Jessica Sheldon (PhD) is on a mission to starve out Acinetobacter baumannii —one of the world’s most virulent hospital-borne pathogens.

Notorious for its speedy evolution and multi-drug resistance, the hospital-borne bacteria lingers on dry surfaces and infects critically-ill patients, leading to sepsis, pneumonia and high mortality rates.

In this episode, Sheldon delves into the real-life events that drove her to investigate histamine, and its role in bacterial survival and immune response.

In 2022, Sheldon joined the University of Saskatchewan’s College of Medicine as an assistant professor of Biochemistry, Microbiology & Immunology -- something she now laughs about after an ill-fated high school placement in an immunology laboratory.

“Cytokine cascades, pathways, the signaling just got way over my head real fast,” said Sheldon. “I didn’t really know what I was doing.”

Sheldon enrolled at Lakehead University, drawn to the tiny pathogens with outsized roles in movies like Outbreak. She estimates she read the book The Hot Zone 20 times.

Her persistence paid off.

“One of my second year microbiology teachers said, ‘you know, I think you're kind of good at this. Maybe you should try it as a career.’

Sheldon zeroed in on metals and wrote her doctoral dissertation on the role iron plays in the proliferation of bacteria such as Methicillin-resistant staphylococcus aureus (MRSA).

Today, she studies both Morganella morganii and Acinetobacter baumannii —  the multi-drug-resistant bacteria singled out twice in the last decade by the World Health Organization as a ‘priority 1-critical pathogen’.

“I’m perpetually fascinated by the idea that something so small can change the course of history,” said Sheldon. “And we’ve seen that recently with COVID.”

Sheldon was already studying the metal uptake and signalling systems that grow and sustain A. baumannii when the bacteria ripped through hospitals during the pandemic, attacking Covid-infected patients on ventilators.

By 2023, Sheldon landed a five-year CIHR grant of $900,000 to study A. Baumannii and the way it turns histidine into histamine. Her goal is to pinpoint the way the pathogen uses histamine to evade its host, as it sends out siderophores to steal iron and other nutrients.

The compound appears to serve as a signalling mechanism for both the host and the invading pathogen, she said.

“We know the bacteria are using histamine in the synthesis of these molecules to get iron, but they're also secreting it into the environment. We're not really sure why,” Sheldon said.

Her laboratory is working to trace and target those pathways, so researchers can identify and potentially develop new treatments — small molecules or antibody inhibitors that could disrupt multi-drug resistant pathogens.

Beyond A. baumannii, histamine may hold the key to how some of the world's most notorious bacteria grow, spread, and evade immune defences, Sheldon said.

“We're running out of drugs, but there's really not a full appreciation for the fact that we're losing the ability to treat bacterial infections,” Sheldon said. 

“We need to develop supplementary therapies or alternative therapies.”

Kirk Haan graduated from high school, thinking he’d study pharmacy at the University of Saskatchewan, and walk out five years later.

After one summer at a pharmacy, Haan realized he was after a more ‘hands-on’ career in medicine.

“I’ve kind of worked with my hands my whole life, just between rummaging around on a farm and always kind of building things,” he said.  “Now it’s using them to help people in a direct way.”

Then, Haan found his passion — inside the laboratory.

In 2018, Haan landed a summer position in Dr. Thomas Fisher’s lab, studying osmoregulation — the mechanisms that govern our bodies’ salt and fluid intake and output.

He never looked back. 

By the time he entered medical school, Haan had completed two summer research projects, his honours degree, and his master’s thesis in osmoregulation, all under Dr. Fisher’s supervision.

“He was a really good role model,” Haan said, noting he returned to Fisher’s lab for up to 30 hours a week during his first and second year of medical school. 

Haan is set to resume his work at medical school next summer, after he’s completed his PhD. 

Until then, he and Fisher are unravelling mechanisms involved with Synaptotagmin-11, and later Endophilin-A1, proteins associated with keeping the body’s fluid-salt balance in check.

