Krembil Research Institute

Toronto Western Hospital's Krembil Neuroscience Centre.

The Krembil Research Institute (Krembil), formerly known as the Toronto Western Research Institute, is a non-profit academic medical research institute located in Canada's largest city, Toronto. The Krembil is one the principal research institutes of the University Health Network of academic teaching hospitals associated with the University of Toronto; the Krembil is also one of the largest research institutes in Canada focusing on human neurological disease from both a basic science and clinical research perspective. Research within the Krembil is directed at the development of treatments for neurodegenerative diseases (Alzheimer's disease, Parkinson's disease), epilepsy, stroke, brain tumours, concussions, spinal cord injuries, neurophthalmologic and other ocular disorders, multiple sclerosis and autoimmune disorders.

The University Health Network (UHN) is Canada's largest academic medical centre, comprising four major teaching hospitals (Toronto Western Hospital, Toronto General Hospital, Princess Margaret Cancer Centre, Toronto Rehabilitation Institute) and a strategic alliance with the Toronto Mount Sinai Hospital. The Krembil is the research institute of the Toronto Western Hospital and fulfills the mandate for neuroscience (including ophthalmology) and musculoskeletal health research within the UHN academic medical centre. In total, UHN devotes C$160 million a year to research and trains more than 3,200 undergraduate, graduate and medical students at its member hospitals and institutes in association with the University of Toronto. The University of Toronto is Canada's largest university and one of the biggest in North America, consistently ranking in the top 25 universities internationally in the Times Higher Education World University Rankings, the Academic Ranking of World Universities and the QS World University Rankings.

History

In 1895, twelve physicians in the west end of Toronto united to create the Toronto Western Hospital (TWH, or the "Western") in order to serve an overlooked culturally-diverse neighbourhood in Toronto. The Toronto Western Hospital first opened as a medication dispensary, followed by a 30-bed general hospital temporarily functioning out of two rented houses. By 1899 sufficient money was raised to purchase a nearby farmhouse and to build the Western on its present site. During construction, patients were treated year-round under large tents until the hospital officially opened in 1905. Throughout the 20th century, the Toronto Western Hospital functioned as a general hospital serving clients from culturally- and economically-diverse backgrounds. In the early 1980s, the Western took on additional neurological and neurosurgical care responsibilities for the UHN group of hospitals. Concomitant with this new clinical care focus, strength in applied neuroscience research began to emerge. In 1980, the Playfair Neuroscience Institute was created at the TWH to capitalize on this evolving neuroscience focus. In 1999, the Playfair Neuroscience Institute was renamed the Toronto Western Research Institute as it joined the Toronto General Research Institute and the Princess Margaret Research Institute as the three main hospital-based institutes within UHN. After this change, the Krembil also took on additional areas of research interest including ophthalmology, rheumatology and orthopaedics. By 2004, under the founding leadership of neurosurgeon Dr. C. Wallace, the Krembil had emerged as one of the largest research institutes in Canada with a neuroscience emphasis.^[1]

On November 13, 2015, the Krembil took on its current name. Prior to November 13, 2015, the Krembil was known as the Toronto Western Research Institute. The new name honours a family who knows the importance of giving. The Krembils are among Canada's leading investors in neuroscience research. Their impact at Toronto Western alone is $80 million, including the nine-storey, state-of-the-art Krembil Discovery Tower, which opened in 2013.

Research Activities

Krembil scientists are at work on a diverse array of human healthcare questions within multiple research programs. At the Krembil, neuroscientists explore the function of the nervous system as they develop treatments for neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, epilepsy, spinal cord injuries, cerebral ischemia (stroke), vascular brain malformations, aneurysms, brain tumours and pain disorders. The Krembil is also home to the Vision Science Research Program, a joint UHN/University of Toronto Program. This research is directed into the following areas: molecular genetics of blinding eye diseases with brain disorders; treatment and biophysics of glaucoma; eye movement control mechanisms; neuronal damage; retinal degeneration and diabetic retinopathy. Arthritis and associated rheumatological degenerative diseases are the focus of the researchers in the musculoskeletal research program at the Krembil as part of the UHN Arthritis and Autoimmunity Research Centre. Their investigations are aimed at revealing the causes of, and generating therapies for, these autoimmune and orthopaedic ailments.

