Canadian awards honour top medical discoveries around the world

Toronto, ON – The Gairdner Foundation has announced the winners of the 2015 Canada Gairdner Awards, recognizing some of the most significant medical discoveries from around the world.

Among the world’s most esteemed medical research prizes, the awards distinguish Canada as a leader in science and provide a $100,000 (CDN) prize to each scientist for their work. The Canada Gairdner Awards promote a stronger culture of research and innovation across the country, inspiring the next generation of researchers.

The Canada Gairdner Wightman Award, given to a Canadian who has demonstrated outstanding leadership in medicine and medical science throughout his/her career, is awarded to:

• Dr. Janet Rossant, chief of research, the Hospital for Sick Children (SickKids), Toronto, CA

Awarded “for her outstanding scientific contributions to developmental biology and for her exceptional international leadership in stem cell biology and policy-making, and in advancing research programs for children’s illnesses.”

The work: Dr. Rossant is a world leader in developmental and stem cell biology. Dr. Rossant has provided significant insights into how an embryo develops, how genes control development and how pluripotent and other stem cells are established. Her research interests focus on understanding the genetic control of normal and abnormal development in the mouse embryo and its impact on human development and disease.

The impact: By understanding the underpinning of early development in the mouse embryo, she has contributed to the understanding of human embryo development and stem cell origins. Her interests in the early embryo led to the discovery in 1998 of a novel placental stem cell type, the trophoblast stem cell. This work has highlighted how congenital anomalies in the heart, blood vessels and placenta can arise. Further, her research on the genes controlling blood vessel development has defined novel pathways for new drug interventions in cancer. Throughout her career, Dr. Rossant has been a pioneer and innovator of new techniques to manipulate the mouse genome, enabling the mouse to become the pre-eminent model for understanding the function of the human genome sequence.

The selections for the Canada Gairdner International Awards, recognizing individuals from various fields for seminal discoveries or contributions to medical science, are:

• Dr. Lewis C. Cantley, director, Sandra and Edward Meyer Cancer Center at Weill Cornell Medical College and NewYork-Presbyterian Hospital; Margaret and Herman Sokol professor in Oncology Research; professor of cancer biology in medicine at Weill Cornell, New York, NY

Awarded “for his discovery of PI 3-Kinase, a critical component of the cell signaling machinery that plays a key role in normal functions of proliferations and growth and is de-regulated in diseases such as cancer and diabetes”

The work: Dr. Cantley’s research focuses on understanding the pathways that regulate normal cell growth and the defects that cause cell transformation leading to cancer. Along with colleagues he discovered a growth signaling molecule called phosphoinositide 3-kinase (PI3K), a key factor in tumor growth. His discovery showcased a new language of how cells control themselves internally.

The impact: He has worked to identify new treatments for cancers that result from defects in the pathway. His discovery has resulted in various treatments for personalized cancer therapy and diabetes.

• Dr. Michael N. Hall, professor, Biozentrum, University of Basel, Basel, Switzerland

Awarded “for his discovery of the nutrient activated protein kinase TOR and elucidation of its central control of cell growth, critical to development and aging and widely implicated in cancers, diabetes, cardiovascular and immune diseases.”

The work: Cell division, growth and death are the most fundamental features of life. Dr. Hall discovered and named the protein “target of rapamycin” (TOR), which regulates cell growth. In TOR, Hall found a key protein in cellular communication that when blocked pharmacologically can contain the uncontrolled cell growth and division that is typical for cancer. TOR is also a central controller of cell growth that plays a key role in development and ageing. TOR was the first protein that demonstrated to influence longevity in all of the four species that scientists commonly use to study ageing: yeast, worms, flies and mice.

The impact: Dr. Hall’s discovery has contributed to a deeper understanding of fundamental life processes such as cell division, growth and death. Insights into TOR signaling pathways and their involvement in disease have opened the door for new therapeutic strategies for cancer, obesity, diabetes, and cardiovascular disease. Pharmacological inhibition of TOR also helps patients accept transplanted organs.

• Dr. Lynne E. Maquat, director of the Center for RNA Biology: From Genome to Therapeutics, and professor of biochemistry and biophysics at the University of Rochester School of Medicine and Dentistry; J. Lowell Orbison Endowed Chair

Awarded “for the discovery of the mechanism that destroys mutant messenger RNAs in human cells, nonsense-mediated mRNA decay, which is critically important in both normal and disease states.”