Changes in those complexes are often seen in patients with neurodegenerative conditions, such as Parkinson’s, ALS (amyotrophic lateral sclerosis) and Alzheimer’s disease.

Dehydration and fluid imbalances also become more common as patients age.

Haan calls this “low-hanging fruit” when patients arrive at Emergency Departments, worried about pharmaceutical interactions.

“The more drugs you take, the more likely you are to have a drug interaction that causes a perturbation in this system,” said Haan.

He believes Synaptotagmin-11 and Endophilin-A1 may play “a massive role” in the long-term regulation of our body fluids.

Haan also credits his wife — who just entered medical school with her own PhD — and an “incredible community” of friends in Saskatoon for their support during his decades-long journey through two academic worlds.

Although they will likely have to leave Saskatchewan to pursue his residency as an ear, nose and throat surgeon, Haan said the plan is to return.

“With some of the things that I've learned and my passion for blending this basic science with clinical medicine, maybe somewhere down the line we find something that's really cool that can really help people,” he said.

Sébastien Gauvrit (PhD) was only ten when his family let him have his first tank of guppies. Within weeks, he was hooked.

“I actually had to understand genetics directly by mixing these different fish together to get the colour or fin shape I was interested in,” said the vascular biologist and genetic modelling pioneer.

From his home in France, to post-doctoral work pioneering new models for vascular disease in Germany, to his current position as an assistant professor of Anatomy, Physiology and Pharmacology at the University of Saskatchewan’s College of Medicine —  tropical fish tanks remain a constant in Gauvrit’s life.

 

This year, two grants from the National Sciences and Engineering Research Council of Canada (NSERC) totalling $340,000 mean Dr. Gauvrit will expand the University of Saskatchewan’s zebrafish aquariums — and refine his laboratory’s modelling work and research on vascular development.

 

Zebrafish are transparent in their first hours and days, which allows scientists to watch them forming vascular cells in real time.

 

“Most genes that trigger vascular disease in humans are present in zebrafish,” Gauvrit said, noting they share 70 per cent of of their genes with humans.

 

Using both fish and rodent models, Gauvrit will do a deeper analysis of the transcription factor HHEX [Hematopoietically Expressed Homeobox], because of its cascading effect on the cells that eventually determine lymphatic health.

 

“If you understand how this gene regulates others, we can identify new genes involved in lymphatic disease, and understand a bit more the process behind all these events,” Gauvrit said.

He’s also looking at VEGF-A [vascular endothelial growth factor], a gene implicated in vascular diseases, including age-related macular degeneration [AMD]. Right now, patients with blurred vision and an overgrowth of blood vessels are treated with multiple injections to the eye, with the hope of limiting damage.

“A high proportion of patients develop resistance against this therapy, which is a big issue,” Gauvrit said. “It’s also very costly.”

 

Mice die quickly without VEGF-A, but zebrafish without it survive — even thrive. Gauvrit wants to know what processes help zebrafish compensate, and where mammalian cells diverge.

Gauvrit said the broader implications of vascular research will have ripple effects in treating lymphedema, strokes, and age-related macular degeneration.

“We still discover new things,” Gauvrit said. “Just by serendipity and by randomness, sometimes you can find a bit greater science than when you have a very specific question.”

Stuart Skinner (MD) knew something was wrong three years ago, when patients started coming to him with vision loss, fever, rashes, and meningitis.

Almost every case could be traced back to untreated syphilis — a sexually transmitted infection with caseloads exploding 1,200 per cent from 2017.  Saskatchewan saw this spike just as Covid-19 entered the picture.

“With the pandemic, testing dropped dramatically,” Skinner said, noting this wave of syphilis entered north-western Saskatchewan from Alberta, often travelling alongside HIV. Syphilis often spreads through sores, and can remain unnoticed for months or years on end, making early detection difficult.

“If you don’t see it, you won’t be seeking care for it."