Historical Research Achievements of the Krembil and UHN Neuroscience

• First in world to describe Progressive Supranuclear Palsy (PSP; Steele-Richardson-Olszewski Syndrome) as a unique form of dementia and neurodegenerative disease involving the gradual deterioration and death of specific volumes of the brain (J. Steele, J. Richardson & J. Olszewski, 1963)^[2]
• First in the world to show the reversibility of brain shrinkage and dysfunction from alcoholism with abstinence. (P. Carlen, 1978)^[3]
• Showed genetic predisposition to developing Reflex Sympathetic Dystrophy. (A. Mailis, 1994)^[4]
• Performed the first deep brain stimulation in Canada to effectively control Parkinson's symptoms. (A. Lozano, 1994),^[5][6]
• Awake craniotomy with same day discharge for brain tumor removal using image guided approach. (M. Bernstein, 1996)^[7]
• Identified genes responsible for hereditary blindness, Alzheimer's, Lou Gehrig's and Huntington's disease. (P. St. George Hyslop, 1990's),^[8][9][10]
• First in Canada to use Image-Guided Minimally Invasive Therapy (IGMIT) during surgery allowing for real-time magnetic resonance imaging to guide surgeons to the location of a brain tumor. (M. Bernstein, 1998)^[11]
• Identified the individual brain cells that control pain. (K. Davis and A. Lozano, 1998)^[12]
• Identified of protein that triggers autoimmune response in Sjögren's syndrome, as well as a vaccine to treat the condition. (A. Bookman, 2002)^[13]
• Developed method for detecting gene mutations that enhance care for families with retinoblastoma. (B. Gallie, 2003)^[14]
• Performed the world's first deep brain stimulation for treatment resistant depression. (A. Lozano & S. Kennedy, 2003)^[15]
• Neural adult stem cell transplantation findings show promising results in repairing spinal cord damage and restoring mobility in rats. (M. Fehlings & S. Karimi, 2006)^[16]
• Performed the world's first deep brain stimulation for treatment of Alzheimer's Disease (A. Lozano, 2012),^[17][18]
• Development of new experimental drug for the neuroprotectant treatment of stroke (M. Tymianski, 2012)^[19]

The Krembil Directors

1980-1988 – William Tatton

1988-1990 – Charles Tator (interim)

1990-1999 – Peter Carlen

1999-2004 – Christopher Wallace

2004-2011 – Peter St George-Hyslop

2011-2013 – Peter Carlen (interim)

2013–present – Donald Weaver

Christopher Wallace MD, MSc, FRCSC, a neurosurgeon and neurophysiologist, was the first official director of the Krembil; his research focussed on therapeutic approaches to vascular brain injury.^[1] Peter St George-Hyslop MD, PhD, FRCPC, a neurologist and PhD geneticist, was the second full-time director of the Krembil; his research focussed on the genetic basis of neurodegenerative diseases such as Alzheimer's dementia.^[20]

Facilities

Since its inception, the Krembil has been co-located with the Toronto Western Hospital at the corner of Bathurst Street and Dundas Street West in Toronto, Canada. Within this location, the Krembil occupies 105,000 sq ft (9,800 m²) dedicated to a full range of basic science, clinical, imaging and epidemiological research. In 2013, the Krembil expands into an additional 325,000 sq ft (30,200 m²) of space, spanning nine floors, in the newly constructed Krembil Discovery Centre attached to the TWH. The Krembil Discovery Centre space includes 150,000 sq ft (14,000 m²) of "wet" laboratory bench space for Krembil basic science researchers.

In 2011, the Krembil was home to 122 biomedical researchers, 206 technical/support staff and 157 research trainees, who collectively produced 515 peer-reviewed publications supported by more than $43,612,000 of external research funding.

