities brought into the OOAC field by early tissue engineers and microfluidics experts. Liver-on-a-chip and heart-on-a-chip are used as two case studies of syst...

Human fibrotic diseases constitute a major health problem worldwide. Fibrosis involves significant etiological heterogeneity and encompasses a wide spectrum of diseases affecting various organs. To date, many fibrosis targeted therapeutic agents failed due to inadequate efficacy and poor prognosis. In order to dissect disease mechanisms and develop...

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold tremendous promise for in vitro modeling to assess native myocardial function and disease mechanisms as well as testing drug safety and efficacy. However, current iPSC- CMs are functionally immature, resembling in vivo CMs of fetal or neonatal developmental states. The use of targ...

Extensive progress has been made in developing engineered models for elucidating human cardiac disease. Cardiac fibrosis is often associated with all forms of cardiac disease and has a direct deleterious effect on cardiac function. As currently there is no effective therapeutic strategy specifically designed to target fibrosis, in vitro diagnostic...

Angiotensin II (Ang II) presents a critical mediator in various pathological conditions such as non-genetic cardiomyopathy. Osmotic pump infusion in rodents is a commonly used approach to model cardiomyopathy associated with Ang II. However, profound differences in electrophysiology and pharmacokinetics between rodent and human cardiomyocytes may l...

Owing to their high spatiotemporal precision and adaptability to different host cells, organ-on-a-chip systems are showing great promise in drug discovery, developmental biology studies and disease modeling. However, many current micro-engineered biomimetic systems are limited in technological application because of culture media mixing that does n...

Accumulating evidence indicates that air pollution contributes to serious and fatal damage to the cardiovascular system, yet the mechanisms that drive air pollution associated cardiovascular disease and dysfunction remain unclear. In an effort to create a more predictive in vitro model, a 3D platform, known as integrated vasculature for assessing d...

Tumor progression relies on the interaction between neoplastic epithelial cells and their surrounding stromal partners. This cell cross‐talk affects stromal development, and ultimately the heterogeneity impacts drug efficacy. To mimic this evolving paradigm, 3D vascularized pancreatic adenocarcinoma tissue is microengineered in a tri‐culture system...

Modeling of human organs has long been a task for scientists in order to lower the costs of therapeutic development and understand the pathological onset of human disease. For decades, despite marked differences in genetics and etiology, animal models remained the norm for drug discovery and disease modeling. Innovative biofabrication techniques ha...

Organ-on-a-chip systems have the potential to revolutionize drug screening and disease modeling through the use of human stem cell-derived cardiomyocytes. The predictive power of these tissue models critically depends on the functional assembly and maturation of human cells that are used as building blocks for organ-on-a-chip systems. To resemble a...

In article number 1801187 by Milica Radisic, Boyang Zhang, and co‐workers, a scalable, functional, and 96‐well plate compatible platform is presented with innovative multimaterial processing. Three classes of materials are integrated, including built‐in electrodes to drive electrical stimulation for tissue maturation and induce tissue contraction d...

Tissue engineering using cardiomyocytes derived from human pluripotent stem cells holds a promise to revolutionize drug discovery, but only if limitations related to cardiac chamber specification and platform versatility can be overcome. We describe here a scalable tissue-cultivation platform that is cell source agnostic and enables drug testing un...

Due to escalating drug developmental costs and limitations of cardiotoxicity screening, there is an urgent need to develop robust in vitro 3D tissue culture platforms that can both facilitate the culture of human cardiac tissues and provide noninvasive functional readouts predictive of cardiotoxicity in clinical settings. However, such platforms co...

Cardiovascular disease is the leading cause of death worldwide. Although investment in drug discovery and development has been sky-rocketing, the number of approved drugs has been declining. Cardiovascular toxicity due to therapeutic drug use claims the highest incidence and severity of adverse drug reactions in late-stage clinical development. The...

Significant advances in biomaterials, stem cell biology, and microscale technologies have enabled the fabrication of biologically relevant tissues and organs. Such tissues and organs, referred to as organ-on-a-chip (OOC) platforms, have emerged as a powerful tool in tissue analysis and disease modeling for biological and pharmacological application...

Engineering functional cardiac tissues remains an ongoing significant challenge due to the complexity of the native environment. However, our growing understanding of key parameters of the in vivo cardiac microenvironment and our ability to replicate those parameters in vitro are resulting in the development of increasingly sophisticated models of...

Drug discovery and development continues to be a challenge to the pharmaceutical industry despite great advances in cell and molecular biology that allow for the design of better targeted therapeutics. Many potential drug compounds fail during the clinical trial due to inefficacy and toxicity that were not predicted during preclinical stages. The f...

Myocardial ischemia and angiotensin II activate the tumor suppressor p53 protein, which promotes cell death. Previously, we showed that the Bcl-2 death gene Bnip3 is highly induced during ischemia, where it triggers mitochondrial perturbations resulting in autophagy and cell death. However, whether p53 regulates Bnip3 and autophagy is unknown. Here...

Background: TNFα and other pro-inflammatory cytokines activate the canonical NF-kB pathway through the IkBa kinase (IKK) signaling complex. IKKβ kinase is also critical for Akt-mediated NF-κB activation in ventricular myocytes. Akt activates the kinase (mechanistic target of rapamycin (mTOR), which mediates important processes such as metabolism pr...

Myocardial ischemia and angiotensin II activate the tumor suppressor p53 protein, which promotes cell death. Previously, we showed that the Bcl-2 death gene Bnip3 is highly induced during ischemia, where it triggers mitochondrial perturbations resulting in autophagy and cell death. However, whether p53 regulates Bnip3 and autophagy is unknown. Here...

Background: Tumor necrosis factor-α and other proinflammatory cytokines activate the canonical nuclear factor (NF)-κB pathway through the kinase IKKβ. Previously, we established that IKKβ is also critical for Akt-mediated NF-κB activation in ventricular myocytes. Akt activates the kinase mammalian target of rapamycin (mTOR), which mediates importa...

Alternative gene splicing provides a versatile mechanism by which cells generate proteins with different or even antagonistic properties. Previously we determined the hypoxia-inducible protein Bnip3 is integral component of the mitochondrial death pathway that can signal apoptosis and autophagy but the precise mechanisms that differentially regulat...

Autophagy constitutes a catabolic process involving lysosomal degradation of damaged and redundant cytosolic components into biomolecules, via an elaborate lysosomal pathway. Autophagy is a highly regulated and evolutionary conserved process crucial for normal tissue homeostasis and cell life. Certain members of the Bcl-2 gene family, including the...

Autophagy is an evolutionary conserved process that allows cells to recycle or discard macromolecular constituents or damaged organelles during times of metabolic crisis. Alternative mRNA splicing is a versatile mechanism by which cells generate proteins with different or even antagonistic properties. Herein, we show that inclusion or skipping of e...

Recent animal studies suggest that programmed necrosis plays a critical role in ischemia/reperfusion induced cardiac cell death and in the progression to heart failure. This caspase-independent form of programmed cell death involves RIP1/RIP3 phosphorylation and activation, as well as the formation of the cyclophilin D (CypD)-dependent mitochondria...

A delicate balance exists between cell growth and cell death. In the context of the adult myocardium, inappropriate or inordinate cell loss through an apoptotic process may profoundly influence cardiac structure, function, or both given the limited and meager ability of the heart for repair after injury. Earlier work by the authors' laboratory iden...