 

When the infectious diseases physician and the Wellness Wheel team began treating mothers with severely ill newborns, stillbirths and birth defects, Skinner knew he had to act. Treating syphilis usually means a series of clinic and laboratory appointments, followed by intramuscular Bicillin injections, and intense contact tracing.

Instead, Skinner, Dr. Sean Rourke, Cara Spence and their teams pared that down to a one-hour stop.

They approached tribal councils and Indigenous-led health organizations, asking for help setting up mobile locations where anyone could be tested, diagnosed, and offered treatment. 

Nursing teams drove vans to powwows, festivals, even pharmacies, offering quick, confidential finger-prick tests and results.

“The whole concept was to be flexible and mobile and adaptable . . . . so that we weren't the barrier,” said Skinner. “It wasn't easy for the nurses to set up and read the results or draw the blood in a less comfortable environment, but they did an amazing job.”

 

In Saskatchewan, a total of 1,797 people agreed to be tested, uptake Skinner calls ‘phenomenal’. Roughly three per cent were infected with HIV; 16% had syphilis.

“The majority were willing to get treated right then and there,” Skinner said.

Those teams have now visited more than 50 locations across the prairies, through a $4M national partnership called the ‘Ayaangwaamiziwin’ Centre — which translates to ‘be careful, be prepared’ in Anishinaabe. Health officials and private donors recently extended those grants for an additional year.

Skinner's colleagues keep fielding requests for the point-of-care service, which in turn has created a network of trusted Indigenous health leaders. This web, he said, could create the backbone of targeted outreach and screening for other diseases, such as diabetes or cancer.

 

But it only works with mutual respect, he warned.

“This isn't going to First Nations just to help them,” Skinner said. “I've learned so much from the cultural values that are built on what happens in First Nations. We have a lot to learn."

Skinner said mutual respect also means predictable paycheques — not just the odd grant.

He said health budgets need to pay for health promotion workers employed at Indigenous-run organizations and non-profits, the ones who stick around after the testing van leaves. Patients are more likely to stay in touch with familiar faces and staff, he said.

“It’s about respect, kindness, and building trust,” he said. “That is really critical.”

Yi-Chun Chen (PhD) is taking a close-up look at some of the body’s hardest-working cells — the ones often processing an overabundance of modern-day food and nutrients.

“From an evolutionary point of view, our cells are not designed to deal with that,” said Chen, who joined the department of Anatomy, Physiology, and Pharmacology at the University of Saskatchewan last year as an assistant professor.

She said our bodies are pushed into churning out large amounts of insulin rapidly after snacks and meals, “which makes the beta cells work extra hard.”

Raised in Taiwan and inspired by her grandfather—a retired elementary school science teacher—Chen’s fascination with biology first led her to work as a medical laboratory technologist, then to the world of cellular research.

Using both rodent and human models, Chen is studying pancreatic beta cells: the way they process peptide hormones like insulin and how their behaviour and function is affected by an excess of nutrients.

With high-resolution imaging, she and her team are examining how both humans and mice synthesize, process, and clear peptide hormones.

“There are a lot of things we still don't know about peptide hormones, not just in the pancreas, but in the brain, in the gut,” she said. “Those are fascinating.”

Last year, Chen was the recipient of a Canadian Institutes of Health Research Research Excellence, Diversity, and Independence Early Career Transition Award. After moving from UBC to Saskatoon, Dr. Chen said feels considerable support already from her established and mid-career prairie colleagues.

“They can mentor us and guide us, and we also have a group of five or six young scientists,” she said. “I can envision myself working on many, many interesting projects with them.”

Her goal today is to identify biomarkers that could predict diabetes far earlier.

She hopes to develop biochemical assays that measure proinsulin levels to serve as an early warning system. This could enable interventions months or even years before a traditional diagnosis based on blood glucose levels.

“We want to be able to predict the development of, for example, type 1 or type 2 diabetes before they are diagnosed,” said Chen.

