Asmaa S Abu maziad

Interests

Teaching

I like to teach students and residents in an easy and clear way. I like to be creative and apply methods that the learner can save info for longer time.

Research

Basic research is my primary interest. I am trying to improve myself in all aspects of basic research including bench work and grant writing.

Courses

Scholarly Contributions

Journals/Publications

• Pitsillou, E., Logothetis, A. N., Liang, J. J., El-Osta, A., Hung, A., AbuMaziad, A. S., & Karagiannis, T. C. (2023). Identification of Potential Modulators of a Pathogenic G Protein-Gated Inwardly Rectifying K Channel 4 Mutant: Investigation in the Context of Drug Discovery for Hypertension. Molecules (Basel, Switzerland), 28(24).
  More info

  Genetic abnormalities have been associated with primary aldosteronism, a major cause of secondary hypertension. This includes mutations in the gene, which encodes G protein-gated inwardly rectifying K channel 4 (GIRK4). For example, the substitution of glycine with glutamic acid gives rise to the pathogenic GIRK4 mutation, which alters channel selectivity, making it more permeable to Na and Ca. While tertiapin and tertiapin-Q are well-known peptide inhibitors of the GIRK4 channel, clinically, there is a need for the development of selective modulators of mutated channels, including GIRK4. Using methods, including homology modeling, protein-peptide docking, ligand-binding site prediction, and molecular docking, we aimed to explore potential modulators of GIRK4 and GIRK4. Firstly, protein-peptide docking was performed to characterize the binding site of tertiapin and its derivative to the GIRK4 channels. In accordance with previous studies, the peptide inhibitors preferentially bind to the GIRK4 channel selectivity filter compared to GIRK4. A ligand-binding site analysis was subsequently performed, resulting in the identification of two potential regions of interest: the central cavity and G-loop gate. Utilizing curated chemical libraries, we screened over 700 small molecules against the central cavity of the GIRK4 channels. Flavonoids, including luteolin-7-O-rutinoside and rutin, and the macrolides rapamycin and troleandomycin bound strongly to the GIRK4 channels. Similarly, xanthophylls, particularly luteoxanthin, bound to the central cavity with a strong preference towards the mutated GIRK4 channel compared to GIRK4. Overall, our findings suggest potential lead compounds for further investigation, particularly luteoxanthin, that may selectively modulate GIRK4 channels.
• AbuMaziad, A. S., Abusaleh, R., & Bhati, S. (2021). Congenital nephrotic syndrome. Journal of perinatology : official journal of the California Perinatal Association, 41(12), 2704-2712.
  More info

  Congenital nephrotic syndrome (CNS), a challenging form of nephrotic syndrome, is characterized by massive proteinuria, hypoalbuminemia, and edema. Extensive leakage of plasma proteins is the main feature of CNS. Patients can be diagnosed in utero or during the first few weeks of life, usually before three months. The etiology of CNS can be related to either genetic or nongenetic etiologies. Pathogenic variants in NPHS1, NPHS2, LAMB2, WT1, and PLCE1 genes have been implicated in this disease. The clinical course is complicated by significant edema, infections, thrombosis, hypothyroidism, failure to thrive, and others. Obtaining vascular access, frequent intravenous albumin infusions, diuretic use, infection prevention, and nutritional support are the mainstay management during their first month of life. The best therapy for these patients is kidney transplantation. CNS diagnosis and treatment continue to be a challenge for clinicians. This review increases the awareness about the pathogenesis, diagnosis, and management of CNS patients.
• AbuMaziad, A. S., Thaker, T. M., Tomasiak, T. M., Chong, C. C., Galindo, M. K., & Hoyme, H. E. (2021). The role of novel COQ8B mutations in glomerulopathy and related kidney defects. American journal of medical genetics. Part A, 185(1), 60-67.
  More info

