Net Results Express Title
February 2004

Inside this issue...

The Continuum of Research at UHN

The Overview

Basic research

Translational research

Clinical research
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UHN's Research Internet Site
From Basic to Clinical:
the Continuum of Research at UHN
 A special issue
    UHN researchers

    The continuum of research—our ability to pursue fundamental research questions, devise treatments based on our observations and then test these treatments in patient volunteers—is a particular strength of UHN. Several factors contribute to this strength:

    • Being part of a patient care environment leads to the development of clinically-relevant research questions: e.g., Why is chemotherapy not working in this case? How can we help treat this side effect?
    • The proximity of basic researchers and clinician-scientists provides the full spectrum of expertise required to tackle human health problems
    • Finally, as a hospital-based research institute, UHN provides a safe and regulated environment for conducting research with human samples and human volunteers—an advantage not available to researchers in universities and private sector R&D departments

    “The interplay between research labs and patient care is a driver of innovation” says Dr. Christopher Paige, Vice President, Research. “You can think of this continuum as a 'time-to-patient-impact' chain. UHN researchers make important contributions along the entire length of the chain.”
    Biomedical Research Types: The Overview
      Research Schematic
    Basic research:
    • Primarily conducted to understand normal and abnormal processes
    • May appear to be only indirectly related to a specific disease, but the same basic research finding is often relevant to many diseases
    • Many biological processes are conserved across species. e.g., the genes that control the cell cycle in yeast are the same as those that control the cell cycle in humans, so basic research into these processes can make use of animal and in vitro models
      Cancer Genes Keep Genome in Check
        Before scientists can develop a cure for a disease they must first understand how cells divide and how they die, and the answer to this lies in our genes. UHN researchers Drs. Angela Cheung (TGRI/TGH), Ming-Sound Tsao, Jeremy Squire, Robert Bristow (OCI/PMH), Razq Hakem, and Tak Mak (AMDI/OCI/PMH) recently made progress on this front with their finding that the breast cancer susceptibility gene BRCA2 has an important role in repairing DNA damage in immune cells. They have shown that when this gene is mutated in mice, genetic material becomes unstable and prone to errors. When this mutation is coupled with a mutation in another cancer gene, p53, cell growth goes awry and tumours develop. Together, these findings constitute new insight into the mechanisms of cancer development.
        Cancer Res 2002 Nov 1; 62(21):6194-204
        Originally published in Net Results EXPRESS (January, 2003)
      Protein is Key for Zapping Infected Cells
        The first explanation for why people with Wiscott-Aldrich syndrome (WAS) suffer from recurrent infections was recently reported by Dr. Kathy Siminovitch (TGRI/TGH). WAS, a disorder that affects four out of every 1M male children, is caused by a mutation in the WAS gene. Dr. Siminovitch’s research shows that immune T cells require the WAS protein to successfully eradicate infected cells from the body—a process that goes awry in patients with this disease.
        Immunity. 2003 Jan;18(1):141-54
        Originally published in Research Report 2003.
    Translational research:
    • Validates if new knowledge obtained in basic research applies to human health and disease
    • Conducted to better understand specific aspects of human health
    • The first step in developing new or improved diagnostic tests, therapies or procedures
    • Can include small-scale clinical research
    Examples of Translational Research

      Using Forces of Nature to Engineer Better Treatments
        Research by Drs. Ren-Ke Li, Richard Weisel and Donald Mickle (TGRI/TGH) shows that a mechanical stretch regimen can enhance the formation and strength of cell-engineered cardiac tissue. Growing heart cells on a 3-D biodegradable framework, the team used a computerized stretch machine to apply controlled forces to the cell seeded graft. The regimen improved the growth and organization of the cells, producing tissue grafts that were stronger than grafts engineered without the stretch regimen. This research will help build better cardiac grafts for the repair of heart defects, and may improve the long-term results of cardiac surgery.
        Circulation. 2002 Sep 24;106(12 Suppl 1):I137-42
        Originally published in Research Report 2003.
      Scientists One Step Closer to Personalizing Cancer Care

        chemotherapy Personalized cancer therapy has the goal of understanding the specific genetic mutations that produce an individual tumour and how that tumour will respond to treatment. A better understanding of this is the first step towards developing improved screening procedures and therapies for cancer patients. Recently, Drs. Malcolm Moore and Steve Gallinger (OCI/PMH) and Christine Ribic brought personalized cancer therapy for colon cancer patients one step closer to reality with the development of a simple genetic test designed to determine if chemotherapy will be an effective treatment for their cancer. Their research shows that 100% of patients who have a specific type of mutation in their tumour called “high-frequency microsatellite instability” do not benefit from chemotherapy.
        N Engl J Med. 2003 Jul 17;349(3):247-57
        Originally published in Net Results EXPRESS (Summer, 2003)
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