It focuses on whether certain genes are switched on (activated) or switched off (silenced) inside cells.

“Every person has the same DNA in all their cells, but only certain genes are activated in each cell, depending on that cell’s type and role,” says the associate professor in the College of Pharmacy.

“For example, for a cell in the stomach lining to function properly, it has to keep particular genes activated and others silenced.”

If something goes wrong with this process, it can cause disease. In fact, some cancers are caused by changes in gene activation. About nine years ago, when Lakowski was a post-doctoral researcher at the University of British Columbia (UBC), the drug industry was starting to produce drugs to influence these epigenetic processes.

“From my basic understanding of epigenetics, I thought this was going to be potentially disastrous,” Lakowski says. “I thought we needed a way to take the good intentions of the drug industry and refocus them, so drugs didn’t work indiscriminately on multiple genes.”

Today, Lakowski believes he is the only Canadian researcher working to target drugs at specific genes to influence the epigenetic process – an approach that is expected to be more effective and cause fewer side effects than current therapies. He is developing drugs to treat leukemia and gastric cancer by activating or silencing certain genes.

“The philosophy in my lab is that if the drug doesn’t need to go to all those other genes, why don’t we just target it to the handful of genes that are causing the disease?” he says. “That’s the technology we’re developing.”

A research team led by Lakowski was recently awarded $700,000 by the Canadian Institutes of Health Research for a study testing this approach.

“In mouse models and human cells, we’re going to target drugs to a gene called HOXA9 that is known to cause some types of leukemia. This will silence the HOXA9 gene, killing the leukemia cells, but without harming healthy cells.”

Lakowski, who grew up in Vancouver, earned his B.Sc. (Pharm) in 1999 and his PhD in 2006, both at UBC.

Things lined up perfectly for him to join UM in 2012. The College of Pharmacy was looking for someone with his expertise, and he needed a mass spectrometer, which UM was planning to purchase.

“All the stars aligned,” he says. “We use the mass spectrometer to measure how well our targeted drugs work.”

Lakowski is driven by discovery. “I love finding out something that nobody else knows,” he says. “I love it when you see those results come together, because science can be demoralizing.

“You do something and you get a result that’s not right. You keep doing it over and over, and you wonder, ‘Why am I doing this?’ And then one day you pick the permutation that works, and you get the result that works. And you’re just like, ‘That’s why I do this job.’”

“Congratulations to the successful applicants in the Fall 2020 round of funding. This is an impressive showing by UM investigators,” said Dr. Peter Nickerson, vice-dean research of the Rady Faculty of Health Sciences. 

“Some of these projects focus on improving the lives of people with conditions such as kidney disease, Type 2 diabetes and mental health disorders. Others are lab studies that will advance knowledge about illnesses such as Ebola, leukemia, HIV and metabolic diseases.

“Our researchers are also analyzing data to reveal new evidence about interlinked social and health factors in Manitobans’ lives. And they’re studying areas such as Indigenous-led wellness programs and children’s rehabilitation knowledge sharing in order to identify and build on strengths.”

UM Today recently reported on two of the funded projects, which relate to COVID-19: a randomized trial of a home monitoring platform for patients with chronic kidney disease, led by Dr. Claudio Rigatto, and a study of the lived experiences of families with children who are immunocompromised, led by Dr. Roberta Woodgate.  

Here’s a look at the other projects:

Dr. Clara Bohm, associate professor, internal medicine, Max Rady College of Medicine

Grant: $439,874

Bohm’s team will conduct a randomized trial to assess whether stationary cycling during kidney dialysis treatments reduces heart “stunning” (poor pumping, which can cause heart damage) and improves symptoms such as fatigue. The trial involves participants in Canada, the U.S. and Australia.

Dr. Shay-Lee Bolton, assistant professor, psychiatry, Max Rady College of Medicine

Grant: $100,000

Bolton will evaluate whether a psychotherapy and mindfulness program that is delivered virtually helps public safety personnel, such as police officers and firefighters, cope with stress, maintain mental wellness and remain resilient.

Dr. Dan Chateau, assistant professor, community health sciences, Max Rady College of Medicine; research scientist, Manitoba Centre for Health Policy (MCHP)

Dr. Marni Brownell, professor, community health sciences, Max Rady College of Medicine; associate director, research, and senior research scientist, MCHP; researcher, Children’s Hospital Research Institute of Manitoba (CHRIM)

Grant: $432,226

Chateau’s team will use health data to investigate the effects of prescription opioid and psychotropic medication use during pregnancy, looking at patterns of prescription opioid use, short-term effects on children exposed in the womb, and longer-term outcomes for these children.

