Journal of Biological Chemistry Publication

| 10 October 2025

Congratulations to Ivan Shapovalov for his recent publication in the Journal of Biological Chemistry which describes a combination of elegant in vitro biochemical structure-function studies and in silico modeling to explore the potential of inhibiting the Calpain-1 and Calpain-2 proteases by disrupting interactions between their catalytic and regulatory subunits.

This study included a collaboration with Dr. Emil Alexov from Clemson University in South Carolina and two of his PhD students who performed virtual in silico screens of large chemical libraries to identify small molecules with the potential to bind at the interfaces of the Calpain catalytic and regulatory subunits and thereby inhibit these proteases. Ivan and Victoria Lewtas then used biochemical approaches to measure the affinities of the Calpain subunit interactions and test the ability of selected hits from the virtual screen to block those interactions and inhibit protease activity.

This work forms the foundation of ongoing studies to develop allosteric inhibitors of Calpain that can be tested in pre-clinical models of cancer. They hope this will translate to clinically effective calpain inhibitors that can suppress the metastatic behaviour of cancer cells and improve the survival of patients with aggressive cancers.

This work was supported by a grant from the CIHR. Read their published work here: Quantification and structure–function analysis of calpain-1 and calpain-2 protease subunit interactions - PMC

Cells Publication

News

| 10 October 2025

Congratulations to Danielle Harper and Ivan Shapovalov for their recent publication in Cells, which validates the Calpain-1 and Calpain-2 proteases as potential therapeutic targets whose inhibition could provide protection against metastasis in aggressive tumors like triple negative breast cancer.

With contributions from previous trainees, James MacLeod, Jenny Min and Samantha Cockburn, Dani and Ivan used gene editing to knock out and then rescue expression of these classical calpain isoforms in human breast cancer cells and then evaluate the effect of this genetic manipulation on their ability to form metastatic tumors in xenograft mouse models. They show that genetic loss of Calpain-1 and Calpain-2, or their pharmacologic inhibition, compromises the ability of these cancer cells to migrate in vitro and to metastases in vivo from tumors to the lungs after orthotopic engraftment into the mammary glands of mice.

These studies provide the target validation justification that Ivan is using to move ahead with the development of calpain inhibitors suitable for translation to the clinic. Suppression of the metastatic ability of cancer cells could have an enormous impact on the survival of cancer patients with late-stage disease.

This work was supported by a grant from the CIHR. Read the published work here: Calpain-1 and Calpain-2 Promote Breast Cancer Metastasis - PMC

Cancer Research Publication

News

| 10 October 2025

Congratulations to Brian Laight, Danielle Harper, Natasha Dmytryk and Connie Zhang for their ground- breaking Cancer Research paper showing that the FES protein tyrosine kinase plays an immune checkpoint role in antigen presenting cells which makes it a potential therapeutic target to enhance the efficacy of immune checkpoint inhibitors like anti-PD1 which work on the T cells.

Brian assembled an impressive team of collaborators from within and beyond the lab to support his findings using genetic mouse engraftment models.

Brian has returned to medical school to continue his progress through the MD-PhD program. Connie has moved on to a position in industry, Natasha has entered medical school, and Dani is in the last stages of her PhD with plans to purse a PDF in the UK. This research project is continuing with new MSc student Julian Simonetti and research associates Yan Gao and Changnian Shi, with engagement by two eager undergraduate students Alisha Varty-Higgs and Steph Trandafir.

This work was supported by grants from the CIHR and the Canadian Cancer Society. Read their published work here: Fes-Deficient Macrophages Prime CD8+ T Cells to Stimulate Antitumor Immunity and Improve Immunotherapy Efficacy | Cancer Research | American Association for Cancer Research.

Research Mentorship Program

Spotlight

| 24 September 2025

Our mentorship program, in partnership with the Queen’s Four Directions Indigenous Student Centre since 2016, aims to share knowledge, expertise, and enthusiasm between grade-school youth and Queen’s graduate students. Our mentorships are a collaboration led by the interests and goals of our mentees with relevance to their own community. We aim to foster inquiry and problem-solving skills through scientific discovery to help equip our mentees for success in their career pursuits.

During winter term 2025, we were privileged to offer eight weekly sessions in general science and human health to 24 students including Indigenous students from grades 5-12 at the Katarokwi Learning Centre (KLC) in Kingston, ON. The wide variety of projects offered was based on our mentees’ interests, and included roller coaster physics, blood and ABO typing, exploring the human body with plastinated specimens and clay models, a microscope discovery day (viewing human tissues and plant, microscopic aquatic life, assorted bacteria, and other samples), terrarium ecosystems, model volcanos, the chemistry of slime and much more!

Our final presentation session had our Indigenous Liaison, Monica Garvie (Biological Sciences), lead a brief discussion on the importance of land to Indigenous culture. Afterwards, mentees made posters of their projects with their mentors, shared their favorite activities, and engaged in reflections. Finally, our Indigenous mentees enjoyed a field trip on June 11th to Lake Ontario Park where they visited the Indigenous Manidoo Ogitigan spirit garden. The day included a nature bingo scavenger hunt and a paleolimnology (the study of lake sediments to reconstruct past environmental conditions) simulation, using a delicious cake to represent different sedimentary layers in a lakebed, led by Moncia Garvie. Great fun was had by all!

Working alongside the Program Coordinator Lead (Bruce Elliott DPMM) and Program Coordinators (Cyndi Pruss DPMM; Qingling Duan DBMS), our Assistant Coordinators (Doriana Taccardi DBMS; Yasmine Saini DBMS; Marie Boddington DBMS) provided administrative and coordination support. Head Mentor Jamie Would (Biological Sciences) provided guidance and programming support for our graduate student mentors Marco Buttigieg (DPMM), Nicholas Smith (Biological Sciences), Tai Hunter (DBMS), Bruce Masotti (Neuroscience), Sapphire Newman-Fogel (Neuroscience), and Cindy Wen (DBMS). Monica Garvie provided important Indigenous culture sensitivity training and advice for our whole team and shared Indigenous teachings with our mentees in our last two sessions.

We are excited to plan next year, with Cyndi Pruss stepping in as Lead, and Bruce Elliott (founding member) transitioning to an Emeritus role. Since joining us in 2016 as a mentor, and later serving as Assistant Coordinator and Mentorship Lead, Isabelle Grenier-Pleau has completed her time with the program. We are deeply grateful for her years of dedication and wish her all the best in her next adventures. The entire Mentorship Team finds the QRMP program a very rewarding bi-directional learning experience!

We thank KLC Teachers, Bond Strand (Bridge Aazhogan), Dan Blair (Rise), Josh Vivian (Portage), Megan Tidman (Transitions), Tammy Haferman (Links) and Vice Principal Adam Andrecyk for their strong support and guidance. Our program is supported by the Queen’s Inclusive Community Fund.

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Journal of Biological Chemistry Publication

Cells Publication

Cancer Research Publication

Research Mentorship Program

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