Krembil Research Institute

Academic medical research institute in Toronto

Toronto Western Hospital's Krembil Neuroscience Centre

The Krembil Research Institute, formerly known as the Toronto Western Research Institute, is an academic medical research institute in Toronto. It is one of the largest research institutes in Canada focusing on human neurological disease.

Krembil is one of the principal research institutes of the University Health Network and is the research institute of the Toronto Western Hospital.

Krembil researches treatments for Alzheimer's disease, Parkinson's disease, epilepsy, stroke, brain tumours, concussions, spinal cord injuries, neuro-ophthalmologic and other ocular disorders, multiple sclerosis and autoimmune disorders.

## History

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In the early 1980s, Toronto Western took on additional neurological and neurosurgical care responsibilities for the UHN group. In 1980, the Playfair Neuroscience Institute was created. In 1999, it was renamed the Toronto Western Research Institute. The Institute added research areas in ophthalmology, rheumatology and orthopaedics. By 2004, under the founding leadership of neurosurgeon 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 from the Krembil family. In 2013, the Krembil Discovery Tower opened at Toronto Western.

## Research Activities

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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.[citation needed]

In September 2021, Krembil took ownership of the World Community Grid from IBM.[2]

## Krembil and UHN Neuroscience achievements

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* 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)[3]
* First in world to show the reversibility of brain shrinkage and dysfunction from alcoholism with abstinence. (P. Carlen, 1978)[4]
* Showed genetic predisposition to developing Reflex Sympathetic Dystrophy. (A. Mailis, 1994)[5]
* Performed the first deep brain stimulation in Canada to effectively control Parkinson's symptoms. (A. Lozano, 1994),[6][7]
* Awake craniotomy with same day discharge for brain tumor removal using image guided approach. (M. Bernstein, 1996)[8]
* Identified genes responsible for hereditary blindness, Alzheimer's, ALS and Huntington's disease. (P. St. George Hyslop, 1990s),[9][10][11]
* 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)[12]
* Identified the individual brain cells that control pain. (K. Davis and A. Lozano, 1998)[13]
* Identified of protein that triggers autoimmune response in Sjögren's syndrome, as well as a vaccine to treat the condition. (A. Bookman, 2002)[14]
* Developed method for detecting gene mutations that enhance care for families with retinoblastoma. (B. Gallie, 2003)[15]
* Performed the world's first deep brain stimulation for treatment resistant depression. (A. Lozano & S. Kennedy, 2003)[16]
* Neural adult stem cell transplantation findings show promising results in repairing spinal cord damage and restoring mobility in rats. (M. Fehlings & S. Karimi, 2006)[17]
* Performed the world's first deep brain stimulation for treatment of Alzheimer's Disease (A. Lozano, 2012),[18][19]
* Development of new experimental drug for the neuroprotectant treatment of stroke (M. Tymianski, 2012)[20]

## Krembil Directors

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* 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)
* 2013–2022 – Donald F. Weaver
* 2022–present – Jaideep Bains

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.[21] [22]

## Facilities

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Krembil occupies 105,000 sq ft (9,800 m2) at Toronto Western Hospital for basic science, clinical, imaging and epidemiological research. 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 2013, Krembil expanded into an additional 325,000 sq ft (30,200 m2) of space, spanning nine floors, in the Krembil Discovery Tower. The Tower space includes 150,000 sq ft (14,000 m2) of "wet" laboratory bench space for Krembil basic science researchers.

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 at Krembil. The campaign had raised over $273 million as of January 2016.

## Strategic research alliances

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

* 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

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1. ^ a b Rutka, J. T.; Wallace, C (2010). "Excellence in neurosurgery program building: Enhancing the academic mission". Clinical Neurosurgery. 57: 100–11\. PMID 21280502.
2. ^ "World Community Grid finds a new home at Krembil Research Institute". www.worldcommunitygrid.org. Archived from the original on 2021-09-13. Retrieved 2021-09-13.
3. ^ 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.
4. ^ 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.
5. ^ 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. S2CID 22469520.
6. ^ 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.
7. ^ Castrioto, Anna; Lozano, A. M.; Poon, Y. Y.; Lang, A. E.; Fallis, M; Moro, E (2011). "Ten-Year Outcome of Subthalamic Stimulation in Parkinson Disease". Archives of Neurology. 68 (12): 1550–6\. doi:10.1001/archneurol.2011.182. PMID 21825213.
8. ^ Bernstein, Mark (1996). "Brain tumour surgery in the elderly: A brief reappraisal". Canadian Journal of Surgery. 39 (2): 147–50\. PMC 3949854. PMID 8769926.
9. ^ 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): 1–7\. Bibcode:2000NYASA.924....1S. doi:10.1111/j.1749-6632.2000.tb05552.x. PMID 11193785. S2CID 13054535.
10. ^ 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. S2CID 4308372.
11. ^ 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. Bibcode:1994Sci...263..537S. doi:10.1126/science.8290965. PMID 8290965.
12. ^ 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.
13. ^ 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. S2CID 22329600.
14. ^ 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. S2CID 22039999.
15. ^ 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.
16. ^ 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.
17. ^ 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. PMC 6673854. PMID 16571744.
18. ^ 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.
19. ^ 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.
20. ^ 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.
21. ^ "Peter St George-Hyslop — Cambridge Institute for Medical Research". 1 April 2019. Archived from the original on 1 April 2019. Retrieved 18 January 2022.
22. ^ "Krembil Welcomes New Director | UHN Research".

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