L Sanders headshot
Principal Investigator
Associate Professor in Neurology
Associate Professor of Pathology
Member of the Duke Cancer Institute
Member in the Duke Clinical Research Institute
Contact Information

Office: 
5128 Medical Sciences Research Building III

Campus mail: 
3 Genome Court, Durham, NC 27710

Email: 
Laurie.Sanders@duke.edu

Sanders Igniting Innovations

About us

The Sanders lab studies Parkinson’s disease (PD), the most common neurodegenerative movement disorder. Even with expert treatment, PD patients typically deteriorate over time and endure considerable motor and non-motor disability. There are no disease modifying therapies, thus, this is an urgent unmet medical need. We take a translational approach (i.e. bench-to-bedside), aiming to translate our multidisciplinary basic scientific research into meaningful health outcomes for PD patients. To do so, we combine all levels of analysis, from neurons in a dish to human studies. We have adapted, developed, and are continuing to create and apply novel methods and technology for PD mechanistic investigation. Our primary focus is on the role of genome integrity and DNA repair in the pathogenesis of PD.

We were the first to show that LRRK2 G2019S mutation carriers have increased mitochondrial DNA (mtDNA) damage using human induced pluripotent stem cells (iPSC)-derived neural cells (Sanders et al 2014). Further, the mtDNA damage phenotype was shown to be caused by the LRRK2 mutations. When the mutations were “corrected” using zinc finger nuclease (ZFN)-mediated gene editing, levels of mtDNA damage returned to that of basal control levels. Thus, the mtDNA damage phenotype can be unambiguously attributed to the LRRK2 G2019S mutation. This new link between LRRK2 and mtDNA damage opens up an entirely original line of investigation into the pathogenic mechanisms of LRRK2-related PD. Our current work focuses on the underlying mechanisms of LRRK2-induced mtDNA damage, dysfunction and neurodegeneration.

We also found selective mtDNA damage as a molecular marker of vulnerable nigral neurons in sporadic PD. We are able to detect mitochondrial abasic sites (with brain region and cell type specificity) in multiple pre-clinical models of PD and in human PD postmortem brain tissue (Sanders et al 2014). We are interested in pursuing the underlying DNA repair defect in PD and applying novel therapeutic approaches targeting genome integrity.

There are no peripheral biomarkers for PD. The identification and validation of high throughput biomarkers to measure disease progression (as well as identify pre-clinical disease onset) is critical to the development of disease-modifying or even preventative therapies. We are investigating and defining peripheral biomarkers for PD.

Recent Publications

Sastre D, Zafar F, Torres CAM, Piper D, Kirik D, Sanders LH, Qi S, Schüle B. Nuclease-dead S. aureus Cas9 downregulates alpha-synuclein and reduces mtDNA damage and oxidative stress levels in patient-derived stem cell model of Parkinson's disease. bioRxiv [Preprint]. 2023 Jan 24:2023.01.24.525105. doi: 10.1101/2023.01.24.525105. PMID: 36747875; PMCID: PMC9900844.
 
Miner, Kristin M., Anuj S. Jamenis, Tarun N. Bhatia, Rachel N. Clark, Dhivyaa Rajasundaram, Sylvie Sauvaigo, Daniel M. Mason, et al. “α-synucleinopathy exerts sex-dimorphic effects on the multipurpose DNA repair/redox protein APE1 in mice and humans.Prog Neurobiol 216 (September 2022): 102307. https://doi.org/10.1016/j.pneurobio.2022.102307.
 
Miner, K. M., T. N. Bhatia, A. S. Jamenis, R. N. Clark, N. Abraham, D. Rajasundaram, S. Sauvaigo, et al. “A Connection Between DNA Repair Protein APE1, Alpha-Synucleinopathy, and Biological Sex in Rodents and Humans.” Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology 36 (May 1, 2022). https://doi.org/10.1096/fasebj.2022.36.S1.R3221.
 
Hao, Nanjing, Zeyu Wang, Pengzhan Liu, Ryan Becker, Shujie Yang, Kaichun Yang, Zhichao Pei, et al. “Acoustofluidic multimodal diagnostic system for Alzheimer's disease.Biosens Bioelectron 196 (January 15, 2022): 113730. https://doi.org/10.1016/j.bios.2021.113730.
 
Kakar, Rumit S., Johanne V. Pastor, Orson W. Moe, Fabrisia Ambrosio, Danielle Castaldi, and Laurie H. Sanders. “Peripheral Klotho and Parkinson's Disease.Mov Disord 36, no. 5 (May 2021): 1274–76. https://doi.org/10.1002/mds.28530.
 
Gonzalez-Hunt, Claudia P., and Laurie H. Sanders. “DNA damage and repair in Parkinson's disease: Recent advances and new opportunities.J Neurosci Res 99, no. 1 (January 2021): 180–89. https://doi.org/10.1002/jnr.24592.
 
Parrilla Castellar, Edgardo R., Jennifer K. Plichta, Richard Davis, Claudia Gonzalez-Hunt, and Laurie H. Sanders. “Somatic Mutations in LRRK2 Identify a Subset of Invasive Mammary Carcinomas Associated with High Mutation Burden.Am J Pathol 190, no. 12 (December 2020): 2478–82. https://doi.org/10.1016/j.ajpath.2020.08.010.
 
Gonzalez-Hunt, C. P., E. A. Thacker, C. M. Toste, S. Boularand, S. Deprets, L. Dubois, and L. H. Sanders. “Mitochondrial DNA damage as a potential biomarker of LRRK2 kinase activity in LRRK2 Parkinson's disease.Sci Rep 10, no. 1 (October 14, 2020): 17293. https://doi.org/10.1038/s41598-020-74195-6.
 
Sanders, Laurie H., and Nicole Calakos. “Dopamine Metabolism May Have Unexpected Benefits for Mitochondrial Energy Production.Mov Disord 35, no. 4 (April 2020): 562. https://doi.org/10.1002/mds.28005.
 
Sahu, A., H. Mamiya, S. N. Shinde, A. Cheikhi, L. L. Winter, N. V. Vo, D. Stolz, et al. “Age-related declines in α-Klotho drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration.Nat Commun 9, no. 1 (November 19, 2018): 4859. https://doi.org/10.1038/s41467-018-07253-3.
 
Van Laar, Victor S., Beth Arnold, Evan H. Howlett, Michael J. Calderon, Claudette M. St Croix, J Timothy Greenamyre, Laurie H. Sanders, and Sarah B. Berman. “Evidence for Compartmentalized Axonal Mitochondrial Biogenesis: Mitochondrial DNA Replication Increases in Distal Axons As an Early Response to Parkinson's Disease-Relevant Stress.J Neurosci 38, no. 34 (August 22, 2018): 7505–15. https://doi.org/10.1523/JNEUROSCI.0541-18.2018.

 

Read a complete list of Dr. Sanders' publications on PubMed.

Our Team

Research Associate, Senior
Research Technician II
Postdoctoral Associate
Research Technician II
Lab Technician I
Graduate Student
Research Technician II
Graduate Student
Graduate Student
Undergraduate Research Assistant
Undergraduate Research Assistant
Undergraduate Research Assistant
Undergraduate Research Assistant
Undergraduate Research Assistant

Career Opportunities

The Sanders group is always looking for interested, talented members for our team. Please email Dr Sanders at laurie.sanders@duke.edu to learn more about open positions.