Martin Lab

Abstract image: bright green lines webbing out like tree branches over a black background
Ian Martin

Ian Martin
Ph.D., Virginia Commonwealth University, 2008
Postdoctoral Fellow, Johns Hopkins University, 2009–2015
Faculty profile

Ian received his B.S. degree from King's College, London and Ph.D. from Virginia Commonwealth University where he studied the impact of oxidative stress in determining life span and age-related functional declines in Drosophila. In 2009, he joined Ted and Valina Dawson's laboratory at Johns Hopkins University where he worked on molecular pathways underlying Parkinson's disease development linked to mutations in LRRK2 (leucine-rich repeat kinase 2). His work led to the discovery that mutant LRRK2 causes neurodegeneration through elevated bulk protein synthesis which is mediated by increased phosphorylation of the LRRK2 substrate ribosomal protein s15. In September 2015, Ian joined the Jungers Center as Assistant Professor of Neurology with membership in the Parkinson Center of Oregon. Further Martin Lab information

Molecular Pathogenesis of Parkinson's Disease

Parkinson's disease (PD) is a common neurodegenerative movement disorder which can be caused by a number of single-gene mutations as well as environmental risk factors. The goal of our laboratory is to define key pathogenic mechanisms underlying neurodegeneration in PD by investigating how disease-causing mutations impact neuronal function. We use a combination of Drosophila melanogaster genetic models of disease with mammalian cell culture for this purpose and our approach incorporates numerous biochemical, molecular and imaging techniques. One area of interest is on the role of LRRK2 kinase activity in disease development. Biochemical studies indicate that mutations in the kinase domain of LRRK2 increase its kinase activity and multiple disease models demonstrate that LRRK2 toxicity is kinase-dependent. Mutant LRRK2 has been proposed to impact bulk protein synthesis through enhanced ribosomal protein phosphorylation and other possible mechanisms (Figure). Importantly, neurodegenerative phenotypes in flies expressing disease-causing G2019S LRRK2 can be rescued through blocking the elevated mRNA translation observed in these animals. This work raises a number of exciting questions that we aim to tackle in future experiments: (i) How does the impact of mutant LRRK2 on translation lead to neuronal dysfunction and death? (ii) Does LRRK2 affect translation through other established regulatory pathways? (iii) Does the metabolic regulation of mRNA translation influence age-related dopamine neuron viability in accordance with its established effects on organismal aging?

From Martin et al., Journal of Neurochemistry, 2014 (diagram)
From Martin et al., Journal of Neurochemistry, 2014

Through these studies, we will expand on the established role of mRNA translation in aging to probe its contribution to age-related dopamine neuron loss and identify key pathogenic pathways underlying neuronal toxicity linked to LRRK2 kinase activity.


Martin, I., Abalde-Atristain, L., Kim, J.W., Dawson, T., Dawson, V.L. (2014) Aberrant Protein Synthesis in G2019S LRRK2 Drosophila Parkinson's Disease-Related Phenotypes. Fly, 8(3) 165-169.

Martin, I., Kim, J.W., Lee, B.D., Kang, H., Xu, J-C., Jia, H., Stankowski, J., Kim, M-S., Zhong, J., Kumar, M., Andrabi, S.A., Xiong, Y., Dickson, D.W., Wszolek, Z.K., Pandey, A., Dawson, T.M., Dawson, V.L. (2014) Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease. Cell, 157(2) 472-485.

Narayanasamy, S.K., Simpson, D.C., Martin, I., Grotewiel, M., Gronert, S. (2014) Paraquat exposure and Sod2 knockdown have dissimilar impacts on the Drosophila melanogaster carbonylated protein proteome. Proteomics, 14 (21) 2566-2577.

Martin, I., Dawson, V.L., Dawson, T.M. (2011) Recent advances in the genetics of Parkinson's disease. Annual Review of Genomics and Human Genetics, vol 22 p301-325.

Martin, I., Jones, M.A., Rhodenizer, D., Alaimo, J.T., Warrick, J.M., Seroude, L. and Grotewiel, M. (2009) Sod2 knock-down in the musculature has whole organism consequences in Drosophila. Free Radical Biology and Medicine 47(6) 803-813.

Martin, I., Jones, M.A. and Grotewiel M. (2009) Manipulation of Sod1 ubiquitously, but not in nervous system or muscle, impacts age-related parameters in Drosophila. FEBS Letters 583(13) 2308-2314.

Lab members

Vinita Chittoor, Ph.D., M.S.

Vinita Chittoor
Ph.D., University of Florida
M.S., Hislop School of Biotechnology, India
B.S., Bharatiya Vidya Bhavans, India

During my Masters in India, I had the opportunity to work on the development of multidrug resistance in invasive breast cancer tissues at the Indian Institute of Sciences (IISc). To gain further research experience I joined Dr. Pradeep Kumar's team at the Indian Institute of Technology (IIT, Bombay) to study the effects of chemically-modified siRNAs on the malarial parasite. With the chance to study such varied diseases, I realized that management of protein folding is key to maintaining cellular health. And to pursue this, I joined Dr. Notterpek's lab at the University of Florida and completed my PhD dissertation on the role of chaperones in preventing the misfolding of a Schwann cell myelin protein, PMP22. My study showed that HSP70 plays a crucial role in this and therefore targeting the chaperone pathway might be a plausible therapeutic option for the disease. With this interest in protein misfolding diseases, I joined Dr. Ian Martin's lab at OHSU where I work on evaluating the influence of diet on LRRK2-mediated toxicity in Parkinson's disease. We are specifically interested in testing the levels and types of amino acids which can modulate the neuronal toxicity in mutant LRRK2 carrying Drosophila melanogaster model for the disease.

Sierra Lavoy, B.A., outdoors, with dogs

Sierra Lavoy
B.A., Reed College

I attended a number of undergraduate universities including Pace University in New York City, and King's college in London, before receiving my BA in biology from Reed college in Portland, Oregon. While living in New York, I worked as a researcher, studying the effects of the secondary immune response glutathione and it's derivatives on the active and latent forms of attenuated tuberculosis, Bovis BCG. While attending Reed college I became entranced in neurology, and researched the effects of anti-malarial drugs on various receptors in the central nervous system by utilizing the NMDA-receptor mediated vocalization circuit of African clawed frogs as a diagnostic tool for off target effects, in my undergraduate thesis. I am thrilled to be joining the Martin lab, which works to define key pathogenic mechanisms underlying neurodegeneration in Parkinson's disease by investigating how disease-causing mutations impact neuronal function.