In addition to conventional peer-review funding, the Krembil receives support from the Toronto General/Toronto Western Hospital Foundation which is currently embarked upon a $200 million "Brain Campaign" to support neuroscience research within the Krembil.

Strategic Research Alliances

The Krembil has many strategic research alliances, nationally and internationally, to facilitate and enhance the delivery of its research mandate. Two of the notable strategic research alliances are as follows:

• The Tanz Centre for Research in Neurodegenerative Diseases (Tanz CRND) is a research institute at the University of Toronto, under the umbrella of the Faculty of Medicine, with a focus on the spectrum of neurodegenerative diseases.
• Toronto Dementia Research Alliance (TDRA) is a Toronto-wide network of researchers focused on the understanding and treatment of all forms of dementia.

References

1. Rutka, J. T.; Wallace, C (2010). "Excellence in neurosurgery program building: Enhancing the academic mission". Clinical neurosurgery. 57: 100–11. PMID 21280502.
2. Richardson, J. C.; Steele, J; Olszewski, J (1963). "Supranuclear Ophthalmoplegia, Pseudobulbar Palsy, Nuchal Dystonia and Dementia. A Clinical Report on Eight Cases of 'heterogenous System Degeneration'". Transactions of the American Neurological Association. 88: 25–9. PMID 14272249.
3. Carlen, P.; Wortzman, G; Holgate, R.; Wilkinson, D.; Rankin, J. (1978). "Reversible cerebral atrophy in recently abstinent chronic alcoholics measured by computed tomography scans". Science. 200 (4345): 1076–8. Bibcode:1978Sci...200.1076C. doi:10.1126/science.653357. PMID 653357.
4. Mailis, A; Wade, J (1994). "Profile of Caucasian women with possible genetic predisposition to reflex sympathetic dystrophy: A pilot study". The Clinical Journal of Pain. 10 (3): 210–7. doi:10.1097/00002508-199409000-00007. PMID 7833579.
5. Ponce, F. A.; Lozano, A. M. (2011). "The surgical management of Parkinson's disease". CNS & Neurological Disorders Drug Targets. 10 (6): 685–92. doi:10.2174/187152711797247795. PMID 21838672.
6. Castrioto, Anna; Lozano, A. M.; Poon, Y. Y.; Lang, A. E.; Fallis, M; Moro, E (2011). "Ten-Year Outcome of Subthalamic Stimulation in Parkinson Diseas e". Archives of Neurology. 68 (12): 1550–6. doi:10.1001/archneurol.2011.182. PMID 21825213.
7. Bernstein, Mark (1996). "Brain tumour surgery in the elderly: A brief reappraisal". Canadian Journal of Surgery. 39 (2): 147–50. PMC 3949854. PMID 8769926.
8. St George-Hyslop, P. H. (2006). "Genetic Factors in the Genesis of Alzheimer's Disease". Annals of the New York Academy of Sciences. 924: 1–7. Bibcode:2000NYASA.924....1S. doi:10.1111/j.1749-6632.2000.tb05552.x. PMID 11193785.
9. Sherrington, R; Rogaev, E. I.; Liang, Y; Rogaeva, E. A.; Levesque, G; Ikeda, M; Chi, H; Lin, C; Li, G; Holman, K; Tsuda, T; Mar, L; Foncin, J. F.; Bruni, A. C.; Montesi, M. P.; Sorbi, S; Rainero, I; Pinessi, L; Nee, L; Chumakov, I; Pollen, D; Brookes, A; Sanseau, P; Polinsky, R. J.; Wasco, W; Da Silva, H. A.; Haines, J. L.; Perkicak-Vance, M. A.; Tanzi, R. E.; et al. (1995). "Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease". Nature. 375 (6534): 754–60. Bibcode:1995Natur.375..754S. doi:10.1038/375754a0. PMID 7596406.
