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Dr. Peeyush Lala, a scientist with Lawson Health Research Institute and Western University, is a pioneer in the study and treatment of tumors. During his landmark career, the Professor Emeritus and Past Chair of Schulich School of Medicine & Dentistry‘s Department of Anatomy and Cell Biology has identified many locally-produced molecules, which positively or negatively regulate placental invasion of the uterus to maintain the all-important balance required to make a healthy placenta without harming the uterus.

Of those significant findings, a molecule known as decorin (DCN), which is produced by the uterus, was shown to restrain placental invasion and restrict the overall ability of the very placental cells that control maternal blood flow to transfer nutrients to the embryo, and later develop into a large part of the placenta.

Dr. Lala and his team members Pinki Nandi and Mohammad Fyyaz Siddiqui, as well as collaborators Dr. Victor Han, Dr. Genevieve Eastabrook and Dr. Barbra de Vrijer, have now discovered that over-production of DCN by the pregnant uterus is associated with preeclampsia, a condition in expectant mothers characterized by unexpected rise in blood pressure and compromised kidney function after mid-pregnancy. Preeclampsia is a leading cause of death of pregnant women, and sometimes their fetuses or newborns, throughout the world.

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“This discovery is expected to have a significant impact on maternal, fetal and neonatal health,” says Dr. Lala. “It is very difficult to diagnose preeclampsia before clinical signs appear and managing it during pregnancy is extremely problematic, so early detection is crucial to the survival of the mother and her baby.”

Dr. Lala and his research team are currently engaged in a large prospective study with international investigators to validate this biomarker in a larger population of pregnant mothers.

According to the study, which was recently published by The American Journal of Obstetrics and Gynecology, an elevated blood DCN level in an expectant mother during early-mid pregnancy (15 to 18 weeks) can predict preeclampsia, before clinical signs appear. This was shown by a retrospective analysis of plasma samples from 28 control and 28 preeclampsia subjects who were matched for body-mass-index.

“This study shows that DCN is a novel biomarker of preeclampsia that can be used for monitoring pregnant mothers, taking preventive measures and preparing healthcare providers for early intervention,” says Dr. Lala.

The study was assisted by funds received from the Canadian Institutes of Health Research, a Children’s Health Research Institute Translational Research Grant and a Lawson Internal Research Fund grant.

 

Source: Jeff Renaud, Western University

Last week, the Honourable Kirsty Duncan, Minister of Science and Sport, announced an unprecedented investment of more than $588 million through the Natural Sciences and Engineering Research Council of Canada’s (NSERC) Discovery Grants program. 

The successful applications in London include 12 projects funded for Lawson Health Research Institute scientists, through Western University. In total, they will receive $2.3 million in funding over five years. 

“The funding demonstrates our strong and enduring commitment to science and researchers. Since taking office, our government has worked hard to bring science and research back to their rightful place and this historic investment in the discoveries of tomorrow is just one example of how we are achieving this goal,” says The Honourable Kirsty Duncan, Minister of Science and Sport. 

Across Canada, this funding will go to more than 4,850 researchers and students as they pursue their world-leading discovery work. It also includes support for nearly 500 early-career researchers who will bring a diversity of new voices and new insights to their fields.

Local research highlights 

Dr. Jeffrey Carson is exploring the role of photoacoustic imaging as a method for detecting breast cancer. Currently, during the procedure the breast must be submerged in a tank of water to enhance the transmission of photoacoustic waves from the breast to the sensors. 

“The water tank is cumbersome and impractical,” notes Dr. Carson. “Our goal is to eliminate the need for the water tank by detecting the photoacoustic waves through the air without making contact with the breast.” Their hope is that the project leads to the development of a non-contact photoacoustic scanner offering women the opportunity to sit or stand comfortably during breast imaging. “This simple improvement could greatly accelerate the adoption of photoacoustic imaging for breast cancer screening.”

Dr. Carson adds that funding like this provides graduate student trainees opportunities to develop knowledge and skills in engineering, mathematics, and biophysics. “They bring innovative new ideas to the Canadian medical device industry through employment and entrepreneurship.”

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Dr. Rajnikant Patel is developing advanced robotic and intelligent systems for the next generation of systems and devices for minimally invasive surgery and therapy. These reduce trauma and costs while enhancing efficiency and reliability. 

“For us, this funding opportunity is unique because it supports a program of research rather than a project,” says Dr. Patel. “We can explore new areas and directions that will lead to research projects and medical applications. A program that investigates novel robotic and AI technologies fits well with NSERC’s mandate.” 

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Dr. Gregor Reid is leading a revolutionary project that could save the world’s honeys bees, insects that are vital to human survival. 