Dr. David Collister, assistant professor, internal medicine, Max Rady College of Medicine

Grant: $100,000

Collister’s project is a trial comparing oral and topical nabilone (a synthetic form of cannabis) to placebos to determine whether nabilone is safe and effective at reducing itching in patients who are on dialysis for kidney disease.

Dr. Shyamala Dakshinamurti, professor, pediatrics and child health, Max Rady College of Medicine; researcher, CHRIM

Grant: $784,125

This study looks at newborn pulmonary hypertension, which prevents some babies from getting enough bloodflow to their lungs. By focusing on a system of signals in the body called the adenylyl cyclase pathway, Dakshinamurti aims to help these infants’ lungs relax and hearts pump strongly.

Dr. Allison Dart, associate professor, pediatrics and child health, Max Rady College of Medicine; researcher, CHRIM

Dr. Brandy Wicklow, associate professor, pediatrics and child health, Max Rady College of Medicine; researcher, CHRIM

Grant: $1,300,500

Dart and Wicklow will study biopsychosocial risk factors for worsening kidney disease in children and teens with Type 2 diabetes. They will also test a skills-based mental health program to help Indigenous youth with Type 2 diabetes manage their emotions and their disease.

Dr. Andrew Hatala, associate professor, community health sciences, Max Rady College of Medicine; researcher, CHRIM

Dr. Sabina Ijaz, family physician; Giigewigamig health advisor

Elder Dave Courchene, founder, Turtle Lodge

Grant: $1,748,025

This team will conduct an Indigenous-led study of the Turtle Lodge in Sagkeeng First Nation as a model of Indigenous education, wellness and flourishing. The objectives include developing a framework for stronger relationships between Indigenous Knowledge Holders and biomedical practitioners.

Dr. Jason Kindrachuk, assistant professor, medical microbiology and infectious diseases, Max Rady College of Medicine; Canada Research Chair in molecular pathogenesis of emerging and re-emerging viruses; researcher, CHRIM

Grant: $726,750

Kindrachuk’s project focuses on the fact that some men who have recovered from Ebola continue to carry the virus in their reproductive tracts. The study will investigate how the virus persists in the testes and is sexually transmitted. It will also look at Ebola’s long-term effects on reproductive health.

Dr. Ted Lakowski, associate professor, College of Pharmacy

Grant: $699,975

Lakowski’s study aims to develop new cancer therapies that target the specific genes involved in a type of leukemia. These treatments are expected to be more effective and cause fewer side effects than current therapies. The strategy could lead to gene-specific treatments for other cancers.

Dr. Lyle McKinnon, assistant professor, medical microbiology and infectious diseases, Max Rady College of Medicine; researcher, CHRIM

Grant: $100,000

McKinnon will study the role of regulatory T cells, a type of immune cell, in controlling female genital inflammation. Because this inflammation puts women at higher risk of HIV infection, the study is relevant to finding better prevention strategies for women who are at risk of HIV exposure.

Dr. Suresh Mishra, professor, internal medicine, Max Rady College of Medicine

Grant: $100,000

Mishra will focus on prohibitin, a protein that plays an important role in sex differences in fat and immune cells. Using mouse models, he will investigate why men and women display differences in susceptibility and resistance to metabolic and immune diseases.

Dr. Rae Spiwak, assistant professor, surgery, Max Rady College of Medicine

Grant: $60,000

Spiwak will use Manitoba data to investigate what social factors place children at greater risk for physical injury. The study will look at a cohort of children who were hospitalized for traumatic physical injury and compare them with uninjured children, examining factors such as parental socioeconomic status and education.

Dr. Elizabeth Wall-Wieler, assistant professor, community health sciences, Max Rady College of Medicine; research scientist, MCHP; Canada Research Chair in population data analytics and data curation

Dr. Marilyn Bennett, assistant professor, Faculty of Social Work

Dr. Marni Brownell, professor, community health sciences, Max Rady College of Medicine; associate director, research, and senior research scientist, MCHP; researcher, CHRIM

Dr. Marcelo Urquia, associate professor, community health sciences, Max Rady College of Medicine; research scientist, MCHP; Canada Research Chair in applied population health

Grant: $393,976

Wall-Wieler’s team will analyze Manitoba data to determine whether parents with specific health conditions are more likely to have a child taken into care, and how having a child taken into care affects parents’ health. The study will compare First Nations, Métis and all other Manitoban parents.  

