Browsing by Author "Arzaghi, Hamidreza"

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    Engineered human iPS cell models reveal altered podocytogenesis and glomerular capillary wall in CHD-associated SMAD2 mutations.
    (bioRxiv, 2024-08-06) Bhattacharya, Rohan; Ward, Tarsha; Kalejaiye, Titilola D; Mishra, Alekshyander; Leeman, Sophia; Arzaghi, Hamidreza; Seidman, Jonathan G; Seidman, Christine E; Musah, Samira
    Early developmental programming involves extensive cell lineage diversification through shared molecular signaling networks. Clinical observations of congenital heart disease (CHD) patients carrying SMAD2 genetic variants revealed correlations with multi-organ impairments at the developmental and functional levels. For example, many CHD patients present with glomerulosclerosis, periglomerular fibrosis, and albuminuria. Still, it remains largely unknown whether SMAD2 variants associated with CHD can directly alter kidney cell fate, tissue patterning, and organ-level function. To address this question, we engineered human iPS cells (iPSCs) and organ-on-a-chip systems to uncover the role of pathogenic SMAD2 variants in kidney podocytogenesis. Our results show that abrogation of SMAD2 causes altered patterning of the mesoderm and intermediate mesoderm (IM) cell lineages, which give rise to nearly all kidney cell types. Upon further differentiation of IM cells, the mutant podocytes failed to develop arborizations and interdigitations. A reconstituted glomerulus-on-a-chip platform exhibited significant proteinuria as clinically observed in glomerulopathies. This study implicates CHD-associated SMAD2 mutations in kidney tissue malformation and provides opportunities for therapeutic discovery in the future.
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    Epigenetics of Hypertensive Nephropathy.
    (Biomedicines, 2024-11) Zhang, Yize; Arzaghi, Hamidreza; Ma, Zhehan; Roye, Yasmin; Musah, Samira
    Hypertensive nephropathy (HN) is a leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD), contributing to significant morbidity, mortality, and rising healthcare costs. In this review article, we explore the role of epigenetic mechanisms in HN progression and their potential therapeutic implications. We begin by examining key epigenetic modifications-DNA methylation, histone modifications, and non-coding RNAs-observed in kidney disease. Next, we discuss the underlying pathophysiology of HN and highlight current in vitro and in vivo models used to study the condition. Finally, we compare various types of HN-induced renal injury and their associated epigenetic mechanisms with those observed in other kidney injury models, drawing inferences on potential epigenetic therapies for HN. The information gathered in this work indicate that epigenetic mechanisms can drive the progression of HN by regulating key molecular signaling pathways involved in renal damage and fibrosis. The limitations of Renin-Angiotensin-Aldosterone System (RAAS) inhibitors underscore the need for alternative treatments targeting epigenetic pathways. This review emphasizes the importance of further research into the epigenetic regulation of HN to develop more effective therapies and preventive strategies. Identifying novel epigenetic markers could provide new therapeutic opportunities for managing CKD and reducing the burden of ESRD.
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    Unleashing the power of biomaterials to enhance organoid differentiation and function.
    (Nature methods, 2024-09) Musah, Samira; Arzaghi, Hamidreza
    Biomaterials are revolutionizing organoid development by offering tunable platforms that provide instructive cues, which enhance cell fate transitions, tissue-level functions and reproducibility. These advances are crucial for harnessing the translational potential of organoids.