Fata Moradali, PhD

Fata Moradali, PhD

Assistant Professor

Email: fata.moradali@louisville.edu

ORCID ID: 0000-0002-0230-5006

Research Interests:

The oral cavity contains one of the most diverse, complex, and unique communities of aerobic and anaerobic microbes in the human body with strong implications in health and a range of diseases e.g. dental caries, gum infections, inflammation, cancers, cardiovascular diseases, Alzheimer’s disease, and autoimmune diseases. Current working models suggest that perturbation and imbalance in microbiome homeostasis, so-called dysbiosis, and the transition of a community of commensal microbes to a pathogenic state are strongly associated with disease state. My laboratory is focused on leveraging interdisciplinary, innovative system-based approaches, and integrating the tools of molecular/cellular biology, biochemistry, and systems biology to better understand the complex system of human host-oral microbiome, the causative factors and mechanistic basis of commensal-to-pathogen transition, and its impact on host cell functions and the immune system, leading to persistent infections and chronic inflammations. Further, we are working to advance identification of diagnostic biomarkers/therapeutic targets as well as development of novel therapeutic approaches, cell factories, and bioactive components to overcome chronic inflammation/infections and associated diseases.

Major Projects

Cell reprogramming, genomic, metabolic, and phenotypic adaptations in human host-oral microbiome system during gum infections- Integrating -omics and molecular/cellular analyses on a model system simulating ecophysiological condition of the subgingival niche for understanding adaptive molecular mechanisms underlying the commensal-to-pathogen transition, with an emphasis on the key anaerobic pathogen Porphyromonas gingivalis, with the ability to evade the immune system, alter the nature of the infected cells, and reprogram host cellular processes for promoting chronic infections and inflammation with adverse systemic effects on human health.

Fata Moradali Figure 1
Our approach, which is based on simulating the sandwich environment of the subgingival crevice, has demonstrated that the key anaerobic pathogen P. gingivalis is fully capable of complex surface migration; it requires modification of the surrounding environment via proteolysis, hydration, cell dispersion, cell-on-cell rolling, and sub-diffusive cell-driven motility. Schematic illustration represents an alteration of the metabolism, gene expression profile, and virulence factors during the biofilm-migration switch (Ref: Moradali MF, et al. 2019. The ISME Journal, 13: 1560–1574).

Key signaling networks and molecular dialogues in human host–oral microbiome system, promoting persistent infections and inflammation- Signaling molecules and molecular dialogues control fundamental regulatory and adaptive mechanisms in all living organisms to broadcast perceived stimuli to key cellular processes for promoting adaptation to specific environmental stimuli and ecophysiological conditions. My current project in this field focuses on studying second messenger signaling pathways, with an emphasis on cyclic (di-)nucleotides signaling in the predominant oral pathogens strongly implicated in the development of chronic inflammations of the periodontal tissues, in addition to understanding metabolic dialogues in human host–oral microbiome systems that control the expression of key virulence/pathogenicity-related genes as well as rewire host cellular responses.

Fata Moradali Figure 2
Schematic illustration represents the broadcast of stimuli to cellular processes via cyclic (di-) nucleotide second messengers in the Gram-negative bacteria for promoting persistence, pathogenesis, and adaptation to the host and environmental factors. In fact, there is a delicate equilibrium between biosynthesis and degradation of second messengers; upon alterations in their concentrations, specific receptors such as proteins and riboswitches are engaged to act as direct effectors for controlling the output responses at translational and/or post-translational levels. In principle, such signaling systems not only determine pathogenesis state but also impact host-pathogen interactions and the state of immune responses.

Biopolymers and cell factories: from pathogenesis to biomedical applications- Biopolymers, such as polysaccharides, polyamides, glycoproteins, polyesters, extracellular DNA, polyphosphates, are synthesized by processive enzymes of living organisms to yield high molecular weight molecules with unique physicochemical properties and biological functions. Polymeric substances can function as protective layers surrounding cells, and also serve as major matrix components to form complex dynamic niches for molecular and cellular interactions with strong implications in the development of persistent infections and tumorigenesis. I am interested in understanding synthesis, natural modification, and molecular interaction of biopolymers, in particular, produced by bacteria and tumor cells not only to identify new therapeutic targets but also to design novel cell factories (or bugs as drugs) for producing innovative tailor-made bio-based materials and drugs with high-value biomedical applications. My current research in this field focuses on producing innovative tailor-made polysaccharides with the potentials for combating persistent biofilm-based infections and anti-inflammatory properties, in addition to designing three dimensional (3-D) models based on tissue and matrix engineering to study the complex web of human host–oral microbiome interactions.

Fata Moradali Figure 3
Molecular biology and biochemical or biophysical approaches have provided insight into biosynthesis pathways of biopolymers. Production of novel biopolymers can be achieved by synthetic biology for the development of cell factories or ”bugs as drugs” for production of tailor-made bio-based materials and wide-ranging valuable compounds with unique properties for biomedical purposes. In vitro enzymatic synthesis or modification of biopolymers as well as chemical modifications can achieve novel biopolymers with altered material properties and functions. Selective inhibition of biopolymers that function as virulence factors or matrix components offers targets for antimicrobial and anti-tumor drug discovery. (Ref: Moradali MF & Rehm BHA. 2020. Nature Reviews Microbiology, 18, 195–210)

Selected publications

  1. Biopolymers for biomedical and biotechnological applications. John Wiley & Sons. (2021)
  2. Microbial cell factories for biomanufacturing of polysaccharides. In: Biopolymers for biomedical and biotechnological applications. John Wiley & Sons. (2021)
  3. PPAD activity promotes outer membrane vesicle biogenesis and surface translocation by Porphyromonas gingivalis. Journal of Bacteriology (2020) (DOI: 10.1128/JB.00343-20)
  4. Bacterial biopolymers: from pathogenesis to advanced materials.  Nature Reviews Microbiology, 18, 195–210 (2020) (DOI: 10.1038/s41579-019-0313-3)
  5. The regulation of alginate biosynthesis via cyclic di-GMP signaling. In: Microbial cyclic di-nucleotide signaling. Springer, Cham. (2020) (DOI: 10.1007/978-3-030-33308-9_14)
  6. Amino acids as wetting agents: surface translocation by Porphyromonas gingivalis. The ISME Journal, 13: 1560–1574(2019) (DOI: 10.1038/s41396-019-0360-9)
  7. The role of alginate in bacterial biofilm formation. In: Extracellular sugar-based biopolymers matrices. Biologically-inspired systems, vol 12. Springer, Cham. (2019) (DOI: 10.1007/978-3-030-12919-4_13)
  8. Alginates and their biomedical applications. Springer. (2018)
  9. Activation mechanism and cellular localization of membrane-anchored alginate polymerase in Pseudomonas aeruginosa. Applied and Environmental Microbiology, 83 (9) e03499-16. (2017) (DOI: 10.1128/AEM.03499-16)
  10. Alginate polymerization and modification are linked in Pseudomonas aeruginosa. mBio, 6 (3) e00453-15 (2015) (DOI: 10.1128/mBio.00453-15)