University of Western Ontario Crest

The Stathopulos Laboratory

Department of Physiology and Pharmacology

Schulich School of Medicine & Dentistry Crest

About Me

Dr. Peter B. Stathopulos completed his BSc in Honours Co-operative Biology at the University of Waterloo. He later graduated with an MSc from the University of Western Ontario in Pharmacology and Toxicology, studying the role of L-arginine transport and nitric oxide production in heart failure. His PhD work in Biology at the University of Waterloo interrogated the folding and thermodynamic stability of mutant superoxide dismutases associated with amyotrophic lateral sclerosis. Dr. Stathopulos completed his post-doctoral training in Structural Biology at the University of Toronto (Medical Biophysics) and the Princess Margaret Cancer Centre, researching the molecular mechanisms underlying the basis for store operated calcium entry regulation.

Today, as an Associate Professor in the Department of Physiology and Pharmacology at the University of Western Ontario, my research group applies structural biology approaches to reveal the molecular mechanisms regulating calcium and magnesium signaling processes in health and diseased states including heart disease, cancer and immunodeficiency. We integrate structural biology with a range of biophysical, chemical biology, pharmacology, computational biology and live-cell methodologies to understand the relationship between protein structure and function of calcium and magnesium handling proteins integral to life and death processes. Ultimately, we envision using this structure-function data for the identification and/or development of new drugs with the potential to modulate these pathways, maintain health and treat disease.

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Research Interests

Mitochondria are widely recognized as cellular "power plants" due to the high production of ATP. However, mitochondrial calcium (Ca2+) uptake can influence cytosolic Ca2+ concentrations, which underlie the most critical signaling pathways in the cell. Remarkably, mitochondrial Ca2+ uptake not only regulates the enzymes that generate ATP, but also drives cell death pathways that can either maintain health or lead to disease. Thus, we are examining the relationships between the structures and functions of the protein machinery involved in regulating mitochondrial Ca2+ uptake.

Magnesium (Mg2+) is the most abundant divalent cation in our cells. This metal ion forms nucleotide and phosphate complexes, mediates the activity of enzymes involved in ATP production and stabilizes countless channels, enzymes and exchangers. Mg2+ not only antagonizes Ca2+ sensors, buffers and signaling pathways but also functions as a signaling ion itself. In this area, our group is studying the molecular mechanisms underlying the primary active movement of Mg2+ into the endoplasmic reticulum (ER) lumen, agonist-induced ER Mg2+ release and the subsequent uptake into mitochondria to regulate the metabolic state and viability of the cell.

ER luminal store-dependent Ca2+ influx through plasma membrane (PM) Ca2+ release-activated Ca2+ (CRAC) channels drives cytosolic Ca2+ elevations. The molecular players that mediate this store-operated Ca2+ entry (SOCE) include the stromal interaction molecules (STIM)s, which sense changes in ER luminal Ca2+ levels, and the Orai proteins, which constitute the PM Ca2+ channel pore. Upon ER luminal Ca2+ store depletion, STIMs oligomerize and translocate to ER-PM junctions, where they bind to and activate the Orai channels, forming CRAC channel complexes. Our laboratory is investigating the molecular mechanisms regulating STIM/Orai function and the modes of dysfunction associated with disease.

Understanding the molecular and structural mechanisms driving the function of the proteins that handle Ca2+ and Mg2+ in the cell will expose novel avenues for their modulation by small molecules in the treatment of heart disease and cancer, which account for ~50 % of all Canadian deaths annually.

KEYWORDS: MCU; LETM1; MRS2; TMEM94; ERMA; STIM; ORAI; SPCA; calcium signaling; Ca2+; Mg2+; molecular pharmacology; structural biology; solution nuclear magnetic resonance spectroscopy; X-ray crystallography; protein folding; thermodynamics; computational biology; protein structure-function; protein dynamics; protein-protein interactions; protein allostery; ion channels; light scattering; optical spectroscopy; thermophoresis; fluorescence microscopy; Ca2+/Mg2+ imaging; apoptosis; necrosis; oxidative stress; nitric oxide; nitrosylation; glutathionylation; ER; mitochondria; cell physiology; heart disease; cancer; immunodeficiency

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Database Entries

Protein Data Bank (PDB)

Biological Magnetic Resonance Bank (BMRB)

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Personnel

Current

Qi-Tong (Tom) Lin - PhD candidate

Sukanthathulse (Tulsy) Uthayabalan - PhD candidate

Petra Samardzija - PhD candidate (joint-supervisor)

