Four medical scientists from Dalhousie University are the recipients of $2.6 million in funding from the Government of Canada for their groundbreaking health research.
Four clinician scientists affiliated with the Nova Scotia Health Authority (NSHA) and the IWK Health Centre also received funding, bringing the total in new health research funding to $4 million.
The funding, which is provided by the Canadian Institutes of Health Research (CIHR) project grants, will help researchers from Dalhousie and NSHA gather the kind of information they need to make real improvements to clinical practice, health service delivery, and public health policy.
The Project Grant competition is one of CIHR’s flagship funding programs. They are multi-year grants that are designed to support researchers at various stages in their careers as they conduct health research and knowledge translation projects that cover the full range of health research topics. Project grant recipients are leaders in their fields and their projects tackle pressing health issues that matter to Canadians, such as cancer, autism, heart disease, and dementia.
Highlights of successfully funded researchers
Martin Alda
Psychiatry Researcher, NSHA
Project title: Clinical and genetic factors in response to treatment of bipolar disorder
This study seeks to cut down the time it takes to find an effective treatment for bipolar disorder. Traditionally a trial-and-error approach to finding an effective treatment is used but this project seeks to better inform the process using genetic data.
Support for this project is not only local but also on an international scale. Local researchers are part of an international consortium, ConLiGen and this project has also received funding from the European group ERA PerMed Cofund.
Jason Berman
Division of Hematology/Oncology, IWK Health Centre
Project title: Using the Zebrafish as a model for chemoprevention for TP53 mutation carriers
Patients with Li Fraumeni syndrome (LFS) have a mutation in a gene called TP53 in every cell in their bodies, which puts them at much greater risk for developing cancers early in life and throughout their lifetime. While surveillance programs that include MRIs and other imaging tests have helped identify these tumours earlier so that they are more easily treated, these patients still require intensive therapy to cure their cancers. Patients who survive their first tumour are likely to have second, third and more tumours that will all need treatment. What types of cancer and when these tumours will develop is hard to predict.
The zebrafish shares similar genetics to humans, fertilizes externally producing large numbers of offspring, which are transparent and easily studied. Dr. Berman and his team have already genetically engineering zebrafish to contain the most common TP53 mutations found in LFS, and these fish develop cancers by 8-10 months of age. These fish can be screened early in development for signs that their TP53 gene is not functional and introduce additional mutations found in LFS patient tumours. The young fish can then be used to screen for drugs that restore normal TP53 and observe if cancers are prevented. By demonstrating that these responses in zebrafish are conserved in patient samples, we aim to improve the outcome for these children.
Zhenyu Cheng
Assistant Professor, Faculty of Medicine
Project title: Pseudomonas aeruginosa protease promotes chronic inflammation and immune evasion
Pseudomonas aeruginosa is a bacterial pathogen that inhabits soil and water as well as plant and animal tissues. It can be an opportunistic human pathogen, causing infections when normal immune defenses are disrupted.
Respiratory P. aeruginosa infection is the leading reason for morbidity in cystic fibrosis patients. The infections normally persist in the lungs of cystic fibrosis patients because of the formations of bacterial biofilms, and can lead to inflammation in the lung.
The goal of Dr. Cheng’s research is to characterize how a P. aeruginosa-secreted protease modulates inflammation in the context of chronic infection in CF lungs. His findings may lead to the development of new strategies for alleviating the terrible inflammation in the lungs of these patients that eventually creates the need for lung transplants.
Melanie Kelly
Professor, Faculty of Medicine
Project Title: The Serine Hydrolases: Positioned at the Axis of Endocannabinoid-Elcosanoid Signaling
The endocannabinoid system (ECS) is an important physiological regulatory system, and drugs that target this system have effects on a number of critical biological systems including synaptic transmission and immune response. The ECS is also the target for cannabinoid constituents from the cannabis plant including behaviorally active tetrahydrocannabinal (THC) that interacts with cannabinoid 1 and cannabinoid 2 receptors.
There is a tremendous interest in targeting the ECS to treat disease, particularly using indirect agonists such as enzyme inhibitors, which block the metabolism of endocannabinoids. Although there has been significant promise in pre-clinical studies, clinical trials of enzyme inhibitors have been halted due to either a lack of efficacy or toxicity.
Dr. Kelly’s research will address these important areas by:
1) providing fundamental knowledge about the manipulation of endocannabinoid signaling in the central nervous system (CNS)
2) Identifying the risks or benefits of using drugs that indirectly enhance endocannabinoid levels for therapeutic targeting of the ECS in CNS disease
Emily Gard Marshall
Associate Professor, Faculty of Medicine
Project title: The CUP Study - Comparative analysis of centralized waitlist effectiveness, policies, and innovations for Connecting Unattached Patients to primary care providers
How well do waitlists to find a family practice work and what could we do to help them work better
People who have access to a regular primary care provider (family doctor or nurse practitioner) receive better and more appropriate care and have better health outcomes than those who do not. Across Canada, 15% of people do not have a regular provider, and are referred to as “unattached patients.”
