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2007 Capital Equipment Grants

Dr. Jim Fawcett, Dept. of Pharmacology

$21,780  -  explores mechanisms of brain repair and cancer cell development
Restoring lost motor function after spinal cord injury and the development of cancer may not seem to have a lot in common. Yet these vastly different aims are linked by common threads – protein-based cell signalling events – which Dr. Jim Fawcett is determined to unravel.

A Tier II Canada Research Chair in Brain Repair, Dr. Fawcett joined Dalhousie Medical School’s spinal cord research group in 2006. He is working with Dr. Vic Rafuse and Dr. Rob Brownstone to learn how the spinal cord is wired – and find ways to regenerate and re-wire neurons required for movement and walking after they’ve been injured by trauma or disease.

A process known as ‘axon guidance’ is one of the keys. “In the developing nervous system, each neuron sends out an axon, a long tendril that grows out from the neuron,” Dr. Fawcett explains. “The axon senses the outside world and homes in on protein signals that guide it to the location that will make the right brain-body connection.” Controlling axon guidance is crucial to restoring lost function after spinal cord injury.

Dr. Fawcett has discovered a signalling molecule that plays a critical role in developing the spinal circuits needed for walking. He has also identified signalling proteins involved in deciding a cell’s fate – including the decision of normal cells to develop into cancerous cells. “We study simple protein-protein interactions to understand what compels axons to migrate and certain cells to become cancerous,” he says. “Because there are proteins involved, we have something to work with – to enhance spinal cord repair and interfere with cancer development.”

An assistant professor in the Department of Pharmacology and the Division of Neurosurgery, Dr. Fawcett received equipment support and a New Investigator Award from the Dalhousie Medical Research Foundation in 2007. The Brain Repair Centre and Dalhousie Faculty of Medicine’s collegial environment were among the features that attracted him to Halifax. “I could tell that something big is happening here,” he says.

Dr. Jan Rainey, Biochemistry & Microbiology

$20,800  -  explores atomic mechanisms of heart muscle destruction
Dr. Jan Rainey is taking the closest possible look at how heart muscle is destroyed after a heart attack. He’s studying post-heart-attack damage at the smallest unit of matter – the atom.

“Complex as humans are, we are composed of atoms of elements such as carbon, nitrogen, hydrogen, sulfur, phosphorus and oxygen, along with some minerals like calcium, sodium and potassium,” notes Dr. Rainey. “But there are tens of thousands of atoms in a single molecule of protein.”

Dr. Rainey is exploring the atomic structure of a protein known to trigger cell damage immediately following a heart attack. “After a heart attack, a protein called the ‘sodium-hydrogen exchanger’ becomes more active and draws in more sodium than usual,” he explains. “This sets off a cascade of changes and events that contribute to subsequent damage.”

Charting the atomic structure of this protein will reveal the shapes of its sodium and hydrogen receptors – so a drug can be designed to bind with a receptor to disrupt the protein’s activity and halt the ongoing destruction. “It may be possible to protect the heart from this post-heart-attack damage,” he says. “This would preserve heart function and provide a much better chance of recovery.”

Dr. Rainey is also investigating the role of the sodium-hydrogen exchanger protein in diabetes.  This protein functions at a slower rate in people with diabetes. Since it functions in every cell in the body, it may contribute to the many health complications experienced by diabetics.

Dalhousie Medical Research Foundation has provided Dr. Rainey with capital equipment funding to set up his lab. He joined Dalhousie as an Assistant Professor in the Department of Biochemistry & Molecular Biology in November 2006, following postdoctoral training in world-renowned structural biology laboratory at the University of Alberta.

Graham Dellaire, Pathology

$26,276  -  maps nuclear neighbourhoods and their role in cancer
The nucleus contains critical genetic information, but as Dr. Graham Dellaire explains, it is not simply a ‘bag of DNA.’ “The nucleus turns out to be highly compartmentalized. Different regions have different functions, and so do the pathways and structures that connect these ‘nuclear neighbourhoods,’” he says. “Structures known as PML nuclear bodies play a major role in such cancer-related processes as DNA repair, cell death and tumour suppression.”

Among his many pursuits as Dalhousie Medical School’s first ‘Cameron Research Scientist,’ Dr. Dellaire is studying how PML nuclear bodies in living cancer cells respond to chemotherapy and radiation. “Their response will tell us if treatment is working, within 24 hours… instead of weeks,” he says. “Through use of such biomarkers, a patient’s treatment could be quickly adjusted to improve survival and avoid the unnecessary suffering and expense of ineffective treatments.”

Many of Dr. Dellaire’s experiments rely on the new gamma irradiator, purchased with the proceeds of the 2005 Molly Appeal for Cancer Research. “It’s a key facility for me,” he says. “It’s the most effective and clinically relevant way to damage DNA for the study of cancer development.” He also brings expertise to Dalhousie in the emerging field of ‘correlative light and electron microscopy’, which allows scientists to study nuclear structures, including DNA and PML bodies, at unparalleled detail within the cell.

Dr. Dellaire joined Dalhousie’s Department of Pathology in early 2007, from The Hospital for Sick Children in Toronto. In addition to the Cameron Research Scientist award, funded through the Dr. Owen and Mrs. Pearle Cameron Endowment for Cancer Research, he holds a prestigious CIHR Senior Postdoctoral Fellowship award. He has also applied for three patents for methods he has developed to study nuclear structure and function, and biomarkers for cancer.

