Investigating sex differences in dyspnea across the spectrum of chronic obstructive pulmonary disease severity

Chronic obstructive pulmonary disease (COPD) results in breathlessness, reduced activity level and quality of life. The number of women with COPD in BC is increasing. Healthy women experience more breathlessness during exercise compared to men. Women with mild COPD experience even more breathlessness and report worse quality of life. The basis for sex differences in breathlessness across the full spectrum of COPD disease severity has not been studied and is the main focus of our proposed research.

We will explore how breathlessness differs between women and men with mild-to-severe COPD in a group of patients that undergo lung function testing and specialized exercise testing as well as using data from a Canadian cohort study of COPD patients. We will also use high resolution imaging of the lungs to relate structural changes due to COPD to the symptoms women experience.

This is the first study to explore sex differences in breathlessness across COPD disease severity from two perspectives, using detailed exercise tests and a complementary COPD database. Understanding breathlessness in women with COPD is a first step in order to develop effective treatment strategies for the increased symptoms women experience.

Redefining atherosclerosis: Characterizing and targeting smooth muscle cell foam cells for the treatment and prevention of coronary heart disease and stroke

Heart attack, heart failure, and stroke are major causes of disability and death in BC and worldwide. The main cause of these conditions is the buildup of blockages or "plaque" in arteries in a process called atherosclerosis. For a long time, it was thought that the main place where fats (like cholesterol) build up in plaque are white blood cells called macrophages, but our laboratory made the novel discovery that it is actually smooth muscle cells (SMCs) in arteries that are most prone to becoming cholesterol-overloaded, which has important implications on developing ways to prevent heart attack and stroke.

We now propose to perform an in-depth characterization of SMCs to understand how they become overloaded with cholesterol. In addition, we will determine whether differences in SMC gene expression protect some people from plaque formation, how cholesterol-overloaded SMCs in human hearts respond to cholesterol-lowering medications, and whether turning on a particular gene in SMCs can prevent them from forming plaque and remove excess cholesterol from SMCs after it has been deposited. This work will provide vital new knowledge to reduce the burden of heart attack, stroke and heart failure in BC and beyond.

Quantitative Isotype Profiling And Dynamics Of SARS-CoV-2 Infections: Next-Generation Serology

We are making a blood test that will tell us a lot of information about the body’s response to the COVID-19, including whether a person is likely to get really sick or will easily fight off the virus. The blood test is will be easy to take, using only a drop of blood from the tip of the finger. The test is run using cutting-edge technology so that we can test a lot of people, at low cost, while getting the right results. The test will help prevent people from getting severely sick from COVID-19 by letting doctors know BEFORE things get worse that their patient may need additional care to help fight off the virus. For our citizens most at risk, like the elderly and those with other medical conditions, the results can be used to direct resources and support where they are needed most.

Quantitative Isotype Profiling and Dynamics of SARS-CoV-2 Infections: Next-Generation Serology

We are making a blood test that will tell us a lot of information about the body’s response to the COVID-19, including whether a person is likely to get really sick or will easily fight off the virus. The blood test is will be easy to take, using only a drop of blood from the tip of the finger. The test is run using cutting-edge technology so that we can test a lot of people, at low cost, while getting the right results. The test will help prevent people from getting severely sick from COVID-19 by letting doctors know BEFORE things get worse that their patient may need additional care to help fight off the virus. For our citizens most at risk, like the elderly and those with other medical conditions, the results can be used to direct resources and support where they are needed most.

The effects of 60% oxygen during exercise training in patients with fibrotic interstitial lung disease

Breathing discomfort is common in patients with interstitial lung disease (ILD) and often results in an inability to perform physical activity, leading to a poor quality of life. Exercise training can reduce breathing discomfort and enable ILD patients to perform physical activity. However, severe breathing discomfort makes it challenging for these patients to withstand the amount of training they need to get the most benefit. A recent study showed that ILD patients breathing supplemental oxygen had less breathing discomfort and were able to exercise for longer compared to breathing room air. Another study showed that breathing supplemental oxygen was safe for patients with ILD for a single exercise session. However, we still do not know if these findings can be applied to a long-term exercise program.

Therefore, the purpose of this study is to determine if using a higher amount of oxygen during a rehabilitation program is a safe intervention that translates to greater benefits from training compared to the same regimen without the additional oxygen. We are also interested in examining if higher intensity training sessions with added oxygen affects every day physical activity levels.

Assessing Small Airway Disease Heterogeneity in Asthma to Identify Novel Therapeutic Targets

Asthma is a serious public health issue in Canada and in the world, affecting more than 300 million people globally. To date, clinical trials have established that current treatment strategies for asthma can relieve patient symptoms, but none are able to reverse the disease process. It is known that in asthmatic lungs, the airways -tubes that allow air to flow in and out of the lungs for breathing – are continually injured and scarred in a process called fibrosis. The smallest airways in the asthmatic lung are the main sites of fibrosis and thought to have the greatest contribution to disease symptoms; however, current methods used to assess asthma are unable to provide information on the smallest airways.