Seven Canadian provinces, including Nova Scotia, have centralized waitlists that coordinate matching unattached patients to a primary care provider. These centralized waitlists all work differently, but no one has studied how well they work.
Dr. Marshall will compare centralized waitlists in Nova Scotia, Quebec, and Ontario to see how effective they are at connecting unattached patients to primary care providers. The findings from this study will be shared with stakeholders from all the provinces.
Natalie O. Rosen
Associate Professor, Faculty of Science
Project title: A multi-method study of self-expansion in couples coping with Female Sexual Interest/Arousal Disorder
Sexual health is a fundamental aspect of quality of life; a satisfying sexual relationship is associated with better physical, psychological, and relationship health and well-being. Problems with sexual function are extremely common, especially for women. A persistent difficulty with sexual desire and/or arousal that is personally upsetting (Female Sexual Interest/Arousal Disorder or FSIAD) affects 7-23% of the general population.
Sexual desire—the key component in FSIAD—is thought to be embedded in, and influenced by, interpersonal factors, with FSIAD being coined the most ‘relational’ of sexual dysfunctions. One highly relevant interpersonal factor that has been associated with greater sexual desire and satisfaction in community couples is self-expansion. Self-expansion in relationships represents the extent to which partners facilitate the attainment of new perspectives and provide opportunities for novel and exciting experiences. For example, a couple might engage in self-expanding activities together such as learning how to cook a new type of cuisine or taking a trip to a new city to explore interesting sights.
The goal of Dr. Rosen’s study is to examine how self-expansion in relationships influences sexual desire and associated impairments in couples coping with FSIAD. The results have the potential to improve the health of couples coping with FSIAD by providing novel targets for couple interventions.
Sudeep Shivakumar
Hematology Researcher, NSHA
Project title: EPCAT III - Extended Venous Thromboembolism Prophylaxis Comparing Rivaroxaban and Aspirin to Aspirin Alone Following Total Hip and Knee Arthroplasty
The EPCAT III study is a continuation of the comparison of aspirin and blood thinners when preventing blood clots after hip and knee replacement surgery. Previous studies have shown that aspirin is just as effective and safe as a more expensive blood thinner. This results in significant cost savings to the health care system.
Blood clots are common complications following these types of surgeries and traditionally, blood thinners are given to prevent them. However, blood thinners are expensive and can lead to bleeding.
This study continues the work of the team who were previously published in the New England Journal of Medicine.
Rudolf Uher & Stan Matwin
Psychiatry Researchers, NSHA
Project title: Automated analysis of natural speech in personalized treatment for major depressive disorder
Can artificial intelligence (AI) improve on clinical intuition when treating depression? Researchers will test whether treatment selection for depression by AI (based on analyzed speech patterns) can improve upon clinical intuition during assessments and follow up visits.
Speech rhythms reflect the speaker’s mood in the moment and reflect their thought processes and motivations. Listening to speech is a key part of clinical assessment which informs treatment selection such as psychotherapy, brain stimulation or medication. Choosing which treatment will be effective is hard to predict.
Psychiatry Researcher, NSHA
Project title: Clinical and genetic factors in response to treatment of bipolar disorder
This study seeks to cut down the time it takes to find an effective treatment for bipolar disorder. Traditionally a trial-and-error approach to finding an effective treatment is used but this project seeks to better inform the process using genetic data.
Support for this project is not only local but also on an international scale. Local researchers are part of an international consortium, ConLiGen and this project has also received funding from the European group ERA PerMed Cofund.
Jason Berman
Division of Hematology/Oncology, IWK Health Centre
Project title: Using the Zebrafish as a model for chemoprevention for TP53 mutation carriers
Patients with Li Fraumeni syndrome (LFS) have a mutation in a gene called TP53 in every cell in their bodies, which puts them at much greater risk for developing cancers early in life and throughout their lifetime. While surveillance programs that include MRIs and other imaging tests have helped identify these tumours earlier so that they are more easily treated, these patients still require intensive therapy to cure their cancers. Patients who survive their first tumour are likely to have second, third and more tumours that will all need treatment. What types of cancer and when these tumours will develop is hard to predict.
The zebrafish shares similar genetics to humans, fertilizes externally producing large numbers of offspring, which are transparent and easily studied. Dr. Berman and his team have already genetically engineering zebrafish to contain the most common TP53 mutations found in LFS, and these fish develop cancers by 8-10 months of age. These fish can be screened early in development for signs that their TP53 gene is not functional and introduce additional mutations found in LFS patient tumours. The young fish can then be used to screen for drugs that restore normal TP53 and observe if cancers are prevented. By demonstrating that these responses in zebrafish are conserved in patient samples, we aim to improve the outcome for these children.
Zhenyu Cheng
Assistant Professor, Faculty of Medicine
Project title: Pseudomonas aeruginosa protease promotes chronic inflammation and immune evasion
Pseudomonas aeruginosa is a bacterial pathogen that inhabits soil and water as well as plant and animal tissues. It can be an opportunistic human pathogen, causing infections when normal immune defenses are disrupted.