The intent is to develop an understanding of how lactobacilli strains can counter the most widely used pesticides that are wiping out nature's critically important pollinators. The lactobacilli appear to potentially degrade some of these toxic chemicals and improve the ability of honey bees to fight off early death.   

“NSERC funding gives ideas like this a chance and even though the funding amount is relatively small, it allows graduate students to apply for their own awards and work on the project,” explains Dr. Reid. Students Brendan Daisley and Johnny Chmiel have been awarded NSERC scholarships to work on this important research. 

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Dr. Xiugen Zheng’s project is investigating the role of circular RNA AEBP in the development and function of dendritic cells which are very important immune cells in the immune system. This will provide insights into new molecular and gene regulators, and their impact on the immune system and overall health. 

“NSERC research funding greatly supports us to study the basic scientific questions that are critical for better understanding health problems and developing treatment for diseases,” says Dr. Zheng. 

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Dr. Rudolf Veldhuizen’s laboratory aims to understand how surfactant performs its function at a molecular and biophysical level. Pulmonary surfactant is a material in the lung that allows people and other mammals to breath with minimal effort. You can see this in babies who are born prematurely and have trouble breathing due to the lack of surfactant. 

“Previous work has established a generalized model of how surfactant improves lung function under standardized conditions. This, however, does not explain how surfactant functions in extreme conditions,” says Dr. Veldhuizen. “By exploring conditions in comparative, mechanistic studies we will be able to establish a more universal understanding of surfactant function.” 

This funded work provides a foundation for clinically relevant studies to further explore the role of alterations to surfactant in lung injuries and the opportunities for therapeutic interventions. 

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Dr. Shou Li is developing state-of-the-art machine learning system able to analyze huge amounts of clinical data and provide human level intelligent analysis. This work will enable the prediction of disease onset, progression and prognosis. “It is added value that will lead to more effective and efficient health care,” explains Dr. Li. 

He adds that this funding is supporting a multi-disciplinary research program that combines the strength of multiple teams. “We will look at both the fundamental side of machine learning systems and clinical applications. In this way, we connect basic science with clinical science.”

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Congratulations to all the Lawson scientists who received funding:

• Dr. Dean Betts for Metabolic reprogramming to enhance the generation of canine induced pluripotent stem cells (Physiology and Pharmacology)
• Dr. Jeffrey Carson for Development of non-contact photoacoustic tomography (Medical Biophysics)
• Dr. Louis Ferreira for Multi-Directional Mechanical Testing of Bone using CTCompatible Loading Mechanisms (Mechanical and Materials Engineering)
• Dr. Shuo Li for Innovative Machine Learning for Medical Data Analytics (Medical Imaging)
• Dr. Penny MacDonald for Investigating cognitive functions mediated by ventral and dorsal striatum (Clinical Neurological Sciences)
• Dr. Charles McKenzie for Fetoplacental Molecular and Metabolic Magnetic Resonance Imaging; instalment (Medical Biophysics)
• Dr. Rajnikant Patel for Design and Control of Robotic Systems and Devices for Medical Applications (Electrical and Computer Engineering)
• Dr. Gregor Reid for Detoxification functionality of lactic acid bacteria (Microbiology and Immunology)
• Dr. Rudolf Veldhuizen for Mechanisms of surface tension reduction by pulmonary surfactant (Physiology and Pharmacology)
• Dr. Aaron Ward for Machine learning-based quantitative image, tissue, and clinical data analysis for lesion detection and characterization on prostate cancer imaging (Medical Biophysics)
• Dr. Eugene Wong for Optimization of spatiotemporal-modulated electric fields and fabrication of organs-on-chips for applications in Medical Physics (Physics and Astronomy)
• Dr. Xiufen Zheng for The role of circular RNA AEBP2 in dendritic cells (Pathology)

 

The ability of humans to use language may also be what puts us at the unique risk of developing psychosis, a subset of mental illness characterized by changes in emotions, impaired functioning, and a disconnection from reality. 

Difficulties with communication – both the ability to use language and to comprehend what others are saying – are some of the earliest symptoms. New research from Western University and Lawson Health Research Institute has shown that this may be because in patients with psychosis parts of the brain not meant to process language are trying to perform this complex job. Like a small airport trying to handle all the air traffic from a big hub like Pearson International Airport, some brain regions may be overloaded in psychosis.  

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“The language system seems to be key to understanding this illness,” said Dr. Lena Palaniyappan, the Tanna Schulich Chair in Neuroscience and Mental Health at Western’s Schulich School of Medicine & Dentistry and Scientist at Lawson and Robarts Research Institute. “We don’t yet fully understand how the disorganization of language takes place in patients affected by psychosis.” 

Embarking on a mission to find out, Dr. Palaniyappan worked with a team of imaging scientists at Robarts to perform MRI scans on the brains of patients with acute psychosis. Patients were recruited from the Prevention and Early Intervention Program for Psychoses (PEPP) at London Health Sciences Centre, a flagship clinic that supports young individuals from a very early stage of psychosis. 