Dr. Jun Wang, Pediatrics / Microbiology & Immunology

$24,681  -  pioneers needle-free Chlamydia vaccine
Not only is Dr. Jun Wang developing the first-ever vaccine against Chlamydia, she is designing it in the form of a nasal spray. “Taking the vaccine through the nose generates immunity in areas of the body where mucous is found,” she explains. “These are the areas that the bacteria attack, so specific immunity in those areas gives the strongest protection.”

There are several strains of the Chlamydia bacteria. “In Western nations, we are most familiar with Chlamydia as a sexually transmitted disease that infects the genital tract,” notes Dr. Wang. “There are other strains, however, that infect the eyes and lungs.” All forms of Chlamydia can go undetected, and untreated, for long periods of time.

“Chlamydia is insidious… there may be no symptoms, but serious damage is taking place,” Dr. Wang says. Genital Chlamydia can lead to pelvic inflammatory disease and infertility. It increases the risk of contracting of HIV and human papillomavirus (HPV) – a known cause of cervical cancer. Chlamydial eye infections, a major public health problem in developing nations, can lead to blindness. The airborne strain can lead to ‘Chlamydia pneumonia,’ chronic bronchitis and chronic obstructive pulmonary disorder (COPD) – and even atherosclerosis and multiple sclerosis.

Dr. Wang is conducting ‘proof-of-principle’ studies in the Canadian Centre for Vaccinology at the IWK Health Centre, with equipment support from the Dalhousie Medical Research Foundation. “I have planted genes from three strains of Chlamydia into a modified cold virus to create a nasal vaccine formula,” she says. “If it proves to generate long-term immunity in vulnerable mucosal sites, I can take it to the next step.”

In Canada, Dr. Wang expects the vaccine would be targeted to young people, before they become sexually active. “Needle-free delivery offers many advantages,” she says. “It provides targeted immunity, it’s less expensive and, of particular importance in developing nations, giving the vaccine doesn’t require highly trained health professionals or sterilized needles.”

 

Dr. Chris Richardson, Microbiology & Immunology

$20,000  -  fights viruses and cancer in Canadian Centre for Vaccinology
Dr. Chris Richardson is fighting the deadly effects of bloodborne hepatitis viruses on two fronts. A virologist and cancer researcher in one, Dr. Richardson is investigating how the “X protein” of the hepatitis B virus causes liver cancer. He holds a Terry Fox Grant from the National Cancer Institute of Canada for this work.

“Liver cancer is the third-leading cause of cancer deaths in the world; 53 per cent of liver cancers are caused by hepatitis B,” says Dr. Richardson. “There is a vaccine against hepatitis B, but two billion people are already infected worldwide. About 500 million of these people will develop liver disease – most likely cirrhosis or cancer – over the next 20 to 30 years.” Another 25 per cent of liver cancers are triggered by hepatitis C virus. Dr. Richardson is also studying how the liver’s immune response to this virus leads to cancer.

An international expert on measles virus, Dr. Richardson is engineering this common virus into a multi-purpose vaccine – against measles and a host of lethal agents including hepatitis C, HIV, SARS, avian flu, and West Nile viruses. “I’m working with the same virus that’s been used to vaccinate against measles for decades,” he says. “It’s a safe vehicle for delivering fragments of the more virulent viruses to the immune system.”

Remarkably, the vaccine strain of the measles virus is also a potential cancer treatment. Dr. Richardson has discovered receptors for the measles virus on tumour cells. “This virus seeks out and grows well in many tumours,” he notes. He is working in his lab and in cooperation with the Mayo Clinic on further measles-versus-cancer studies. He works with Harvard Medical School and the Massachusetts Institute of Technology on various other projects.

Dr. Richardson is a Professor in the departments of Microbiology & Immunology and Pediatrics and a Tier I Canada Research Chair in Vaccinology and Viral Therapeutics. Prior to joining Dalhousie Medical School and the Canadian Centre for Vaccinology (Halifax) in 2006, he held senior appointments at the University of Toronto and Ontario Cancer Institute for 12 years, following a decade at McGill University and the National Research Council.

Craig McCormick, Microbiology & Immunology

$30,000  -  studies how a virus triggers Kaposi’s sarcoma
Scientists are finding more links between viruses and cancer every day. “Right now, we know that about 15 per cent of all cancers are caused by viruses,” says Dr. Craig McCormick, a cancer researcher at Dalhousie Medical School. “These include human papilloma virus, which leads to cervical cancer, and the hepatitis B and hepatitis C viruses, which can cause liver cancer.”

Dr. McCormick is studying how a recently discovered herpes virus – human herpesvirus-8 – triggers Kaposi’s sarcoma, a form of skin cancer. Although Kaposi’s sarcoma can usually be cured, it is deadly when it strikes people with weakened immune systems – such as those who are battling AIDS. The cancer is taking a terrible toll in Africa, where it was common even before the AIDS epidemic.

In addition to studying how Kaposi’s sarcoma develops in AIDS, Dr. McCormick is looking at the changes that take place when a cell is infected with human herpesvirus-8. “I’m trying to pinpoint the event that starts the cancer process and trace the subsequent molecular steps as cancer develops,” he explains. “This knowledge will help us understand the origins of cancer, and may ultimately lead to effective new therapies.”

Dr. McCormick joined Dalhousie’s Department of Microbiology & Immunology in 2006, after completing postdoctoral training at the University of California, San Francisco. The Dalhousie Medical Research Foundation provided crucial start-up funding to help him renovate and equip his lab – through the Dalhousie Cancer Research Program and the exceptionally generous contribution of $56,000 from a DMRF donor, Margot Spafford of Halifax.

“The community here has been incredibly welcoming and supportive,” he says. “I’m very pleased to be part of Dalhousie’s growing cancer research community.”


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