Net Results EXPRESS (NRx) is an award-winning, monthly e-newsletter highlighting medical and scientific breakthroughs, major grants and honours awarded, and other research-related events at UHN. In this special issue, you can read about selected research accomplishments and milestones of the past year of our five research institutes, the Ontario Cancer Institute (OCI), the Toronto General Research Institute (TGRI), the Toronto Western Research Institute (TWRI), the Toronto Rehabilitation Institute (TRI) and the Techna Institute for the Advancement of Technology for Health (Techna).

We hope you will find this newsletter informative and helpful and we wish you a festive holiday season. If you have feedback or questions, please contact www@uhnresearch.ca.

Christopher J. Paige, PhD, FCAHS
Vice President, Research
UHN

Leukemia: Uncovering Genetic Diversity in Propagating Cells

UHN’s Dr. John Dick demonstrated that defective genes and the individual leukemia cells that carry them are organized in a more complex way than previously thought. The research team found that the leukemia cells taken from patients with acute lymphoblastic leukemia are actually composed of multiple families of genetically distinct leukemia cells. They discovered that the cells that propagate the disease and potentially survive therapy persist through generations, and even branch off and evolve to form genetically distinct cancer families. The findings challenge the conventional view that cancer progresses as a linear series of genetic events and that all the cells in a tumour share the same genetic abnormalities and growth properties. [Abstract]

Parkinson's Disease: New Insights into the Role of the Cerebellum in Disease Development

New findings from Drs. Robert Chen and Anthony Lang at TWRI have shed new light on our understanding of the role of the cerebellothalamocortical (CTC) pathway in Parkinson's disease (PD). The group assessed whether stimulation of the cerebellum or primary motor cortex is involved in the generation or transmission of tremors in PD. Their findings show that resting and postural tremors in PD are mediated by different neuronal pathways, and that the CTC pathway is involved in the generation or transmission of postural tremor. [Abstract]

Depression: Deep Brain Stimulation Shows Benefit in 3 and 6 Year Follow-Up Study

At least 30 percent of patients with depression are resistant to treatment with antidepressants. A study from TWRI’s Dr. Andres Lozano and UHN’s Psychiatrist-in-Chief, Dr. Sidney Kennedy, confirms that deep brain stimulation—the placement of electrodes at specific sites in the brain to deliver continuous stimulation—provides benefits in long-term treatment-resistant depression for as long as six years. [Abstract]

Regenerative Medicine: Development of Heart Cells from Stem Cells

A study from OCI’s Dr. Gordon Keller demonstrated the delicate balance of factors involved in producing heart cells from different types of embryonic and induced pluripotent stem cells. The study described the manipulation of key signalling pathways in pluripotent cells, which induced the differentiation of heart cell progenitors. These findings provide immense opportunities to develop novel therapies for cardiovascular disease, and to study the development of normal and diseased heart tissue. [Abstract]

Cancer: Novel Organic Nanoparticles for Cancer Targeting and Treatment

Findings from OCI’s Dr. Gang Zheng reported the creation of a biodegradable nanoparticle (called a 'porphysome')—a tiny particle with novel properties—that was made of the natural pigment porphyrin. The organic nature of these particles allows them to be loaded with dyes or drugs for use in therapy or medical imaging. "We got the components from nature" says Dr. Zheng. "The porphyrin is from algae that you can actually find in a health food store." [Abstract]

Respiratory Disease: Long-Term Study on the Effects of Acute Illness

A detailed study from TGRI investigators Drs. Margaret Herridge and Angela Cheung examined the long-term effects of Acute Respiratory Distress Syndrome (ARDS). The group conducted a five year study on the physical function and quality of life of patients with ARDS who were discharged from intensive care units. In general, these patients had a decreased ability to exercise, a reduction in overall quality of life and suffered from a number of psychological disorders, including depression and anxiety. [Abstract]

Lung Transplantation: High-Risk Donor Lungs Can Now Be Safely Used for Transplant

A TGRI team, led by Dr. Shaf Keshavjee, has shown in a clinical trial that the Toronto XVIVO Lung Perfusion System can safely and effectively treat, re-assess and improve the function of high-risk donor lungs so that they can be successfully transplanted into patients. This technique, developed by Dr. Keshavjee and his team at UHN, could significantly expand the donor organ pool and improve outcomes after transplantation. [Abstract]

Neurology: Surgical Procedure Reverses Loss of Brain Matter

Researchers at TWRI, led by Dr. Michael Tymianski, demonstrated the restoration of lost brain tissue through cranial bypass surgery. This surgical procedure restored blood flow to areas of the brain that undergo a progressive loss of tissue in cerebrovascular disease. Loss of brain tissue is associated with a higher risk of stroke, and the development of neurodegenerative disorders. These findings show, for the first time, the reversing of damaging effects of decreased blood flow to the brain. [Abstract]

