The Next Generation of Multifunctional Nanoparticles for Cancer Imaging and Therapy

In photodynamic therapy (PDT), a nano particle (NP), is placed within the body and is illuminated with light from outside the body. Normally, the light that gets absorbed by the NP can produce high energy oxygen molecules which will chemically react with and destroy most organic molecules that are next to them, like tumours. This type of light therapy can also be employed to release small drug molecules from the surface of the NP. PDT can be far less expensive than radiotherapy or surgical operation and post operative care. Furthermore, PDT recovery typically requires hours or days rather than weeks, and does not leave a toxic trail of reactive molecules throughout the body as is the case with chemotherapy. This is because the light is targeted at the precise location of the NPs. PDT therefore, is potentially a non-invasive procedure for treatment of diseases, growths and tumours. Additionally, NPs with multiphoton upconversion properties are useful for the diagnosis and treatment of cancer and hold great promise for biosensing and bioimaging. Dr. John-Christopher Boyer is involved in designing the next generation of multifunctional NPs capable of both imaging and selectively targeting cancer cells using photodynamic therapy based on molecular switches. The ultimate goal of his project is to develop nanoparticles with photon upconversion properties, and apply them in sensitive cancer detection. Consequently, a focus of his current research project is to evaluate the performance of the upconverting NPs when applied to sensitive detection and treatment of prostate cancer. Dr. Boyer’s research could significantly enhance Canada’s position in nanomedicine, and developments in this area may well revolutionise medical practice in cancer detection and treatment over the coming years.

Identification and analysis of proteins required for tubulin homeostasis: impact on nervous system disorders and cancer

A cytoskeleton is a central component of all cells, and is made of protein filaments that assemble into networks. These networks allows cells to divide, change shape as needed and perform a multitude of other vital functions. Microtubules (MTs), are essential cytoskeletal components composed of an elementary protein called tubulin. To fulfill its cellular function, the activity and level of tubulin must be maintained optimally by a process known as homeostasis. This process is not well understood, but is known to be particularly important for nervous system function. In fact, disruption of tubulin homeostasis can lead to neurological problems such as Huntington’s disease. Furthermore, because MTs are important in the uncontrolled division of tumour cells, tubulin represents an important target for cancer treatment. To improve our understanding of the fundamental principles guiding tubulin homeostasis, Dr. Melissa Frederic has undertaken research to identify and characterize proteins associated with the function, organization and maintenance of tubulin, using mainly C. elegans, a tiny worm, and mammalian tissue culture cells as model systems. One protein that will be characterized at the molecular and cellular levels, termed HECTD1, has been identified in her lab as a likely factor influencing tubulin homeostasis; importantly, it has also been linked to neural tube defects in a mouse system where the protein was removed. At the same time, Dr. Frederic is doing genetic screens to identify proteins that effect tubulin homeostasis, including one that utilizes the anticancer drug taxol or benzyl isothiocyanate. Together, the characterization of HECTD1 and the discovery and subsequent characterization of additional proteins implicated in tubulin homeostasis, are expected to shed new light on nervous system disorders such as neurodegeneration and neural tube defects, the most common congenital malformation in humans, as well as cancer.

Perceptual and attentional abnormalities in autism – understanding impaired discrimination of the eyes

Autism is a pervasive developmental disorder involving impairments in social interaction, verbal and non-verbal communication, a lack of imaginative play, and repetitive and restricted solitary activities. A critical goal of autism research is the identification of biological, behavioural and cognitive markers that will help researchers determine the links between genes and autism and aid in the development of effective diagnostic tools, as well as improve upon existing intervention and treatment programs. Of note, abnormal perceptual processing is currently a candidate marker of autism. There is mounting evidence to suggest that people with autism show specific perceptual abnormalities, and that these abnormalities may play a causal role in deficits in social processing. For example, research suggests that individuals with autism show abnormal perception of faces, with a reduced ability to discriminate visual changes to the eye area of a face, as compared with normal perception of changes to the nose and mouth. However, it is unclear whether these abnormalities are due to a deficit in perceiving visual information from the eyes, or a lack of attention to this visual information. Elina Birmingham’s research involves the use of eye tracking and a new methodology called the moving window technique, to measure the focus of attention in children with autism while they undertake visual face exploration. Her research will provide insight into several key questions regarding perceptual and attentional abnormalities as indicators of autism in children. The results of her study will contribute to the goal of identifying markers of autism, and as such may have important implications for treatment and intervention methods.

Social Attention and Visual Exploration in Children with Autism Spectrum Disorders

Autism is a severe neurological developmental disorder characterized, in part, by social impairment. A key social impairment present early in the development of children with autism is abnormal gaze following. Children with autism often do not follow the eye-gaze of others towards objects or events in the environment, which hampers their development of language and social skills. It may be that the seemingly abnormal gaze following evident in children with autism results from abnormal basic attentional responses to gaze cues. Clinical reports suggest that when in object-rich environments, these children demonstrate a diminished ability to focus on socially meaningful stimuli. Therefore, further research focusing on the ability to orient to gaze cues within complex visual environments such as classrooms, is critical. Adrienne Rombough has developed a computer task that examines orienting responses to gaze cues within complex visual scenes. In her current research she is using this program to examine the ability of children with autism to detect changes in complex visual scenes with or without the presence of gaze cues. Her study is designed to compare the performance of school-aged children with autism to that of mental age-matched, typically developing children. Her short term objective is to address the question of whether (and to what extent), the attention orienting response to gaze cues is abnormal in autism. This is the first known study to use an alternative, indirect measure of attention (i.e. change detection), to investigate gaze cueing within complex visual scenes. Over the longer term, Ms. Rombough’s findings could potentially improve the present understanding of how children with autism use social cues to explore their visual environments and how this skill set is potentially related to social impairment. The project is part of a larger research program designed to characterize the cognitive underpinnings of social impairments in autism.

Predictors of Medication Adherence in Renal Transplant Patients: Self-Efficacy, Depressive Symptomology, and Neuropsychological abilities.

Chronic Kidney disease (CKD), is relatively common among middle-aged and older adults and the incidence is increasing. For example, 119 million Canadians had CKD in 1996, while by 2004 that number had reached roughly 154 million. Furthermore, just under 1,000 people received kidney transplants in Canada in 2005, while three times that many remained on wait lists that year alone. Needless to say, the successful clinical management of CKD is dependent on a number of factors. Recently, Ms. Theone Paterson and colleagues have determined that cognitive abilities are impaired in patients with CKD following successful kidney transplant, in a similar way to that seen in patients with CKD prior to kidney failure. Importantly, they also recently found that difficulties completing both traditional and everyday cognitive problems are predictive of decreased medication adherence among renal transplant patients, and that depressive symptoms partially mediate the relationship between traditional cognitive performance and medication adherence. Therefore, the extent to which real world functional issues such as adherence is predicted by traditional and everyday problem solving, depression and self-efficacy is an important issue in renal transplant, for patients, their healthcare providers, and their caregivers. In her current research program, Ms. Paterson is focusing on the relationships among traditional and everyday measures of cognitive performance, general and medication adherence-specific self-efficacy, self-reported depressive symptoms and medication adherence in people who have undergone successful renal transplantation. The results of this work will aid not only in understanding difficulties faced by transplant patients, but also in the development of interventions designed to improve adherence and consequently, real-world functioning for these patients. Additionally, the results of this research will be used to develop sensitive and valid measures to assess real-world function in patients with CKD and ultimately improve their quality of life.