10. St George-Hyslop, P; McLachlan, D. C.; Tsuda, T; Rogaev, E; Karlinsky, H; Lippa, C. F.; Pollen, D (1994). "Alzheimer's disease and possible gene interaction". Science. 263 (5146): 537. doi:10.1126/science.8290965. PMID 8290965.
11. Bernstein, Mark; Al-Anazi, Abdul Rahman; Kucharczyk, Walter; Manninen, Pirjo; Bronskill, Michael; Henkelman, Mark (2000). "Brain tumor surgery with the Toronto open magnetic resonance imaging system: Preliminary results for 36 patients and analysis of advantages, disadvantages, and future prospects". Neurosurgery. 46 (4): 900–7; discussion 907–9. doi:10.1097/00006123-200004000-00023. PMID 10764263.
12. Davis, K. D.; Lozano, A. M.; Tasker, R. R.; Dostrovsky, J. O. (1998). "Brain targets for pain control". Stereotactic and Functional Neurosurgery. 71 (4): 173–9. doi:10.1159/000029661. PMID 10461103.
13. Winer, Shawn; Astsaturov, Igor; Cheung, Roy; Tsui, Hubert; Song, Aihua; Gaedigk, Roger; Winer, Daniel; Sampson, Anastasia; McKerlie, Colin; Bookman, Arthur; Dosch, H-Michael (2002). "Primary Sjögren's syndrome and deficiency of ICA69". The Lancet. 360 (9339): 1063–9. doi:10.1016/S0140-6736(02)11144-5. PMID 12383988.
14. Richter, Suzanne; Vandezande, Kirk; Chen, Ning; Zhang, Katherine; Sutherland, Joanne; Anderson, Julie; Han, Liping; Panton, Rachel; Branco, Patricia; Gallie, Brenda (2003). "Sensitive and Efficient Detection of RB1 Gene Mutations Enhances Care for Families with Retinoblastoma". The American Journal of Human Genetics. 72 (2): 253–69. doi:10.1086/345651. PMC 379221. PMID 12541220.
15. Kennedy, Sidney H.; Giacobbe, P; Rizvi, S. J.; Placenza, F. M.; Nishikawa, Y; Mayberg, H. S.; Lozano, A. M. (2011). "Deep Brain Stimulation for Treatment-Resistant Depression: Follow-Up After 3 to 6 Years". American Journal of Psychiatry. 168 (5): 502–10. doi:10.1176/appi.ajp.2010.10081187. PMID 21285143.
16. Karimi-Abdolrezaee, S.; Eftekharpour, E; Wang, J; Morshead, C. M.; Fehlings, M. G. (29 March 2006). "Delayed Transplantation of Adult Neural Precursor Cells Promotes Remyelination and Functional Neurological Recovery after Spinal Cord Injury". Journal of Neuroscience. 26 (13): 3377–89. doi:10.1523/JNEUROSCI.4184-05.2006. PMID 16571744.
17. Laxton, A. W.; Sankar, T; Lozano, A. M.; Hamani, C (2012). "Deep brain stimulation effects on memory". Journal of Neurosurgical Sciences. 56 (4): 341–4. PMID 23111294.
18. Smith, Gwenn S.; Laxton, Adrian W.; Tang-Wai, David F.; McAndrews, Mary Pat; Diaconescu, Andreea Oliviana; Workman, Clifford I.; Lozano, Andres M. (2012). "Increased Cerebral Metabolism After 1 Year of Deep Brain Stimulation in Alzheimer Disease". Archives of Neurology. 69 (9): 1141–8. doi:10.1001/archneurol.2012.590. PMID 22566505.
19. Kingwell, Katie (2012). "Stroke: Neuroprotection for patients with stroke moves one step closer to the clinic". Nature Reviews Neurology. 8 (4): 178. doi:10.1038/nrneurol.2012.44. PMID 22430113.
20. http://www.cimr.cam.ac.uk/investigators/st-george-hyslop/index.html[]

External links

• Toronto Western Research Institute
• Toronto Western Hospital
• University Health Network
• Faculty of Medicine, University of Toronto

Coordinates: 43°39′12″N 79°24′20″W / 43.65338°N 79.40563°W