Researchers

Rink-Jan Lohman

Title: Dr

First name: Rink-Jan

Surname: Lohman

Web Site:

E-mail: r.lohman@imb.uq.edu.au

 Background:
 
After finishing an undergraduate degree in science at The University of Melbourne, with majors in anatomy and physiology, I found my interest leaning towards neuroscience. I received first class honours under Prof. John Furness of the Department of Anatomy and Cell biology also at Melbourne University the following year, investigating the role of N-type voltage-gated calcium channels in myenteric neurons. I then pursued an early career as a research assistant under Prof. John Furness investigating a proof-of-concept research into urinary stress incontinence in rabbits using electronic implantable devices. Having successfully proven the principle, I moved into the field of epileptology under Prof. Terry O’Brien at the Department of Medicine at the Royal Melbourne Hospital, initially working as a research assistant. This role involved investigating the progression of epilepsy (epileptogenesis) in various animal models of the disease, and the histopathologies associated with the condition. Whilst in this role, I began to develop a keen interest in the field of pharmacology, particularly with regards to centrally (brain)-expressed protease activated receptor 2 (PAR2), the trypsin receptor known to be involved in inflammation. From this research my interest into the inner workings of the brain began to grow, particularly the pathogenesis of conditions of the brain that involve an inflammatory event or considered to be auto-inflammatory (stroke, Alzheimer’s disease, epilepsy, motoneuron disease, multiple sclerosis). This interest was focused particularly on certain protein-cleaving enzymes, called proteases, which are involved in tissue remodeling and destruction during inflammation. Thus I began a PhD under Prof. Tom Cocks and Prof. Terry O’Brien of The University of Melbourne investigating the role for PAR2 in epileptogenesis, thus not only establishing a potential role for these receptors in epileptogenesis, but also its endogeneous activating enzyme, trypsin (and like proteases such as mast cell tryptase). The results of my PhD suggest that trypsin and similar proteases (tPA) up-regulate during pro-epiletogenic inflammatory stimuli, and that this increase in protease activity may contribute to epilepsy. Agonsim of PAR2 on the other hand appears to reduce the trypsin levels expressed by the brain, which translates to a reduced propensity of neuronal degradation and the development of seizure and epilepsy. This suggests a autocrine negative feed-back loop provided by trypsin and PAR2. From this data we also discovered that trypsin and PAR2 are most likely also involved in the process of fear-aversive learning and memory. The question now is how does antagonism of the receptor affect normal and pathological brain function?

Today, I reside in Brisbane, and work at The Institute for Molecular Bioscience at The University of Queensland. I am pursuing a post-doc investigating the role of a novel PAR2 antagonist in the progression of mainly peripheral auto-inflammatory disease such as arthritis. My role in the laboratory involves the primary in vivo pharmacological testing of novel anti-inflammatory compounds in various animal models of disease to determine whether they may be suitable as therapeutics for similar conditions in the human. Ultimately we hope to develop a compound that will be effective as a potent anti-inflammatory in the human that can improve the quality of life.

The Fairlie lab at the IMB is a dynamic and high class research environment. It has a large foreign influence, which makes the IMB an attractive and exciting place for medical research. There is a world of expertise, and a great sense of camaraderie.

Research interests:
* Protease-activated receptor 2 (PAR2), trypsin and other serine proteases, particularly those centrally or neuronally expressed.
* Auto-inflammatory diseases, particularly of the brain, such as epilepsy, stroke, Alzheimer’s disease and multiple sclerosis, but also peripheral conditions such as rheumatoid arthritis, asthma and colitis (most involve PAR2!)
* Novel anti-inflammatory compounds, particularly those that target novel inflammatory pathways.
* Anatomy, physiology, surgery and anaesthesia
* Pharmacology and pharmacokinetics
* Histopathology, immunohistochemisrty
* In vivo research and animal welfare. Is the animal research done ethically and properly?

Publications:
Lohman, R.J., Jones, N.C., O'Brien, T.J., and Cocks, T.M. (2009). A regulatory role for protease-activated receptor-2 in motivational learning in rats. Neurobiol Learn Mem.

Lohman, R.J., O'Brien, T.J., and Cocks, T.M. (2008). Protease-activated receptor-2 regulates trypsin expression in the brain and protects against seizures and epileptogenesis. Neurobiol Dis 30, 84-93.

Lohman, R.J., Liu, L., Morris, M., and O'Brien, T.J. (2005). Validation of a method for localised microinjection of drugs into thalamic subregions in rats for epilepsy pharmacological studies. J Neurosci Methods 146, 191-197.

Vogalis, F., Harvey, J.R., Lohman, R.J., and Furness, J.B. (2002). Action potential afterdepolarization mediated by a Ca2+-activated cation conductance in myenteric AH neurons. Neuroscience 115, 375-393.



 

Former Group Members