  Glomerulopathies affect kidney glomeruli and can lead to end-stage renal disease if untreated. Clinical and experimental evidence have identified numerous (>20) genetic mutations in the mitochondrial coenzyme Q8B protein (COQ8B) primarily associated with nephrotic syndrome. Yet, little else is understood about COQ8B activity in renal pathogenesis and its role in mitochondrial dysfunction. We identified additional novel COQ8B mutations in a glomerulopathy patient and aimed to define the potential structural and functional defects of COQ8B mutations.
• Weng, P. L., Majmundar, A. J., Khan, K., Lim, T. Y., Shril, S., Jin, G., Musgrove, J., Wang, M., Ahram, D. F., Aggarwal, V. S., Bier, L. E., Heinzen, E. L., Onuchic-Whitford, A. C., Mann, N., Buerger, F., Schneider, R., Deutsch, K., Kitzler, T. M., Klämbt, V., , Kolb, A., et al. (2021). De novo TRIM8 variants impair its protein localization to nuclear bodies and cause developmental delay, epilepsy, and focal segmental glomerulosclerosis. American journal of human genetics, 108(2), 357-367.
  More info

  Focal segmental glomerulosclerosis (FSGS) is the main pathology underlying steroid-resistant nephrotic syndrome (SRNS) and a leading cause of chronic kidney disease. Monogenic forms of pediatric SRNS are predominantly caused by recessive mutations, while the contribution of de novo variants (DNVs) to this trait is poorly understood. Using exome sequencing (ES) in a proband with FSGS/SRNS, developmental delay, and epilepsy, we discovered a nonsense DNV in TRIM8, which encodes the E3 ubiquitin ligase tripartite motif containing 8. To establish whether TRIM8 variants represent a cause of FSGS, we aggregated exome/genome-sequencing data for 2,501 pediatric FSGS/SRNS-affected individuals and 48,556 control subjects, detecting eight heterozygous TRIM8 truncating variants in affected subjects but none in control subjects (p = 3.28 × 10). In all six cases with available parental DNA, we demonstrated de novo inheritance (p = 2.21 × 10). Reverse phenotyping revealed neurodevelopmental disease in all eight families. We next analyzed ES from 9,067 individuals with epilepsy, yielding three additional families with truncating TRIM8 variants. Clinical review revealed FSGS in all. All TRIM8 variants cause protein truncation clustering within the last exon between residues 390 and 487 of the 551 amino acid protein, indicating a correlation between this syndrome and loss of the TRIM8 C-terminal region. Wild-type TRIM8 overexpressed in immortalized human podocytes and neuronal cells localized to nuclear bodies, while constructs harboring patient-specific variants mislocalized diffusely to the nucleoplasm. Co-localization studies demonstrated that Gemini and Cajal bodies frequently abut a TRIM8 nuclear body. Truncating TRIM8 DNVs cause a neuro-renal syndrome via aberrant TRIM8 localization, implicating nuclear bodies in FSGS and developmental brain disease.
• Abu maziad, A. (2020). De novo truncating TRIM8 variants impair its protein localization to nuclear bodies and cause a pediatric syndrome of developmental delay, epilepsy and focal segmental glomerulosclerosis. American Journal of Human Genetics.
• Abu maziad, A. (2020). The role of novel COQ8B mutations in glomerulopathy and related kidney defects. American Journal of Medical Genetics. doi:DOI: 10.1002/ajmg.a.61909

Presentations

• Abu maziad, A. (2023, March 29, 2023). Kidney disease modeling and drug discovery using patient-derived stem cells. Research day. University of Arizona: University of Arizona.
  More info

  Oral presentation in research day. 
• Abu maziad, A. (2023, 10/20/2023). Cross-talk between actin cytoskelton and mitochndria in primary podocytopathies. Program for Kidney Health and Disease symposium. University of Arizona: Department of Physiology.
  More info