Danielle Colussi - PhD candidate

Zoya Lehman - MSc candidate

Nicholas Lukas - MSc candidate

Gary Zhu - Scholar's Elective student

Taylor Lake - Laboratory Technician

Alumni (year graduated) [next position]

Arine Pawakian - MSc graduate (2024) - [technician in UWO BioCore facility]
Hamza Guran - 4th Year Honour's Research Thesis Student (2024)
Arundhasa Chandrabalan - Post-doctoral fellow (2023) (joint-supervisor) - [Research Associate Sunnybrook Hospital]
Jaxen Smith - 4th Year Hounour's Research Thesis Student (2023) - [graduate school (MSc)]
Tian Yi (Tiffany) Zhao - Work Study student (2023) - [medical school]
Drake Christie - 4th Year Honour's Research Thesis Student (2022) - [graduate school (MSc)]
Megan Noble - MSc graduate (2021) - [medical school]
Christian Sirko - MSc graduate (2021) - [Science Research Analyst for investment company]
Sofya Ulanova - Work Study student (2021) - [graduate school (MSc)]
Shang (Selina) Shi - 4th Year Hounour's Research Thesis Student (2021) - [graduate school (MSc)]
Brian Bursic - 4th Year Honour's Research Thesis Student (2020) - [graduate school (MSc)]
Winny Wang - Work Study student (2020) - [graduate school (MSc)]
Sherry Wang - Work Study student (2020) - [dental school]
Jacob Houpt - Summer Research Training Program student (2020) - [medical school]
Melissa Fenech - PhD graduate (2019) (co-supervisor) - [medical school]
Matthew Joseph Novello - MSc graduate (2019) - [dental school]
Haley Jamison - 4th Year Honour’s Research Thesis Student (2019) - [medical school]
Naveed Siddiqui - MSc graduate (2018) - [Researcher Pfizer]
Steven Chung - MSc graduate (2018) - [Lab Manager SickKids Hospital]
MengQi Zhang - NSERC Summer Research Student (2018) - [medical school]
Vickie Yu Hsin Hung - 4th Year Honour’s Research Thesis Student (2018) - [dental school]
Rachel Lee - 4th Year Honour’s Research Thesis Student (2018) - [medical school]
Ryan Park - 4th Year Work Study Student (2018)
Shilpa Kumar - 4th Year Work Study Student (2018)
Allen Feng - 4th Year Honour’s Research Thesis Student (2017) - [dental school]
Jinhui (Gina) Zhu - MSc graduate (2017) - [dental school]
Benjamin Harvey - Laboratory Assistant (2016) - [graduate school (MSc)]
Yoo Jung (Lisa) Choi - MSc graduate (2016) - [medical school]
Samuel K. Lee - MSc graduate (2016) - [graduate school (PhD)]
Yue Zhao - Laboratory Assistant (2016) - [graduate school (MSc)]
Michael Kim - Summer Research Training Program student (2015) - [medical school]
Teresa Ching - 4th Year Honour’s Research Thesis Student (2016) - [optometry school]
Songyang (Sarah) Zhang – 4th Year Honour’s Research Thesis Student (2015) - [medical school]
Jamie Ching - Laboratory Assistant (2014) - [graduate school (MSc)]

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Funding

  • Canadian Institutes of Health Research
  • Natural Sciences and Engineering Research Council of Canada
  • Canadian Foundation for Innovation
  • Ontario Research Fund
  • Ride For Dad - Prostate Cancer Fight Foundation
Canadian Institutes of Health Research Natural Sciences and Engineering Research Council of Canada Canadian Foundation for Innovation Ontario Research Fund Ride For Dad - Prostate Canada Fight Foundation
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Available Positions

We are always looking for highly motivated trainees at the PDF, PhD and MSc levels with an interest in structural biology, molecular pharmacology and cell biology. Trainees will gain multidisciplinary experience studying the molecular mechanisms underlying Ca2+ and Mg2+ signaling in health and the bases for dysfunction in cancer and heart disease by integrating solution nuclear magnetic resonance spectroscopy and/or X-ray crystallography, computational biology, optical spectroscopies and other biophysical approaches as well as various live mammalian cell culture analyses.

If you are interested in this type of research and any of these positions, please contact Dr. Peter Stathopulos.

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Contact

Peter B. Stathopulos, MSc, PhD
Department of Physiology and Pharmacology
Schulich School of Medicine and Dentistry
The University of Western Ontario
Medical Sciences Building, Rm 232 (office) or Rm 219 (laboratory)
1151 Richmond Street, London, Ontario, Canada, N6A 5C1
Email: pstatho@uwo.ca
Phone: +1 (519) 661-2111 x83238 (office) or x82812 (laboratory)

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