Assessing these smaller airways could provide new ways to develop drugs to resolve the scarring that occurs in asthma. In this project, we will use new, more powerful imaging methods to determine the contribution of the small airways scarring in asthma and to identify the genes involved in this process. We will then develop laboratory models of the disease using patient lung cells that may be used in the future to develop new drugs to target the genes involved and resolve the scarring and blockade in the airways of asthmatic patients. The potential new drugs that will be found in this research will help to relieve the burden of asthma in BC.

 

HEARTBiT: A novel multi-marker blood test for management of acute cardiac allograft rejection

Patients receive heart transplants as a life-saving measure after heart failure; thus, ensuring the success of the transplant is of utmost importance. Rejection is a primary cause for heart transplant failure, and consequently, heart transplants are monitored at least 12 to 15 times within the first year of operation. However, current monitoring requires biopsies, a surgical procedure which requires repeated sampling of the heart muscle. This procedure is invasive, expensive, and stressful to patients. Replacing the biopsy with a simple blood test can greatly improve patient quality of care and reduce healthcare costs.

Therefore, my goal is to develop a new blood test to monitor rejection following heart transplants. Using sophisticated computer algorithms, our group discovered molecules in the blood that can discriminate between patients who have rejected their heart transplants and those who have not. My goal is to develop a blood test to precisely measure these molecules. Also, I will study these molecules for their biological role in heart rejection process by examining immune cells and damaged heart cells found in biopsies. Accomplishing these research goals will produce a valuable clinical tool that can diagnose rejection in a fast, accurate, cost-effective, and minimally invasive manner.

Improving sepsis outcomes with anti-PCSK9 monoclonal antibody therapy

Sepsis is a severe disorder that occurs when human defense cells fight off an infection in an uncontrolled manner that can cause organ damage and death. Unfortunately, there is no specific treatment for sepsis, and there is a limited understanding of the mechanisms driving this deadly disorder.

During infection, toxins are released in the blood and carried inside cholesterol particles, which are removed from the blood by the liver. People with decreased levels of PCSK9 (proprotein convertase subtilisin/kexin type 9), a protein that normally regulates cholesterol particle levels, seem to have an increased ability to clear toxins from their blood. This project aims to test if inhibiting PCSK9 increases the removal of toxins from blood during sepsis and reduces organ damage and mortality. The findings of this research can lead to improved understanding and management of sepsis, and potentially a new treatment for sepsis that could save thousands of lives every year in the future.

Targeting the complement system in Alzheimer’s disease

Many seniors aged 65 or older experience “age-associated memory impairment,” a normal aging process. However, Alzheimer’s disease is different, and not a normal part of aging. Alzheimer’s is a progressive brain disease with gradual loss of nerve cells and resulting problems with thinking, memory, and movement. Changes in the brain can start to happen 20 years before any memory problems appear.

Currently, no treatments are available to cure Alzheimer’s disease; however, if the disease is diagnosed and treated at an early stage, patients have a greatly improved quality of life.

Measurement of some proteins in a body fluid found in the brain and spinal cord has been used to aid in diagnosis. The sample collection is performed by inserting a needle into the spinal canal. People are usually reluctant to take the test, which causes a delay in diagnosis.

Dr. Shi’s research aims to develop a new test that could help doctors diagnose Alzheimer’s disease at an early stage. This new test is different from the current tests in two ways in that it uses blood instead of spinal fluid, which is much easier to get through venipuncture; and uses a new technique that is more sensitive and specific.

The resulting blood test could be a convenient and accurate way of diagnosing Alzheimer’s disease at an early stage.

Structural valve degeneration in bioprosthetic heart valves

Bioprosthetic heart valves (BPHVs), valves made of biologic tissues rather than synthetic materials, have revolutionized the treatment of heart valve disease, which constitutes a significant health and economic burden in BC, Canada and around the world. BPHVs serve as an alternative to mechanical valves, which require lifelong treatment to prevent clotting and therefore lead to an increased risk of bleeding.

With the development of new transcatheter methods for delivery of BPHVs, they now represent the overwhelming majority of valves. Despite these successes, the long-term durability of BPHVs is not well established and remains a concerning potential limitation.

Dr. Sellers’ research will look to determine how BPHVs degenerate and potential strategies to assess this in patients. This will include using a combination of analysis of dysfunctional valves and novel imaging approaches using computed tomography (CT) imaging.

The results of this research will help determine the long-term durability of BPHVs and improve decision-making for patients with heart valve disease.