Faculty Members

Dr. Toshifumi Yokota

Professor
Department of Medical Genetics
    Contact details are for academic matters only.

About Me

The Friends of Garrett Cumming Research & Muscular Dystrophy Canada HM Toupin Neurological Science Endowed Research Chair

Yokota-lab Website:https://sites.google.com/ualberta.ca/yokota-lab

Toshifumi Yokota was born in Morioka and raised in several cities in Japan, including Chiba, Tsu, Yokohama, and Tokyo. He obtained his PhD degree from the University of Tokyo under the supervision of Dr. Shin'ichi Takeda, where he studied the regulation of muscle regeneration. Subsequent to doctoral studies, he moved to the Imperial College London (ICL), UK for postdoctoral training and worked with Dr. Terence Partridge. It was at that point that he became fascinated by antisense oligonucleotide-based therapy, an innovative therapeutic approach using short DNA-like molecules for the treatment of muscular dystrophy.

Currently, Dr. Yokota is a Professor at the Department of Medical Genetics, University of Alberta, holding the title of the Friends of Garrett Cumming Research & Muscular Dystrophy Canada HM Toupin Neurological Science Endowed Research Chair since 2011. His research goal is to discover, optimize, and translate novel therapies for neurological and musculoskeletal disorders. Specifically, his research aims to develop and apply new methods to correct genetic mutations in a precise manner. Examples of technologies include genome editing and synthetic antisense oligonucleotides. These new methods are applied to the correction of genetic mutations, new disease models, drug discovery, and addressing fundamental biological questions.



Research

https://sites.google.com/ualberta.ca/yokota-lab

Our overarching goal is to discover, optimize, and translate novel therapies for neurological and musculoskeletal disorders. We currently focus on following projects:

1. Antisense and Genome Editing Therapies

Antisense-mediated therapy is an exciting new approach to treating diseases using DNA-like molecules. These molecules, called antisense oligonucleotides, act like a stitch or Band-Aid to mitigate the effects of genetic mutations and restore the gene function. By utilizing integrative experimental and computational approaches, such as antisense oligonucleotides, CRISPR/Cas9 genome editing, and machine-learning, the focuses of our group are to develop novel personalized molecular therapies for neuromuscular and musculoskeletal diseases. Our focus is on several devastating genetic diseases, including Duchenne/Becker muscular dystrophy (DMD/BMD), dysferlin-deficient muscular dystrophy (limb-girdle muscular dystrophy type 2b, Miyoshi myopathy, and distal myopathy with anterior tibial onset), facioscapulohumeral muscular dystrophy (FSHD), spinal muscular atrophy (SMA), and fibrodysplasia ossificans progressiva (FOP).

2. Dystrophin Revertant Fibre Analysis

Duchenne muscular dystrophy (DMD) is one of the most common lethal genetic disorders, occurring once per 3,500 male births, caused by a lack of a protein called dystrophin. Interestingly, in many DMD patients and animal models, a small proportion of muscle fibres show strong dystrophin positive staining called "revertant fibres". We previously identified the mechanism by which revertant fibres arise from spontaneous exon skipping (alternative splicing) and proliferate through muscle regeneration with activation of muscle precursor (stem) cells. The aim of the current project is to elucidate the mechanisms underlying generation and proliferation of revertant fibres. By analyzing these fibres, researchers may be able to identify new and more effective targets for treatments of DMD.

3. Muscle Membrane Imaging

Some forms of muscular dystrophy patients including limb-girdle muscular dystrophy type 2B (LGMD2B), Miyoshi myopathy (MM), and distal myopathy with anterior tibial onset (DMAT) have a primary defect in skeletal muscle membrane repair. Their muscle fibres are unable to effectively repair the damaged muscle membrane. We analyze the molecular mechanisms involved in muscle membrane repair machinery with our state-of-the-art imaging infrastructure including multi-photon (two-photon) laser microscope. A better understanding of this process could lead to better treatments for patients. We are also developing antisense drugs to treat them.

4. Role of Water Channel Aquaporins in Muscle and Brain

A water channel Aquaporin-4 (AQP4) is known to selectively express in the fast-twitch skeletal muscle fibres and at the perivascular blood-brain-barrier (BBB) in the brain; however its physiological function remains poorly understood. In the past ten years, we have published several key findings related to the role of AQP4 in muscle fatigue and recovery using mutant mouse models. These include regulation of water flow across muscle membrane (sarcolemma) by AQP4 against osmotic changes and the recovery of muscle force generation after osmotic changes or exercise. The goal of our research program is to characterize the role of AQP4 in response to the muscle exercise and fatigue in muscles and brains.

Last updated: August 31, 2019

 

Research Keywords

Antisense oligonucleotides, CRISPR-Cas9, Gene Therapy, Gene-editing, Genetics, Muscle Pathology, Muscular dystrophy, Musculoskeletal Diseases, Neurology, Neuromuscular Disease, Neuroscience, Water Channel

Team Members

https://sites.google.com/ualberta.ca/yokota-lab/lab-members?authuser=0

Positions Available

The laboratory of Dr. Toshifumi Yokota invites applications for postdoc, undergraduate and graduate student positions. By utilizing integrative experimental and computational approaches, such as antisense oligonucleotides, CRISPR/Cas9, and machine-learning, the focuses of his group are to develop novel molecular therapies for neuromuscular and musculoskeletal diseases. These new methods are applied to the correction of genetic mutations, new disease models, drug discovery, and addressing fundamental biological questions. His group is actively collaborating with the world-class researchers and industry partners. The highly interdisciplinary and collaborative environment provides unique career development opportunities for trainees. His laboratory is renowned internationally for its work on the development of genome-editing/antisense technology as well as the studies on animal models. Full-time graduate students receive a stipend guaranteed to be equal to or greater than the minimum, determined yearly by the graduate committee. Priority will be given to those who want to further pursue PhD degree.

Representative original research publications of the PI with trainees since 2016 include; 

1.         Echigoya et al (2019) Mol Ther. In Press (IF=8.402)

2.         Lim et al (2019) Mol Ther. 27: 76-86

3.         Lee et al (2018) Mol Ther Nucleic Acids.13: 596-604 (IF=5.919)

4.         Lee et al (2018) PLoS ONE.13:e0197084 (IF=3.057)

5.         Echigoya et al (2017) PNAS. 114:4213-8 (IF=9.580)

6.         Echigoya et al (2017) Mol Ther. 25: 2561-2572

7.         Touznik et al (2017) Sci Rep. 7:3672 (IF=4.259) 

8.         Kamaludin et al (2016) Hum. Mol. Genet., 25(17):3798-3809.(IF=6.393)

9.         Rodrigues et al (2016) Sci. Rep., 6, 38371

 (trainees underlined)

Located in Edmonton, one of the sunniest cities in Canada, the Faculty has been internationally recognized as among the world’s top 50 medical schools and as one of Canada’s premier health-education institutions.  The University is currently home to 39,000 students and 15,000 faculty and staff.   

All applicants should have good spoken and written communication skills in English. Interested applicants should send i) a cover letter briefly describing your previous experience and your future research interest/plan, ii) a curriculum vitae, and iii) contact information of at least three references to Dr. Toshifumi Yokota.

Department of Medical Genetics https://www.ualberta.ca/medical-genetics

Maternal and Child Health Scholarship Program (MatCH Program) https://www.ualberta.ca/medicine/programs/maternal-and-child-health-scholarship-program

Neuroscience and Mental Health Institute (NMHI) https://www.ualberta.ca/neuroscience-and-mental-health-institute 

Last updated: October 10, 2019