A stroke of magic

Professor Bronwen Connor is a successful neuropharmacologist and in 2018 was made a Member of the New Zealand Order of Merit for contribution to the treatment of neurological disease. She shares her journey into research.

Sometimes I look back and wonder how I got to where I am today. I look at my journey as one that was unplanned and serendipitous in many ways. I grew up in a household where science was part of my life. My father has a degree in engineering and physics and many of my childhood memories are based around him helping me with school science projects and making crystal radio sets. However, physics was not my forte, and I leaned towards Biology and English at high school. My Dad’s advice for me was “keep your options open”. So, I left high school with Bursary level English, Biology, Maths, Chemistry and Physics.

The other main aspect of my life was rowing. From the ages of 16 - 18 I was a member of the NZ U19 Rowing Squad. Rowing was my passion and my life. I started my first year at University of Auckland planning to do a Bachelor of Science (BSc) in Exercise Science with an interest in enhancing sporting performance. One of the papers I took in my first year at university was General Psychology. I remember opening the course textbook and reading about the brain.

And that was it, I was hooked! I changed the focus of my degree to neuroscience taking courses in psychology and neurophysiology. Then, in my final year, I found the last missing piece to the puzzle, pharmacology.

Finally, I knew the direction I wanted my life to take. Working in the area of drug development for the treatment of neurological disorders.

At the end of my BSc I had to decide whether to continue at university and do a graduate degree or take a break and trial for the New Zealand women’s Olympic rowing squad. However, this decision was made for me as I seriously injured my back during training, ending my rowing career. I therefore turned my attention to my new passion, the brain, and enrolled in a Master of Science (MSc) with Professor Mike Dragunow in the Department of Pharmacology at the University of Auckland. My research investigated whether the expression of growth factors, endogenous compounds that provide support to neurons, were altered in Alzheimer’s disease using post-mortem human brain tissue from the Neurological Foundation Human Brain Bank. Within a year I had upgraded to a PhD with co-supervision by Distinguished Professor Richard Faull. I completed my PhD in 1997 and took up a postdoctoral position at Northwestern University in Chicago under the supervision of Professor Martha Bohn investigating the potential use of GDNF (glial cell-derived neurotrophic factor) gene therapy for the treatment of Parkinson’s disease. My postdoctoral fellowship was supported by funding from the Neurological Foundation. I was the first recipient of the Philip Wrightson Fellowship.

The three years I spent working at Northwestern University were incredible. The field of gene therapy was very new and the concept of using this technology to deliver compounds too large to cross the blood brain barrier, such as GDNF, was very exciting. The research we performed at Northwestern University was pioneering and recently, GDNF gene therapy for the treatment of Parkinson’s disease went into clinical trial lead by a former PhD student of mine, Dr Adrian Kells at Brain Neurotherapy Bio Inc.

After my time at Northwestern University, I started my academic career at the University of Auckland in June 2000. Over the past 20 years I have been involved in a lot of exciting projects and worked with many wonderful people. On my return to New Zealand I continued my work in gene therapy, focusing on the use of gene therapy for the treatment of Huntington’s disease. We were the first to demonstrate that delivery of the growth factor BDNF (brain-derived neurotrophic factor) to the brain using gene therapy can prevent the selective loss of neurons in the striatum in animal models of Huntington’s disease.

I also collaborated with Distinguished Professor Richard Faull, Professor Mike Dragunow and Professor Maurice Curtis (then a doctoral student) on the unique discovery that the Huntington’s disease human brain could generate new replacement brain cells in response to cell loss, a process known as compensatory neurogenesis. This work was funded by the Neurological Foundation. I extended this work into a rodent model of Huntington’s disease to identify specific cues and signals expressed by the damaged brain which promote compensatory neurogenesis. Identification of these factors could lead to the development of drugs to enhance the brain’s self- repair process. We demonstrated that factors known as chemokines, which are expressed in the initial stages of inflammation, are vital in directing the migration of resident adult brain stem cells to areas of damage. However, while we identified targets to promote the recruitment and maturation of resident adult brain cells in areas of damage, we have been unable to successfully suppress the prolonged inflammatory response that occurs and eventually destroys the newly formed brain cells.

In 2007, the field of biomedical science was turned upon its head with the unique discovery of cell reprogramming lead by Professor Yamanaka of Kyoto University. By over-expressing key developmental genes, he showed that human skin cells could be turned into embryonic stem cells. Pure magic! These cells are called induced pluripotent stem cells (iPSCs) and can generate all cell and tissue types in the body. Using this technology, we can generate human brain stem cells that can be used either to model neurodevelopmental or neurological diseases, or to provide a source of ethically viable cells for cell replacement therapy. In 2010, with support of the Neurological Foundation, I refocused my research to develop our own novel strategy to reprogram adult human skin cells directly to brain stem cells, without needing to first create embryonic stem cells. Our technology is faster, safer and more efficient than the iPSC technology. The beauty of this technology is we can generate live human brain cells to study specific neurodevelopmental or neurological disorders where previously we were restricted to the use of either animal models or post-mortem human tissue. This allows us to investigate disease progression as the stem cells develop to mature neurons, providing a unique opportunity to identify novel therapeutic targets for drug development. We are currently undertaking projects using our direct cell reprogramming technology to investigate the disease process of the neurodevelopmental disorder Fragile X Syndrome; and have completed a project that identified potential drug targets for the treatment of Huntington’s disease.

Over the last 20 years I have had the opportunity to work with many wonderful people, the staff, post- doctoral fellows and graduate students that have made up my research group. I have supervised 13 doctoral students, with 8 of these being awarded a Neurological Foundation postgraduate scholarship to support their PhD, 9 Masters students and 18 BSc Honours students.

Throughout my career, my greatest accomplishment and joy has been my graduate students. I watch them discover the magic and excitement of neuroscience and grow as scientists and individuals during the progress of their research to emerge as independent and accomplished researchers. Their energy, passion and enthusiasm never cease to amaze me and pushes me to be the best that I can be. This is the true gift of my job. 

I have been awarded a total of 18 small and full project grants from the Neurological Foundation. Thank you, to all the supporters throughout my career that have made my research possible. I am truly grateful for the opportunities that the supporters of the Foundation have provided me.

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