  Kidney Symposium 2023Talk Presenter: Asmaa AbuMaziad, MD, Department of Pediatrics, Division of NephrologyTitle: Cross talk between actin cytoskeleton and mitochondria in PodocytopathiesPodocytes are highly differentiated cells with a unique cytoskeletal architecture and function. Podocyte injury is characterized by actin cytoskeleton disruption and foot processes effacement. The actin cytoskeleton is crucial for the maintenance of shape and function of podocytes. Dynamic and constant active assembly and disassembly of actin fibers of the actin cytoskeleton in podocyte are essential to accommodate the filtration pressure in the glomerulus. Actin and actin-related gene mutations like alpha actinin 4, myosin IE (MYO1E), alpha 3 integrin (ITGA3), CD2-associated protein (CD2AP), and other mutations can cause actin cytoskeleton dysfunction leading to nephrotic syndrome, loss of podocytes death, and focal segmental glomerulosclerosis (FSGS) pattern. Mitochondria play a fundamental role in regulation of cellular function such as respiration, calcium hemostasis, reactive oxygen species (ROS) generation, ATP synthesis, apoptosis, and other metabolic functions. Cytoskeletal and mitochondrial abnormalities are predominant features in many disease states including neurodegeneration, cardiomyopathies, and others. Cytoskeletal dysfunction can lead to impairments in mitochondrial respiration and activate apoptosis, thereby accelerating disease progression. Here, the multiple complexes of mitochondria with cytoskeleton proteins may represent a potential therapeutic target in the management of podocytopathies. We study actin cytoskeleton dysfunction and mitochondria functions in immortalized podocyte cell line and kidney organoids system using patients’ iPSC.
• Abu maziad, A. (2023, April 15, 2023). Innovative Approaches to Define Disease Mechanisms and Therapies. Translational Medicine Workshop. University of Arizona, Tucson, Lodge on the Desert Palm Room: University of Arizona.
• Abu maziad, A. (2023, September 7, 2023).

  Cross-talk between actin cytoskeleton and mitochondria in primary podocytopathies

  . Re-Build Kidney consortium (RBK)/NIHNIH.
  More info

  I presented a talk about my research work to national consortiumRe-Build Kidney Consortium (RBK)
• AbuMaziad, A. S. (2019, Feb. 13, 2019). Mass Cytometry to Identify the Immune Dysregulation of Systemic Lupus Erythematosus/Lupus Nephritis and the Role of Microbiota. Research Day 2019. University of Arizona, Health Sciences Innovation Building (HSIB).: University of Arizona.
  More info

  Type of presentation: Oral Date: 2/13/2019Abstract: (please see attached PDF)Systemic Lupus Erythematosus (SLE) is a severe, complex heterogeneous multi-system autoimmune disease characterized by loss of tolerance against self-antigens, polyclonal autoantibody production, immune complex formation, and activation of complement leading to inflammation and multiorgan injury. The incomplete understanding of the pathogenesis of SLE results in non-targeted therapies. In this study, first, we will enroll patients with SLE both pediatric and adult cohort at initial diagnosis, disease flare, and during remission (each group n= 20) as well as control cohort (n=20). Second, we will characterize gut microbiota in patients with SLE using whole metagenomic analysis. Third, we will perform single-cell phenotypic and functional characterization of SLE patients’ blood via mass cytometry (CyTOF). CyTOF analysis will enable us to evaluate immune dysregulation in SLE by discovering a multi-parametric immune signature that may drive disease pathogenesis and will delineate the role of gut microbiota in disease development.

Poster Presentations

• Abu maziad, A. (2023, 11/2/2023). Molecular Mechanisms of Novel NPHS2 Pathogenic Variants and Proposed Therapeutic Interventions. ASN Kidney Week 2023 in Philadelphia, PA. ASN Kidney Week 2023 in Philadelphia, PA: American Society of Nephrology (ASN).
  More info

  Presented a poster: Molecular Mechanisms of Novel NPHS2 Pathogenic Variants and Proposed Therapeutic Interventions
• Abu maziad, A. (2023, 5/2023). Mitochondrial Biogenesis and Therapeutic Interventions in Podocytopathies Using Novel Approaches. 14th International Podocyte Conference, PA. 14th International Podocyte Conference, PA.
  More info

  May 24-26, 2023
• Abu maziad, A. (2019, November). The Role of Novel ADCK4 Mutations in Glomerulopathy and Related Kidney Defects. American Society of Nephrology (ASN) 2019. Washington DC.
• Abu maziad, A. S. (2019, November). Kidney Biopsy Proteome Reveals Molecular Pathway Heterogeneity BetweenDifferent Classes of Lupus Nephritis. American Society Of Nephrology (ASN) 2019 Washington DC. Washington DC.

Reviews

• Abu maziad, A. (2020. Congenital nephrotic syndrome.