Dr. Jun-Feng Wang, associate professor, pharmacology and therapeutics, Max Rady College of Medicine

Grant: $623,475

Wang will investigate the role of a protein, Txnip, in chronic stress-induced neuronal dysfunction. The research will use an animal model for depression, aiming to determine if inhibiting Txnip could be used in treating human depression.

Dr. Brandy Wicklow, associate professor, pediatrics and child health, Max Rady College of Medicine; researcher, CHRIM

Grant: $100,000

Wicklow will examine beta cell and kidney function in First Nations children whose mothers were diagnosed as children with Type 2 diabetes. The offspring will be studied in early childhood and compared with children not exposed to Type 2 diabetes in the womb. The results will contribute to strategies for early intervention.  

Dr. Kristy Wittmeier, assistant professor, pediatrics and child health, Max Rady College of Medicine; researcher, CHRIM

Grant: $100,000

Wittmeier’s team will study how knowledge about research and treatments is shared via networks between researchers, therapists and families of children with development or rehabilitation needs. The goal is to identify strengths and gaps in these knowledge-sharing networks and make recommendations to improve them.

Dr. Roberta Woodgate, distinguished professor, College of Nursing; Canada Research Chair in child and family engagement in health research and healthcare; researcher, CHRIM

Grant: $761,176

Woodgate’s study will involve young immigrants and refugees in co-designing culturally sensitive mental health supports for youth like themselves. Parents and community-based organizations will also participate. The researchers will develop a digital mental health self-management prototype.

Dr. Sheryl Zelenitsky, professor and researcher in the College of Pharmacy at the Rady Faculty of Health Sciences, recently received an Allied Health Research Grant from the Kidney Foundation of Canada for $100,000 to develop dosing recommendations for antibiotics in hemodialysis patients.

Zelenitsky’s study aims to optimize the dosing of the antibiotics cefazolin, ceftazidime, and ciprofloxacin that are commonly used in the treatment of serious, often life-threatening infections in hemodialysis patients. The multi-disciplinary study will see her working collaboratively with nephrologists, renal nurses, and pharmacists at St. Boniface Hospital, where she has a cross appointment.

Zelenitsky’s area of research is in antibiotics and infectious diseases and her specialty is on optimizing therapies for high-risk patients. She teaches antibiotics and infectious disease in the College of Pharmacy undergraduate and graduate programs.

“My idea for this project goes back a couple years when I looked into the data for dialysis patients and realized how little there was on how we should be using these drugs,” she says, “It surprised me at how little there was supporting clinicians in choosing the right doses of these important antibiotics.”

Zelenitsky completed a one-year audit at the St-Boniface Hospital’s hemodialysis unit and looked at the type of antibiotics that were prescribed.

“I reviewed the literature and these antibiotics were essentially being dosed without any data, so they’re really best guesses. And in dialysis patients, antibiotics are often dosed by protocol, so everyone gets the same dose,” she says.

The “one-dose-fits-all” approach means patients get the same dose regardless of age, gender, body weight, or dialysis factors. Zelenitsky also found a lack of consistency in dosing guidelines from location to location.

In Zelenitsky’s study, blood samples will be collected from 60 hemodialysis patients in St. Boniface Hospital who are receiving therapy for suspected or confirmed infections. The samples will be taken to the Apotex Centre’s pharmaceutical analysis laboratory (PAL) where Zelenitsky’s co-investigator associate professor and PAL director Dr. Ted Lakowski will measure the antibiotic concentrations. Pharmacokinetic and population modeling will be used to analyze the data and translate it into practical dosing guidelines for patients.

According to the WHO, antibiotic resistance is one of the most serious threats to global human health, and dialysis patients are among the most vulnerable. They tend to be more prone to infections because of their underlying renal dysfunction and accompanying health issues such as diabetes. They are also at higher risk of resistant infections and more likely to fail therapy. A further complication is that dialysis patients handle drugs differently because of their renal disease.

Zelenitsky hopes that the study will help to establish protocols that will effectively treat dialysis patients in a way that doesn’t promote more antimicrobial resistance.

“The goal is to develop evidence-based dosing guidelines for these very important antibiotics, so we know that we’re achieving effective levels in dialysis patients. If what we’re using now is not optimal, we’ll recommend what should be done based on our study.”