The team divided the patients into two groups – those with severe language disturbances, and those whose language symptoms were less pronounced. They found that both groups had weakening of connectivity, or ‘hubness,’ in the part of the brain generally associated with language -- the superior temporal area. The group with more severe language symptoms also showed an emergence of higher hubness in some unexpected regions of the brain that may be compensating for some of the lost connectivity elsewhere. 

“This finding led us to believe that the language problems may occur because the main hubs that are supposed to conduct language are now retired, and so these peripheral hubs, which have no business of orchestrating language as their main function, are picking up the job and aren’t doing it very well,” said Dr. Palaniyappan. 

The researchers hope that by understanding how language becomes disorganized in psychosis, the data can inform new interventions to focus on strengthening the language systems in the brain to reduce or delay psychotic symptoms.  

Using ultra-high-field magnetic resonance imaging at Robarts Research Institute, they were able to look at the entire brain of patients with acute psychosis. Instead of homing in on one specific area, the team looked at 3-D pixels of the brain (voxels) to get a full picture of what was happening in the whole brain and how different areas were interacting. 

Using the airport analogy, Palaniyappan said that if they had only looked at the language area it would have been like only walking into one airport, and not understanding how the reduced traffic in that airport was influencing the air traffic at other surrounding airports. 

“We went in without any expectations, and searched the whole brain,” said Palaniyappan. “This unique approach allowed us to get a picture of the forest rather than a picture of the tree.” 

The study was the first in the world to use this kind of imaging study in patients with acute psychosis who had a wide variety and severity of clinical symptoms.  

“Because of the uniqueness of this patient group, we made sure ample time was given to explain the procedure and what was expected," said Joe Gati, PhD, acting director of the Western Centre for Functional and Metabolic Mapping at Robarts. "The protocol was kept brief and communication with the subject was maintained throughout the procedure. We also ensured that the imaging protocol was optimized to prioritize data collection, keep noise levels as low as possible, and to minimize the amount of time research subjects were required to be in the MRI.” 

The study was funded through an early-career foundation grant from the Canadian Institutes of Health Research and was supported by PEPP. 

Congratulations to Lawson researchers Drs. Elizabeth Finger and Javeed Sukhera, and medical residents Adam (Zeke) Guy and Melissa Schorr, who have received research funding from the Physician’s Services Incorporated (PSI) Foundation. 

The PSI Foundation is a physician-centered non-profit organization that provides funding for medical research, operating grants and education.

As a hospital-based research institute, many of Lawson’s researchers are also clinicians themselves, conducting research alongside clinical care for patients and academic roles with students and trainees. 

Dr. Finger, Scientist at Lawson and Assistant Professor Western University’s Schulich School of Medicine & Dentistry, was awarded the PSI Mid-Career Clinical Researcher Award. She specializes in frontotemporal dementia looking at different treatment options to improve quality of life for both patients and caregivers, as well as ways to better understand the illness in order to prevent it. 

The Research Trainee Fellowship was awarded to Schorr, MD/MSc Candidate at Schulich Medicine & Dentistry who is supervised by Dr. Amit Garg, Lawson Scientist. This Fellowship was also awarded to Guy, MD/PhD candidate at Schulich Medicine & Dentistry, who is supervised by Dr. George Rodrigues, Associate Scientist at Lawson.

“Supporting physicians and surgeons in research training opportunities and clinician-led studies is important in order to harness their unique perspective on research projects that would be the most meaningful to the practice of medicine and conducted in a way that can be quickly translated into care,” says Guy. “I’m thankful for the support from the PSI Foundation.” 

This grant is allowing him to focus on learning different approaches for analyzing clinical data to identify strategies that will enhance the validity and efficiency of analysis in comparative effectiveness research. “This is critical in identifying cost-effective treatment strategies,” adds Guy.

The Mental Health Knowledge Translation Fellowship was awarded to Dr. Javeed Sukhera, Associate Scientist at Lawson and Assistant Professor at Schulich Medicine & Dentistry, for his research program that looks at how patient care for marginalized populations can be influenced by stigma and bias. 

“Our approach to Knowledge Translation involves putting the products of our work directly in the hands of patients, caregivers, and those designing the system. This participatory approach shifts from translation to mobilization, turning research into action through the co-production and democratization of knowledge,” explains Dr. Sukhera. 

“The PSI Fellowship will help move our innovative work on stigma and implicit bias education forward. PSI funding will support a deeper exploration of invisible forms of stigma embedded in policy and practice within health care organizations. We are also co-designing a digital knowledge translation strategy with patients and caregivers to translate the products of our work into innovations in curriculum, policy and program design.”