Respiratory P. aeruginosa infection is the leading reason for morbidity in cystic fibrosis patients. The infections normally persist in the lungs of cystic fibrosis patients because of the formations of bacterial biofilms, and can lead to inflammation in the lung.
The goal of Dr. Cheng’s research is to characterize how a P. aeruginosa-secreted protease modulates inflammation in the context of chronic infection in CF lungs. His findings may lead to the development of new strategies for alleviating the terrible inflammation in the lungs of these patients that eventually creates the need for lung transplants.
Melanie Kelly
Professor, Faculty of Medicine
Project Title: The Serine Hydrolases: Positioned at the Axis of Endocannabinoid-Elcosanoid Signaling
The endocannabinoid system (ECS) is an important physiological regulatory system, and drugs that target this system have effects on a number of critical biological systems including synaptic transmission and immune response. The ECS is also the target for cannabinoid constituents from the cannabis plant including behaviorally active tetrahydrocannabinal (THC) that interacts with cannabinoid 1 and cannabinoid 2 receptors.
There is a tremendous interest in targeting the ECS to treat disease, particularly using indirect agonists such as enzyme inhibitors, which block the metabolism of endocannabinoids. Although there has been significant promise in pre-clinical studies, clinical trials of enzyme inhibitors have been halted due to either a lack of efficacy or toxicity.
Dr. Kelly’s research will address these important areas by:
1) providing fundamental knowledge about the manipulation of endocannabinoid signaling in the central nervous system (CNS)
2) Identifying the risks or benefits of using drugs that indirectly enhance endocannabinoid levels for therapeutic targeting of the ECS in CNS disease
Emily Gard Marshall
Associate Professor, Faculty of Medicine
Project title: The CUP Study - Comparative analysis of centralized waitlist effectiveness, policies, and innovations for Connecting Unattached Patients to primary care providers
How well do waitlists to find a family practice work and what could we do to help them work better
People who have access to a regular primary care provider (family doctor or nurse practitioner) receive better and more appropriate care and have better health outcomes than those who do not. Across Canada, 15% of people do not have a regular provider, and are referred to as “unattached patients.”
Seven Canadian provinces, including Nova Scotia, have centralized waitlists that coordinate matching unattached patients to a primary care provider. These centralized waitlists all work differently, but no one has studied how well they work.
Dr. Marshall will compare centralized waitlists in Nova Scotia, Quebec, and Ontario to see how effective they are at connecting unattached patients to primary care providers. The findings from this study will be shared with stakeholders from all the provinces.
Natalie O. Rosen
Associate Professor, Faculty of Science
Project title: A multi-method study of self-expansion in couples coping with Female Sexual Interest/Arousal Disorder
Sexual health is a fundamental aspect of quality of life; a satisfying sexual relationship is associated with better physical, psychological, and relationship health and well-being. Problems with sexual function are extremely common, especially for women. A persistent difficulty with sexual desire and/or arousal that is personally upsetting (Female Sexual Interest/Arousal Disorder or FSIAD) affects 7-23% of the general population.
Sexual desire—the key component in FSIAD—is thought to be embedded in, and influenced by, interpersonal factors, with FSIAD being coined the most ‘relational’ of sexual dysfunctions. One highly relevant interpersonal factor that has been associated with greater sexual desire and satisfaction in community couples is self-expansion. Self-expansion in relationships represents the extent to which partners facilitate the attainment of new perspectives and provide opportunities for novel and exciting experiences. For example, a couple might engage in self-expanding activities together such as learning how to cook a new type of cuisine or taking a trip to a new city to explore interesting sights.
The goal of Dr. Rosen’s study is to examine how self-expansion in relationships influences sexual desire and associated impairments in couples coping with FSIAD. The results have the potential to improve the health of couples coping with FSIAD by providing novel targets for couple interventions.
Sudeep Shivakumar
Hematology Researcher, NSHA
Project title: EPCAT III - Extended Venous Thromboembolism Prophylaxis Comparing Rivaroxaban and Aspirin to Aspirin Alone Following Total Hip and Knee Arthroplasty
The EPCAT III study is a continuation of the comparison of aspirin and blood thinners when preventing blood clots after hip and knee replacement surgery. Previous studies have shown that aspirin is just as effective and safe as a more expensive blood thinner. This results in significant cost savings to the health care system.
Blood clots are common complications following these types of surgeries and traditionally, blood thinners are given to prevent them. However, blood thinners are expensive and can lead to bleeding.
This study continues the work of the team who were previously published in the New England Journal of Medicine.
Rudolf Uher & Stan Matwin
Psychiatry Researchers, NSHA
Project title: Automated analysis of natural speech in personalized treatment for major depressive disorder
Can artificial intelligence (AI) improve on clinical intuition when treating depression? Researchers will test whether treatment selection for depression by AI (based on analyzed speech patterns) can improve upon clinical intuition during assessments and follow up visits.
Speech rhythms reflect the speaker’s mood in the moment and reflect their thought processes and motivations. Listening to speech is a key part of clinical assessment which informs treatment selection such as psychotherapy, brain stimulation or medication. Choosing which treatment will be effective is hard to predict.