Mosquitoes are the deadliest animals on the planet. Many species use sophisticated sensory systems, including smell and taste, to locate human beings and other animal hosts in their environment as a source of blood. When they blood-feed, they can transmit microorganisms that cause human diseases including malaria and dengue fever. After converting a blood-meal into eggs, a female mosquito must find an appropriate body of water to lay eggs where her offspring will thrive. Selecting an egg-laying site is an important part of the mosquito lifecycle, since the juvenile larval and pupal stages are aquatic and cannot move from where they hatch. Mosquitoes do not fly far, and so their choice of breeding site strongly influences where they can be found as adults and thus, where they can transmit disease.
The goal of my research is to understand how mosquitoes use their sense of smell and taste to make decisions about who to bite and where to lay eggs. I use techniques to modify their DNA and to look at the activity in their brains under a microscope. Ultimately, this research will help us understand why some mosquitoes are more deadly than others and provide the basis for mosquito control strategies such as traps and repellents.
There are growing differences in health among population groups due to unfair social conditions that disadvantage some people more than others in British Columbia and beyond. Health systems play a role in holding this problem in place by presenting unnecessary barriers to accessing quality healthcare. Health systems also have a key role in closing these gaps by taking action to change the underlying conditions that shape health and wellbeing. The Population Health Approaches to Implementing Research (k)Nowledge for Equitable Systems & Strategies (PHAIRNESS) Research Program aims to make visible and intervene on systems-level problems in three connected systems: health systems, surveillance systems and research systems. By working closely with health systems, communities and people who are impacted by these issues, research findings will be relevant, useful, and ready to be rapidly applied to improve health systems and support the wellbeing of all people in British Columbia.
Plants are endowed with biological catalysts (enzymes) that make natural drugs used to treat various human illnesses. Among these, the Chinese happy tree (Camptotheca acuminata) produces the anticancer drug camptothecin. Although camptothecin is readily convertible to the more potent drugs topotecan (Hycamtin) and irinotecan (Camptosar), this requires chemical synthesis steps which rely on toxic chemicals and petroleum-based resources.
Our research program aims at developing multidisciplinary approaches to discover and modify happy tree’s enzymes that facilitate the production topotecan, irinotecan and new camptothecin-derived analogues. We aim to rapidly generate 25-50 camptothecin-derived analogues by biotechnological means and test these compounds using in vitro and cellular assays to assess potential anti-cancer activity.
Our biosynthetic approach will allow us to explore the untapped medicinal potentials of a whole host of novel camptothecin-related chemicals in addition to topotecan and irinotecan. Long-term efforts, also ongoing in our laboratory, will focus on synthetic biology approaches to scale up production of compounds that show promising bioactivity.
Morphogenesis is the process by which an organism develops its shape. Defects in this process are linked to several diseases and defects such as cancers, heart defects at birth, and cleft lip/palate. The study of morphogenesis is critical to understanding these conditions and identifying new treatments.
Cytokinesis, a critical step of cell division that separates a dividing cell into two daughter cells, plays a major role in morphogenesis. It not only contributes to the multiplication of cells but also their arrangement within their space, giving rise to different structures. It does this by controlling the position and orientation of division—a process called symmetry-breaking. The coordinated flow of a gel layer on the cell surface—cortical flow—is a driving force of symmetry-breaking.
The goal of this research is to understand the mechanisms that control cortical flow during morphogenesis. Using genetic methods and advanced microscopy in living cells, we have found new molecular pathways that control the speed and direction of cortical flow.
By shedding further light on these mechanisms our research will identify molecules and pathways which can be used to develop new medicines to prevent and cure morphogenesis defects.
Fear memory, like that occurring in post-traumatic stress disorder, imposes pronounced health and financial burdens. Our laboratory seeks to understand and therapeutically disrupt the neurobiological elements of fear memory.
To do this, we take a multidisciplinary approach that combines cutting-edge experimental and computational techniques. To begin, in mice that have obtained fear memory in a laboratory setting, we measure the expression of every gene in the mouse genome for thousands of individual brain neurons. From these Big Data, we identify genes and neuron types that participate in fear memory. Using genetic and pharmacologic approaches, we manipulate these genes and neuron types with the aim of disrupting fear memory in a safe, acute, and precise way.
The results of this research will provide a comprehensive understanding of the basic biology of memory, help to innovate novel targets and approaches for disrupting fear memory, and generate a framework with which other anxiety and memory disorders may be interpreted. In the long term, we aim for these results to guide the generation of new therapeutic approaches for preventing traumatic fear memory in humans.
