The University of Newcastle, Australia

At the top of our lungs

Dr Fatemeh Moheimani is investigating how the structure and function of airway epithelium contribute to respiratory disease, with the end goal of developing novel interventions for asthma.

Considerable experience in cardio-vascular research employing different techniques across several laboratories has furnished Dr Fatemeh Moheimani with the skills needed to excel in her most recent area of focus in respiratory disease research, in particular, the airway epithelial cells in asthma.

Fatemeh is looking at what is happening at tissue and molecular level inside the lungs of asthma sufferers.

“Since the air we breathe is common between people who suffer from asthma and those who don’t, there should be underlying mechanisms at tissue and molecular level, responsible for asthma development,” Fatemeh explains.

“I am interested in understanding these mechanisms.”

“If we understand the mechanism involved, we can then offer an approach to manage the disease.”

Coming from RMIT in 2013 to establish Professor Darryl Knight’s Airway Cell Biology Laboratory and lead asthma research program in this laboratory at the Hunter Medical Research Institute (HMRI), Fatemeh has quickly proven she is more than capable of rising to the challenge of mastering a new area of focus whilst running a world-class research facility.

TRANSFORMING CELLS

The epithelium is the thin tissue lining the outer layer of the airway surface and is the first protective barrier between inhaled particles, for example allergens and viruses, and the internal environment of the lung.

“The airway epithelium has a pseudostratified structure,” Fatemeh says, “meaning although airway epithelium comprises a single layer of cells which are resting on a basement membrane, the nuclei of these cells are positioned in a manner suggestive of a multilayer structure of cell populations.”

“Some of these cells are like stem cells, we call them basal cells - they are able to divide and produce more cells. They can stay as basal cells or they can differentiate to different types of cells.”

Some cells produce mucus which lubricates the surface for protection against scratches from foreign particles. Other cells develop cilia, tiny hairs that aid in the removal of the foreign particles through a constant pulsing.

The balance between these cell populations is essential for normal function of the epithelium in the lung. Unfortunately, this balance isn’t always achieved in asthmatics.

ENTER ASTHMA

In asthmatics, cells predominantly stay in the stem cell or basal cell mode. These abnormalities in asthmatic epithelium prevent normal regeneration after epithelial wounding, resulting in a cycle of inflammatory and detrimental effects.

“The focus of the lab is trying to understand further what is happening during the whole process of epithelial cell proliferation and differentiation, so we can identify why asthmatic epithelium behave in a divergent manner,” Fatemeh clarifies.

“We also assess the effect of viral infections on airway epithelial cells.”

“We know that there are different cellular mechanisms that determine the fate of cells, and whether they remain undifferentiated or differentiate to more mature cells.”

These mechanisms are being investigated with a focus on identifying the precise roles of epigenetic factors which is defined as how environmental factors can influence gene expression.

“I’m particularly looking at microRNAs, they are biological regulatory factors and they are silencing RNA and post-transcriptionally regulating gene expression,” Fatemeh says.

Proteins are also an important part of the equation in the structure of cells and connect the epithelial cells to each other and their underlying structure. Each microRNA targets different proteins.

“If we can find out, for example, that a particular cell is lacking or overexpressing a specific (or group) of microRNA with essential targets important in the process of epithelial cells homeostatic, that would be a breakthrough.”

“Then we could work on a proper intervention for asthma.”

COMING FULL CIRCLE

Fatemeh’s journey to her current position has been long and impressive.

After completing a doctorate degree in pharmacy in Iran (Pharm-D), she migrated to Australia to follow her passion for research.

Moving to the University of Adelaide in 2003, after working briefly for the University of Newcastle, she completed a Masters of Medical Science by research, investigating the effect of a novel polyunsaturated fatty acid on the development of atherosclerosis in apoE deficient mice.

A short stint at the Flinders Medical Centre followed before Fatemeh was offered an APA scholarship from the University of Sydney to undertake a PhD.

“My PhD was about cardiovascular disease in people with diabetes. I looked at the molecular mechanism linking diabetes with atherosclerosis,” she affirms.

Joining RMIT’s Thrombosis and Vascular Diseases Laboratory as a postdoctoral researcher in 2010, Fatemeh focused on the role of different regulatory mechanisms of platelets during thrombosis formation. Here, she also gained invaluable experience in co-supervising and mentoring postgraduate students.

Fatemeh returned to Newcastle in 2013 as a postdoctoral fellow to work with Professor Darryl Knight, a preeminent expert on airway epithelium and respiratory diseases.

LAB IMITATES LIFE

Clearly fascinated by the mechanisms she is studying, Fatemeh animatedly describes a protocol developed by Professor Knight and other scientists to create a mimic in vitro epithelium for study.

“We use an air liquid interface technique (ALI) here in the lab where we can grow the primary epithelial cells in a pseudostratified structure,” she divulges.

“A special media then helps epithelial cells to develop different population of the cells and differentiate - we can see the cilia beating, and the mucus production.”

“We can use this to look at the different targets, because we already have those differentiated cells in the tissue culture in the lab.”

“We can also assess how viral infections affect airway epithelium. It is amazing!”

Much lauded and with a history of varied research behind her, one is left to wonder what body part Fatemeh will become expert in next.

“At the moment I am focusing on understanding the underlying mechanisms responsible for respiratory diseases, particularly at airway epithelium level,” she states.

“Airway epithelium is the first barrier, first defense of your body, between inside and outside. In any lung disease it plays a very important role.”

“But,” she says, smiling, “the human body is complex, just one layer, one part, one tissue is not the entire thing. There is so much to discover and learn.”

SURPRISE PATHS

Ever humble, Fatemeh laughs away any suggestion that her dedication and achievements are awe-inspiring.

“I am telling you, the whole way through I have always worked with passionate and fabulous people,” Fatemeh attests.

One of her roles in the lab is supervising/mentoring of students and junior staff. Experience has afforded Fatemeh a philosophical approach to her research that she shares with her mentees.

“It is good to have a goal and then find your way towards it,” she observes.

“But sometimes it doesn't always go as you expect, that is the beauty of research. If one thing doesn't work, you try to find a reason for that, and you may go in a completely different direction and find something important there.”

“It is not easy, and it is not a one person job. But the people, the equipment and the technology at HMRI are not like anywhere else, it is remarkable,” she asserts solemnly.

“There is not a day that I walk in here and I don't want to be here. It is such an amazing feeling that my research may contribute in easing the pain of asthma sufferers one day.”

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