The work: Messenger RNA (mRNA) takes genetic instructions from DNA and uses them to create proteins that carry out multiple cellular functions. Dr. Maquat discovered nonsense-mediated mRNA decay (NMD) in human cells. NMD is a quality control mechanism that removes flawed messenger RNA molecules that, if left intact, would lead to the production of abnormal proteins that could be toxic to cells and initiate disease. Cells also use this pathway to better respond to changing environmental conditions. For example, breast cancer cells inhibit this pathway to augment their response to chemotherapy and hasten cell death.

The impact: Nonsense-mediated mRNA decay functions in one-third of inherited disorders, such as cystic fibrosis, and one-third of acquired diseases, including many forms of cancer. Her work has furthered our understanding of the molecular basis of human disease and provides valuable information to help physicians implement “personalized” or “precision” medicine by treating the disease mutation that is specific to each individual patient.

• Dr. Yoshinori Ohsumi, honorary professor, Frontier Research Center, Tokyo Institute of Technology (Tokyo Tech), Tokyo, Japan

Awarded “for pioneering the molecular elucidation of autophagy, an essential intracellular, degradation system and when disordered, is linked to many diseases including neurodegeneration, cancer, and infection.”

The work: He was the first person to visually observe the function of autophagy (self-eating), whereby cells clean up the garbage within them by killing invaders and keeping healthy cells. It works as a cell recycling system to maintain homeostasis within the body. He then clarified the mechanism of autophagy and the genes involved.

The impact: Autophagy is now regarded as a vital cell-recycling system and may aid in future developments to treat neurodegenerative diseases such as Alzheimer’s, cancer and other age-related diseases. Dr. Ohsumi’s research findings have since been applied to autophagy in animals as well, and many researchers are now working to further clarify the molecular mechanism and physiological significance of this process.

• Dr. Shimon Sakaguchi, distinguished professor, vice director, Laboratory of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan

Awarded “for his discovery of regulatory T cells, characterization of their role in immunity and application to the treatment of autoimmune diseases and cancer.”

The work: To stay healthy our immune system needs to discriminate
between itself and invaders (non-self). When unable to differentiate between the two, the immune system destroys healthy cells or tissues causing autoimmune diseases. Dr. Sakaguchi discovered regulatory T (Treg) cells which help maintain order in the immune system and act as a ‘self-check’ to prevent excessive reactions as without Treg cells the body would attack the healthy cells and die. He was the first to determine their molecular basis and function.

The impact: Within his laboratory, Dr. Sakaguchi demonstrated that increasing the number of Treg cells can prevent and treat autoimmune diseases. Further, Treg cells suppress the immune system against cancer and there are now several clinical trials within this area.

The Canada Gairdner Global Health Award, recognizing someone who is responsible for a scientific advancement that has made a significant impact on health in the developing world, goes to:

• Dr. Peter Piot, director of the London School of Hygiene & Tropical Medicine; professor of Global Health, London, U.K

Awarded “for his co-discovery of the Ebola virus, his many contributions to HIV/AIDS research and his extraordinary leadership in the global response to the HIV/AIDS epidemic, especially in Africa.”

The work: Dr. Piot is a co-discoverer of the Ebola virus and its modes of transmission and its epidemiology. His pioneering work on HIV/AIDS in Africa revealed a major heterosexual HIV epidemic, established much of the knowledge of the clinical manifestations, natural history and epidemiology of HIV in Africa, including the first studies showing the effectiveness of HIV prevention in high risk populations. He also identified several original risk determinants for HIV transmission. His team was the first to document the association between tuberculosis (TB) and HIV in Africa, and the wide genetic diversity of HIV-1 in Africa, as well as a related immunodeficiency virus in chimpanzees.

The impact: Dr. Piot played a leading role in bringing the AIDS epidemic to the forefront of global attention, raising international commitments to its funding and building scientifically grounded responses to its control and treatment. His team’s work on the strong association of tuberculosis and HIV in Africa, followed by clinical and therapeutic studies, led to new guidelines for managing tuberculosis in Africa. His studies on the prevention of HIV infection among high risk populations were again among the first in Africa, and demonstrated that such prevention is possible.

The Canada Gairdner Awards will be presented at a dinner in Toronto on October 29^th, 2015 as part of the Gairdner National and Student Outreach Programs, a two week lecture series given by Canada Gairdner Award winners at more than 22 universities from St John’s to Vancouver. The national program reaches students across the country, making the superstars of science accessible and inspiring the next generation of researchers.

“The Canada Gairdner Awards distinguish Canada as a leader in biomedical research, raising the profile of science both nationally and on the world stage,” said Dr. John Dirks, president and scientific director, Gairdner Foundation. “This year’s winners are an exceptional example of the wide implications basic cellular discovery can have on future translational discoveries.”