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Research Interests:    

Dr. Hussain’s research group focuses on elucidating the molecular mechanisms of environmental disease susceptibility by delineating regulatory signaling networks involved in the susceptibility to environmental stressors including nanomaterials, particulate matter and ozone. We are interested in elaborating the pulmonary health effects of various environmental and occupational toxicants using translation relevant primary human cell models as well as rodent inhalation exposures. We have previously studied impacts of titanium dioxide, gold, cerium dioxide, carbon nanotubes and mycotoxins using disease animal models (occupational asthma and skin sensitization) and 3D primary human cell models from healthy and disease individuals.  

Figure:Mechanistic Exploration of Cell Death Pathways after Nanomaterial Exposures

Theme 1:  Mechanistic and Translational NanoBiology  

A. Mechanisms of Programmed Cell Death Pathway Activation by Environmental Exposures  

Programmed cell death pathways play a critical role in dictating the pathophysiology of environmental diseases. Over the past decade we have elaborated environmental exposures mediated programmed cell death pathways activation using various translational in vitro and in vivo models. For future studies, we are interested in delineating the cross-talk between various cell survival and injury pathways and mitochondrial dynamics after environmental exposures.  

Figure: Epithelial NLRP3 inflammasome activation leads to a pro-fibrotic gene expression after multi-walled carbon nanotube exposure of primary human cells

   

B. 3-Dimensional Translational Models of Human Lung Epithelium 

We work on 3-dimensional models of primary human and murine airways cultured at air-liquid interface to study the molecular mechanisms initiated by environmental exposures. We are interested in studying the modulation of airway differentiation and use it as a translational model to elaborate mechanisms of environmental injury in healthy and disease conditions.  

Figure: Co-cultures of differentiated primary human bronchial epithelial cells with primary human lung fibroblasts at air-liquid interface. Figures demonstrating morphology, mucociliary differentiation and Immunohistochemical labelling for Ki-67 after multi-walled carbon nanotube exposure.

C. Application of Safety by Design Approach to Nanomaterial Risk Assessment

We are studying biocompatibility of novel nanomaterials for biomedical applications. We have previously employed functionalization of multi-walled carbon nanotubes (MWCNT) with high molecular weight hyaluronan (HA), a naturally occurring extracellular matrix sugar with excellent safety profile and significant anti-inflammatory properties, as a novel way to reduce pulmonary toxicity of MWCNT (Hussain et.al. ACS Nano 2016). We are now elaborating the role of different physico-chemical characteristics and other forms of surface functionalization’s and in delineating the role of mitochondrial injury and different intra-cellular signaling pathways.   

Theme 2: Modulation of Disease Susceptibility by Environmental Exposures

We are studying the impacts of particulate exposures on the pathophysiology of pulmonary diseases and metabolic syndrome. We have previously demonstrated significant impacts of nanomaterial exposures on asthmatic responses as well as skin sensitization in rodents. We are currently exploring the mechanistic basis of these mechanisms using translational primary human cell models from health and disease individuals. We have shown the significant contribution of innate immune mechanisms particularly originating from Toll-Like Receptors in changing susceptibility to environmental disease like Asthma, fibrosis, COPD and metabolic syndrome.   

Theme 3: Gestational and early life origins of adult onset disease

We are currently elaborating developmental origins of pulmonary diseases by studying the impacts of gestational and early life exposures to inhaled environmental stressors. We are employing individual as well as co-exposure scenarios and are studying the intricate interplay of cell survival and injury pathways as well as genetic and epigenetic mechanisms that govern susceptibility.        

Techniques:

  • Inhalation Exposures (particles, ozone etc)
  • Disease Animal Models (Asthma, Fibrosis, COPD, Contact Sensitivity)
  • Airway Physiology Measurements (Flexivent System)
  • Primary Cell Cultures (Human and Rodent)
  • 3-D Airway Epithelial Cell Models (Human and Rodent)
  • Isolation, Culture and Study of Various Cell Types from Lungs, Blood and Bone Marrow
  • Transgenic, floxed and conditionally KO mouse models
  • Translational Studies