In the long term, Chen envisions both preventative strategies and regenerative therapies to fight diabetes. Stem cell-derived beta cells may be a future solution, she said.

“We are making really good progress in Canada, actually. We have clinical trials. We’re putting the stem cell–derived beta cells into patients with type 1 diabetes.”

She hopes this will one day reduce the need for constant insulin injections, even helping curb  obesity.

“Don’t give up,” Chen said. “We are passionate and we want to work on many, many things.”

“If you like it, keep going.”

James Stempien (MD) has navigated some of the most challenging corners of emergency medicine, from the frigid isolation of Inuvik to the bustling corridors of Saskatoon’s emergency departments.  His experience in low-tech outposts has shaped his approach to modern emergency care.

 

“When things aren’t going well you see it in the emergency department first,” Stempien said. “We’re the front door. We’re always open.”

 

As provincial department head of emergency medicine, Stempien sees patients on their worst days in hospitals bursting at the seams, struggling to keep pace with Saskatchewan’s growing population.

 

“I worked in emergency last night and we were really busy, hours behind. All the ER docs there and nurses were running our tails off,” said Stempien. “We're seeing an increase in acuity.”

 

Stempien said the patients he sees now come in with serious medical concerns, which cannot be written off as minor ailments.

 

One in five emergency patients in Saskatoon requires hospitalization. Amid frequent congestion, Stempien says some find themselves on stretchers in the hallway, even in former linen closets, waiting to move upstairs to an acute care bed.

 

He said while a plan to open 109 more acute care beds at Saskatoon City Hospital ‘will make a big difference’, he and his staff are concerned overcrowding jeopardizes patients in the waiting room, leading to moral injury and burnout.

 

Stempien is determined to free up space inside his department. He's also led numerous innovations aimed at streamlining emergency medicine, including a recent move to send patients their discharge instructions via text message.

 

“They can access it as many times as they want. They're not going to lose the piece of paper on the way to the parking lot,” said Stempien.

 

Stempien, 67, said he still loves the job, in part thanks to the team atmosphere, and also because his patients are still full of surprises.

 

“Many things I've seen thousands of times, but every now and then you run across something and you think, wow, I've never seen that,” he said.

 

“That's what makes emergency medicine interesting. And fun."

As the world aims to eradicate hepatitis C (HCV) by 2030, Carrielynn Lund and Dr. Alexandra King’s team created a how-to guide.

 Journeys to Wellness: Prairie Hepatitis C Roadmap is a step-by-step guide to tackling a spike of new infections across the three Canadian prairie provinces.

Hepatitis C (HCV) causes severe liver disease, and was notoriously difficult to treat until the introduction of direct-acting antivirals a decade ago — antivirals which boast a remarkable 95% success rate.

Despite this advancement, Lund and Dr. King say Saskatchewan, Alberta and Manitoba need to know why HCV cases keep rising, particularly in jails, in remote communities, and in people who lack adequate housing and nutrition.

The virus is not picky, as Carrielynn Lund learned when she was first diagnosed in the 1990s. Her doctor wrongly told her back then the blood-borne illness could be spread only through injection drug use.

Shocked, Lund said “I went out of that room and drove home thinking, oh my God, I'm gonna die.”

A single mother of two, she resumed her professional life and never disclosed that “dark, dirty secret” until nearly 20 years later, as she became friends with Dr. King.

The Waniska team, led by Saydi Harlton, brought together researchers, health professionals, and people who’ve lived with hepatitis C in sharing circles, workshops and interviews.

“The stigma around this needed to be addressed and I wanted to be a part of it,” said Lund. “People often feel really alone in this journey, and it’s so important that we create spaces where they can share their stories and be heard."

Participants identified barriers to care, including confidentiality breaches, misinformation and inadequate access to testing.

“My priority right now may or may not be my hepatitis C. It might be, where am I going to sleep today? Or, what food am I going to be getting?” said Dr. King.