Leukemia: Helping the Immune System Fight Cancer

Patients suffering from acute myeloid leukemia (AML) often experience recurrence of the disease due to incomplete elimination of all leukemic cells. TGRI’s Dr. Li Zhang developed a new method of treating AML by increasing the number of immune cells involved in the body’s defense against cancer, known as double negative T cells. This expansion of the immune system serves to increase the ability of a patient to combat AML. [Abstract]

Parkinson’s Disease: Enhancing the Therapeutic Benefits of L-DOPA

A study from TWRI’s Dr. Jonathan Brotchie, examined how different forms, R- or S-form, of MDMA (3,4-methylenedioxymethamphetamine) function to enhance the positive therapeutic effects of L-DOPA, the most common treatment for Parkinson's disease (PD). Addition of R-MDMA to L-DOPA treatment decreased the severity of dyskinesia, a motor complication associated with L-DOPA therapy, without altering the duration of antiparkinsonian effects. Addition of S-MDMA to LOPDA increased the duration of antiparkinsonian benefits although it exacerbated the following dyskinesia. [Abstract]

Neurology: Stimulation of the Motor Cortex Improves Hand Tremors

TWRI’s Drs. Elena Moro and Andres Lozano conducted a study to explore whether tremor symptoms of movement disorders could be improved through electrical stimulation of the brain. The group implanted electrodes above the motor cortex—the region of the brain involved in motor function—in patients with essential tremor (ET) and Parkinson’s disease (PD) and examined the effect of varying degrees of electrical stimulation on the severity of hand tremor. The study found that stimulation led to decreased hand tremor in patients with ET. PD patients, however, did not show signs of improvement. [Abstract]

Gastroenterology: New Insights into Blood Glucose Regulation

A study from TGRI’s Dr. Tony Lam examined the role of protein kinase C (PKC), a multi-functional enzyme located in the lining of the gut, in nutrient sensing—the ability of cells to recognize and respond to energy substrates, like glucose. The study found that PKC triggers the role of the gut in sensing available nutrients and maintains blood glucose levels. Activation of this system in the gut could potentially help to balance blood glucose levels in diabetes and obesity. [Abstract]

Autoimmune Diseases: Explaining the Role of PTPN22 in Immunity

TGRI’s Dr. Katherine Siminovitch identified a mechanism by which a mutation in the PTPN22 gene causes abnormal immune responses that lead to the development of autoimmune disease. This mutation caused a decrease in the PTPN22 gene’s protein product, Lyp, and led to an abnormal increase in the activation of three key immune cell populations: T-, B- and dendritic cells, a key feature of autoimmune disease. [Abstract]

Immunity: Identifying the Mechanisms Involved in Inflammation of the Colon

The causes of Inflammatory Bowel Disease (IBD)—a group of inflammatory conditions that affect the colon and small intestine, including ulcerative colitis (UC) and Crohn’s disease–remain unknown. A study from Dr. Tak Mak characterized a series of molecular events, involving Secretory Leukocyte Peptidase Inhibitor (SLPI) as a critical component in the healing and recovery of inflamed tissue in IBD. Treatment of mice suffering from ulcerative colitis with a synthetic form of SLPI was found to improve tolerance of the disease and decrease the incidence of death. [Abstract]

Pulmonary Disease: Increasing Physical Activity

TRI’s Dr. Dina Brooks has identified specific therapies, the six-minute walk test and the incremental shuttle walk test, that increase physical activity in patients with Chronic Obstructive Pulmonary Disease (COPD). COPD is a condition where lung function (and physical activity by consequence) is impaired due to obstruction of the airways. These findings provide clinicians with a targeted approach to implement therapies that increase physical activity. [Abstract]

Cancer: Creating a Blueprint of Protein Modifications

Protein-tyrosine phosphatases (PTPs) are a family of proteins that serve as critical regulators of cell growth. Oxidation—a modification that occurs when proteins interact with chemically reactive molecules containing oxygen—is known to inactivate PTP proteins, and is linked with cancer. OCI Director Dr. Ben Neel developed a profile of oxidized PTPs in a number of different human cancers and provided a "blueprint" of the different PTPs that regulate cellular processes important for the development of cancer. [Abstract]

Clinical Trials: The Impact of Announcements on Company Stock Prices

A study from TGRI’s Dr. Allan Detsky has examined the effect of positive and negative outcomes on company stock prices. The study identified 23 positive and 36 negative Phase III trials and analyzed the stock prices of the companies before and after a public announcement of trial results. Companies that reported positive results tended to see increases in their stock price before those results were publicly announced, suggesting a possibility of insider trading. These findings emphasize the potential legal and ethical considerations when divulging nonpublic information regarding clinical trials. [Abstract]

Prostate Cancer: Combination Treatment Greatly Improves Survival

A study from OCI’s Dr. Padraig Warde proposed a more effective method of treating advanced prostate cancer with a combination of radiation and hormone therapy. Combination therapy was found to improve survival by 23 percent and disease-specific survival by 43 percent, compared with hormone therapy alone. This landmark study proposes that the addition of radiation to the treatment plan should become part of the standard therapy. [Abstract]