Cancer is a disease of the genome that disrupt the cells’ key functions and make them grow uncontrollably. DNA sequencing projects have led us to discover that cancer cells involve many genetic changes and that even in a single tumour, there are often multiple cancer cell populations that each carry their own mutations.
Understanding this collection of mutations is important because we need to select therapies that kill all of the cancer cells, not just some of them. Unfortunately, existing computer programs for analyzing “normal” human genome data generated by genome sequencing technologies are limited in scope because they cannot fully characterize all the mutations present in the individual cells of a tumour tissue.
Ideally, researchers would like to monitor how the genomes of cancer cells mutate over time, and how cancer cells travel through the blood stream or the urinary tract and colonize other tissues, forming metastatic tumours. The new liquid biopsy technology has made it possible to capture tumour DNA circulating in the blood stream and to sequence it, however analyzing such data and identifying the spectrum of mutations in an individual patient will require new mathematical and computational approaches.
Brain disorders are among the most significant health problems of modern day with enormous medical, social and economic burdens in British Columbia, Canada and globally. There is a substantial gap between the burden of brain disorders and the resources available to treat them. Neurodevelopmental disorders are particularly devastating, placing a heavy emotional and economic burden on children and their families. A major challenge in tackling these disorders is the inability to obtain and study brain cells directly. New technologies which allow stem cells to be transformed into brain cells are starting to help overcome this hurdle.
By studying brain cells derived from human stem cells, Dr. Pouladi aims to
- understand how brain disorders develop and
- to identify new ways to treat them. A major focus of his studies are monogenic neurological disorders and in particular fragile X syndrome (FXS). FXS is the most common inherited form of intellectual disability and remains without effective treatments options.
The stem cell-based discovery platform established and knowledge gained as part of Dr. Pouladi's program have the potential to advance therapeutic development for not only FXS, but also other neurodevelopmental disorders.
Cells in our body are constantly engaged in physical interactions. They stick together, squeeze through each other, and each possesses a primitive sense of touch. These physical interactions are crucial in processes that control how we grew from a single cell into a complex organism and how they function. In diseases from cancer to neurodegeneration to chronic inflammation, these mechanical regulatory mechanisms are interrupted or impaired, causing cells to lose control and wreak havoc in our body.
The research proposed here aims to understand the changes to mechanical interactions in diseases down to the molecular scale. To do so, we need to develop tiny molecular tools that will allow us to look at these mechanical interactions through a microscope and control them with drugs.
We will build these tools using the latest DNA nanotechnology, which gives us predictable control over the shape and function of these molecules. We will apply these tools to understand how cancer metastasize to a new place in the body and how neurons break connections in neurodegeneration. This will help us identify drug targets towards a cure to two major diseases with high impact to the health of people in our society.
By 2040, 25% of Canadians will have osteoarthritis (OA), a disabling joint disease. This number will be as high as 50% for those who hurt their knee playing youth sport. Currently, the treatment of youth sport knee injuries focuses on return to sport. Few seek care beyond their injury, and little effort is made to prevent OA. Stop OsteoARthritis (SOAR) is a new physiotherapy program to reduce the risk of OA after a youth sport knee injury.
Designed with a team of patients, clinicians and researchers, SOAR teaches active youth how to manage their OA risk, and improve knee muscle strength and physical activity levels after injury. SOAR consists of a knee camp, personalized exercises, wrist-worn activity-tracker and weekly counselling.
This research will assess what youth with a sport knee injury think about SOAR and how well SOAR works to reduce muscle weakness and inactivity – proven risk factors for knee OA. We will also explore new ways to monitor knee health after injury.
The SOAR team will continue to include patient and clinician partners to make sure that SOAR is practical, and relevant. It is expected that SOAR will improve the health of young British Columbians who have a sport knee injury and reduce their risk for OA.
Acutely ill patients often require life-saving measures including breathing tubes and breathing machines (mechanical ventilation; MV). As our population ages and more people have chronic, complex health conditions, MV is becoming a more common, necessary practice.
Despite medical advances, about 2 out of every 3 adult patients experience swallowing problems (dysphagia) following prolonged MV (>48 hours). Untreated dysphagia decreases quality of life, prolongs hospital stays, and leads to complications such as pneumonia and even death. Early dysphagia identification is key to avoid negative outcomes and high healthcare costs. There is currently no scientifically confirmed way to screen for dysphagia in this population.
To address this gap, my research program will study swallowing in patients following prolonged MV using modern methods, such as airway imaging and tests of breathing, tongue strength and saliva. The results will be combined with patient priorities and other evidence to develop better dysphagia detection methods and personalized treatment approaches.
Ultimately, this will lead to the first scientifically supported screening tool for this population resulting in better health outcomes and reduced care costs.