In the Roadmap, King said the disproportionately high number of cases in Indigenous people shows a need for true elimination strategies, rather than pockets of “little pilot projects.”

"There aren't necessarily a lot of resources, so you're dealing with fairly fragile systems," Dr. King noted.

Recent provincial government decisions to axe needle exchanges, and cut public transportation routes to remote and northern communities have taken their toll, she added.

Given the hurdles faced by Indigenous and two-spirit people, both Dr. King and Lund say prairie people need culturally informed care. They point to Indigenous-led hepatitis C elimination strategies with predictable funding and resources.  

“It really helps you to understand the importance of really good evidence-based policy that supports people and meet them where they're at,” Dr. King said.

Lund and Dr. King believe making a fiscal case for early detection and treatment may also swing policy-makers back toward patient-centred care.

Peer support also plays a role, Lund said.

“When someone who has been through it helps a newly diagnosed person, it can truly change everything for them," she said. 

 

Brianne Philipenko (MD) was midway through her respirology fellowship in Calgary when the Covid-19 pandemic shut down the city.

 

She started interval workouts at home using Nike’s fitness app — when inspiration struck.

 

“Coming up with a creative, innovative way to allow people to access an exercise program outside of the typical organized pulmonary rehabilitation in a gym setting was something that I became really interested in,” said Philipenko..

 

As a respirologist, Philipenko was already frustrated by the lack of ‘mainstay’ guidelines on incorporating exercise into severe asthma treatment.

 

“I think that’s a big disservice for our patients,” she said. “We’re giving them these fancy medications that improve their asthma, but we’re not going after the low-hanging fruit such as physical activity.”

 

“It's something cheap, accessible, that everyone can do, and it's something that I think is very much underutilized.”

 

Even before the pandemic, access to pulmonary rehabilitation programs was severely limited, as most also serve with people suffering from Chronic Obstructive Pulmonary Disease (COPD). Philipenko’s asthma patients were often leery of exercise, for fear of triggering an attack. 

 

“You don't exercise, so then you get out of shape and that makes you more short of breath when you exercise,” she said. “It becomes a vicious cycle of deconditioning and fear."

 

Philipenko teamed up with a physiotherapist and a kinesiologist to develop an at-home rehabilitation program for people with pulmonary hypertension. Patients download an app, then follow the program for eight to 12 weeks, incorporating pacing strategies and breathing exercises to ease their way back into fitness. 

 

“We're still in the middle of recruitment,” said Philipenko. “We have people that are extremely fit exercising every day, to people that never exercise ever, with asthma participating in the study,” she said. “It's promising.”

 

By 2021, Erika Penz (MD) and Donald Cockcroft (MD) -- colleagues Philipenko met during internal medicine training — helped convince her to return to her hometown, taking on her current role as a respirologist and an Assistant Professor of Respirology, Critical Care and Sleep Medicine at the University of Saskatchewan's College of Medicine. 

 

“They have been giants in the space of asthma, and they really inspired me. They brought me back and made it exciting to participate in the research scene here in Saskatoon,” Philipenko said.

 

She’s working with the Asthma Research Lab team, where her patients can now take part in bronchoprovocation studies and pharmaceutical clinical trials.

 

“As much as I love my clinical practice, it's really nice to have something else going on that shakes things up. And for me, that was research,” said Philipenko.

 

She hopes to see a shift in the way exercise is perceived, pushing for recognition of its critical role alongside pharmaceuticals.

 

“That's the wonderful thing about asthma, is that if it's controlled, you should be completely asymptomatic. It's not a progressive disease. And we have some medications that can achieve that for people now. So it's a pretty exciting time to be working in this field.”

In this episode, we gain insight into Dr. Sarah Forgie, the new Dean of the College of Medicine. She discusses her innovative teaching methods, her career as a pediatric infectious disease specialist, and her vision for advancing Saskatchewan’s College of Medicine.

Dr. Forgie also shares the story behind her decision to learn the ukulele.