Cardiology: Sodium Intake Increases the Risk of Sleep Apnea

Approximately 50% of all patients with heart failure (HF) suffer from sleep apnea (SA)—abnormal interruptions in breathing during sleep—increasing the likelihood of mortality. TRI’s Dr. Douglas Bradley examined the role of dietary sodium in the development of SA in HF patients. The study discovered that sodium intake was higher in patients with SA than those without. Impairment of renal function, the ability of the kidney to filter salt and remove it from the blood stream, was also found to relate to the development of SA. [Abstract]

July 1st marked the official integration of UHN and the Toronto Rehabilitation Institute. The combination will provide a wide range of translational research and services. TRI is a leading academic provider of adult rehabilitation services, complex continuing and long-term care, and is revolutionizing rehabilitation knowledge and practice through innovative research and education to maximize life.

On November 9th, UHN, in collaboration with the University of Toronto, officially launched the Techna Institute for the Advancement of Technology for Health. Techna is a new research institute designed to shorten the time interval from technological discovery to clinical application, while also stimulating the innovation cycle through clinically driven advancements and translational research. Techna is funded in part through The Princess Margaret Hospital Foundation and a generous donation from Carlo Fidani.

To find out more about Techna, please visit the institute webpage.

UHN was named as the top ranked research hospital in all of Canada. The study, conducted by Research Infosource, Canada’s leading provider of research intelligence for business and higher education, examined a total of 40 research hospitals across Canada and ranked them according to research income (all funds used to support research in the form of a grant, contribution or contract from all sources internal and external to the institution). UHN topped this list with $267,654,000 in research income for the fiscal year 2010. Collectively, the 40 Canadian research hospitals raised $2.1 billion to fund a wide variety of research programs.

This past May, Dr. Mansoor Husain was welcomed as the new TGRI Director. As a specialist in cardiovascular disease and nuclear cardiology, Dr. Husain brings outstanding clinical and research credentials to the role. As Director, he proposes to better integrate the research focus of TGRI with the medical programs of UHN by exploring new disease-focused research teams. He hopes that this will increase the capacity for patient-focused research and accelerate innovations in health care. Dr. Husain replaced Dr. Richard Weisel who served as Director for the past six years.

Health services research (HSR) is a multidisciplinary field of inquiry, both basic and applied, that examines the use, costs, quality, accessibility, delivery, organization, financing and outcomes of health care services to increase understanding of the structure, processes and effects of health services for individuals and populations. This past year, HSR was officially recognized as a research platform, joining other systematically organized areas of research. This will strengthen the vital role HSR plays in ensuring that health care remains at the forefront of innovation and continually improves, along with the health and well-being of patients.

UHN and the Princess Margaret Hospital (PMH) announced the successful renewal of the Princess Margaret Hospital Phase II Consortium (PMHC) contract through the National Institutes of Health (NIH), led by Dr. Amit Oza. In addition to being the only non-US site funded, this was the third successful N01 contract renewal for PMHC to design, develop and conduct early phase clinical trials of National Cancer Institute Cancer Therapy Evaluation Program-sponsored agents with translational emphasis in an innovative and efficient manner.

OCI/PMH, led by Dr. Pamela Ohashi, was selected as one of 27 institutions to participate in the Cancer Immunotherapy Trials Network, funded by the National Cancer Institute, to conduct phase I and II clinical trials in the area of cancer immunotherapy. Cancer immunotherapy focuses on improving the ability of the patients’ own immune systems to fight cancer. OCI/PMH is the only institution outside of the United States selected to participate in this initiative.

The Ontario Ministry of Research and Innovation awarded TWRI’s Dr. Michael Tymianski $1.4M in new funding. Financial support for the project "TRPM7 Inhibitors for the Treatment of Stroke and Myocardial Ischemia" will be used for the development of drugs targeting TRPM7, a protein implicated in cell damage, in the treatment of cellular damage arising from stroke, heart attack and retinal disorders.

Dr. Gang Zheng and colleagues were awarded new funding from the Canadian Institutes of Health Research’s Emerging Team Grant: Regenerative Medicine and Nanomedicine program to advance nanomedicine research. The team will receive $2.32M over five years to support the operation of the project.

The research project, entitled “Nanotechnology-enabled image-guided interventions in vascular and lung diseases”, will translate innovations in nanotechnology into commercially viable, clinical trial-ready products by focusing on the development of nanotechnology-enabled image-guided treatments for lung cancer and vascular diseases.

UHN signed a follow-on licensing agreement with Vexim SA, regarding a robust software algorithm for measuring the efficacy of their SpineJack® implant procedure to repair vertebral compression fractures. SpineJack® is a vertebral body implant for the stabilization of vertebral fractures. The agreement was licensed through the Technology Development and Commercialization Office at UHN.

The software and algorithm, developed by Paul Dufort in UHN’s medical imaging group, allows for the recognition and segmentation of highly deformed objects from medical scans taken in a range of contexts. The software will continue to be improved and extended, with the next phase of work aimed at incorporating MRI scans to address growing concerns about radiation exposure from CT.