Dr Shirley Huan Fang Lee

I completed my PhD from University of Cambridge in 2014, specializing in Medical Genetics (autophagy and neurodegenereration; role of microtubules in autophagy initiation) at the Cambridge Institute for Medical Research (CIMR) under the supervision of Professor David Rubinsztein (and Dr. Fiona Menzies).

Autophagy is an intracellular bulk degradation mechanism which involves formation of a C-shaped membrane structure (phagophore), which elongates and then seals off to engulf proteins/substrates targeted for degradation. The sealed double-membrane structure containing target proteins is trafficked towards the lysosomes which contains hydrolytic enzymes to break down the proteins destined for degradation into amino acids. This provides a way to recycle energy sources within a cell, particularly in nutrient starvation conditions. Besides nutrient starvation, autophagy can also be stimulated via growth factor deprivation and through mTOR (mammalian target of rapamycin) inhibition or rapamycin (a drug which inhibits mTOR). mTOR is an important serine/threonine kinase, which is commonly reported to be misregulated in various cancers.

I was interested to dissect the mechanisms which initiate autophagy leading to early membrane formation which eventually gives rise to autophagosomes. My PhD involves investigating the role of cytoskeleton (microtubules and actin) in autophagy, particularly in autophagosome biogenesis. I studied the role of cytoskeleton, especially microtubules in membrane trafficking during the initiation of autophagy. I was also interested to understand if microtubule post-translational modification occurs during starvation-induced autophagy.

The role of microtubule-associated motor (kinesin-1) was also investigated. The working model of my thesis is that cytoskeleton is required for intact autophagy in the early stage (autophagosome biosynthesis), and that microtubule post-translational modification (decrease in tubulin/microtubule acetylation) occurs during starvation-induced autophagy. This may influence their interaction with microtubule motors, such as kinesins and/or dyneins to alter directionality/trafficking velocities of membrane proteins to influence autophagy.

EDUCATION

I completed my PhD in 2014 in Cambridge Institute for Medical Research (CIMR), University of Cambridge. Prior to that I was in Imperial College London (2008-2009) and obtained a Masters (Msc) in Human Molecular Genetics. My undergraduate years (2005-2008) were spent in Trinity College, University of Cambridge, where I read Natural Science (Genetics).

RESEARCH INTERESTS

Neurodegeneration, neurology
Ageing
Cancer

RECENT PUBLICATIONS

1) Lim, Ya, Rajan Rajabalaya, Shirley Lee, Kushan Tennakoon, Quang-Vuong Le, Adi Idris, Ihsan Zulkipli, Natasha Keasberry, and Sheba David. 2016. “Parasitic Mistletoes of the Genera Scurrula and Viscum: From Bench to Bedside.” Molecules 21 (8). Multidisciplinary Digital Publishing Institute: 1048. doi:10.3390/molecules21081048.
2) Moreau, K., Ghislat, G., Hochfeld, W., Renna, M., Zavodszky, E., Runwal, G., … Rubinsztein, D. C. (2015). Transcriptional regulation of Annexin A2 promotes starvation-induced autophagy. Nature Communications, 6, 8045. http://doi.org/10.1038/ncomms9045
3) Hochfeld, W. E., Lee, S., & Rubinsztein, D. C. (2013). Therapeutic induction of autophagy to modulate neurodegenerative disease progression. Acta Pharmacologica Sinica, 34, 600–4. http://doi.org/10.1038/aps.2012.189
4) Ellison, S. M., Trabalza, A., Tisato, V., Pazarentzos, E., Lee, S., Papadaki, V., … Mazarakis, N. D. (2013). Dose-dependent neuroprotection of VEGF165 in Huntington’s disease striatum. Molecular Therapy : The Journal of the American Society of Gene Therapy, 21, 1862–75. http://doi.org/10.1038/mt.2013.132

TOP PUBLICATIONS

1) Lim, Ya, Rajan Rajabalaya, Shirley Lee, Kushan Tennakoon, Quang-Vuong Le, Adi Idris, Ihsan Zulkipli, Natasha Keasberry, and Sheba David. 2016. “Parasitic Mistletoes of the Genera Scurrula and Viscum: From Bench to Bedside.” Molecules 21 (8). Multidisciplinary Digital Publishing Institute: 1048. doi:10.3390/molecules21081048.
2) Moreau, K., Ghislat, G., Hochfeld, W., Renna, M., Zavodszky, E., Runwal, G., … Rubinsztein, D. C. (2015). Transcriptional regulation of Annexin A2 promotes starvation-induced autophagy. Nature Communications, 6, 8045. http://doi.org/10.1038/ncomms9045
3) Hochfeld, W. E., Lee, S., & Rubinsztein, D. C. (2013). Therapeutic induction of autophagy to modulate neurodegenerative disease progression. Acta Pharmacologica Sinica, 34, 600–4. http://doi.org/10.1038/aps.2012.189
4) Ellison, S. M., Trabalza, A., Tisato, V., Pazarentzos, E., Lee, S., Papadaki, V., … Mazarakis, N. D. (2013). Dose-dependent neuroprotection of VEGF165 in Huntington’s disease striatum. Molecular Therapy : The Journal of the American Society of Gene Therapy, 21, 1862–75. http://doi.org/10.1038/mt.2013.132