Born to family physicians, Dr. Forgie grew up in Lynn Lake, Manitoba, a remote fly-in mining community. Her family later relocated to Winnipeg, where Dr. Forgie credits much of her motivation to her mother, who encouraged her to pursue both medicine and leadership roles.

As a pediatrician and professor at the University of Alberta, Dr. Forgie’s journey into university leadership can be traced back to her willingness to deploy creative teaching methods. Faced with the challenge of teaching infectious diseases to first-year medical students, she re-wrote the Talking Heads hit “Psycho Killer” to reinforce best practices in treating Streptococcal pharyngitis -- with ukulele accompaniment.

It worked. Those who attended her “Take Five” bacteriology lectures at the University of Alberta retained 98% of the key concepts, compared to a 50-60% retention rate among students in standard classes.

Dr. Forgie strived to instill strong clinical reasoning, and challenged her students to present key concepts in their own creative ways.

“With every session, I would do something, they would do something, and it just made it a fun environment,” she said.

Following her appointment as Saskatchewan’s first full-time female Dean of Medicine on July 1, 2024, Dr. Forgie returned to clinical service this fall as a pediatrician at the Jim Pattison Children’s Hospital in Saskatoon.

In her role as Dean, she aims to strengthen connections between the College of Medicine and Saskatchewan’s medical practitioners.

“What I would love to see in Saskatchewan is that every physician approaches their work with an academic lens,” Dr. Forgie said. This 'lens' may encompass participating in clinical trials, exploring ways to alleviate physician workloads, or collaborating with learners, she said.

Engagement with Indigenous communities remains a critical component of Dr. Forgie’s vision for wellness.

“I am all about collaboration... with First Nation, Inuit, and Métis communities to better prepare our trainees to work within these communities,” she stated, affirming her commitment to cultural sensitivity in healthcare.

As a lifelong resident of the prairies, Dr. Forgie understands the isolation often experienced in rural medicine. She aims to foster connectivity among healthcare providers and new learners.

“How can we help and how can we reduce some of those feelings that you're having around burnout and frustration?” she asked. “Helping with that leads to a virtuous cycle of how do we make things better in Saskatchewan?”

A behavioural neuroscientist in Saskatoon is uncovering marijuana’s effects on fetal brain development. 

After recently winning a five-year CIHR grant of $960,076 in the spring of 2024, Dr. John Howland’s lab at the University of Saskatchewan is expanding its work examining prenatal exposure to cannabis smoke. Howland’s teams will assess the way cannabis exposure alters higher brain functions like memory and learning in both rats and mice.

Compared to cannabis injections in the past, the professor of Anatomy, Physiology and Pharmacology at the College of Medicine said exposing rodents to high-potency smoke for up to 15 minutes at a time provides a more realistic picture of marijuana's effects on fetal brain development. 

Over their lives, Howland will measure changes in cortical limbic circuitruity, for both rodent mothers and their offspring. 

“The cortex is definitely involved, but we also look at other areas like the hippocampus and the amygdala,” said Howland. “There’s pretty good evidence that they are at least subtly affected after gestational exposure to cannabis.”

Now, it’s a matter of quantifying which circuits cannabis affects in the rodent brain — under circumstances as close to real-life human exposure as Howland's laboratory can create. 

"It's not simple," said Howland. He notes a wide variety of phenotypes of THC and CBD strains are now available at retailers, each with its own characteristics and potential interactions with neurons. 

“These receptors are involved in many discrete events during brain development,” he said. "We're hoping to be more controlled and more specific." 

Howland's team is also searching for ways to stem damage from high-potency strains, while exploring therapies like exercise to counteract cannabis exposure and help future generations grow healthier brains.   He said cannabis may be legal -- but that does not make it safe.

"It turns out a lot of things that are legal like alcohol and tobacco aren't that safe during pregnancy either," said Howland.

"I think more knowledge has to be helpful as women make these decisions for themselves.”