Ursula Stochaj, PhD
Associate Professor of Physiology
Ursula Stochaj obtained a Diploma in Genetics from the University of Cologne
(Department of Biology) in Germany working on Escherichia coli lactose permease, a lactose/proton
symporter. For her PhD, she continued her studies on lactose permease and examined the biosynthesis
and membrane association of this carrier (University of Cologne). As “Hochschulassistent” she
studied transposable elements in maize (University of Cologne) and characterized the ectoenzyme
5'-nucleotidase and its interactions with the extracellular matrix (University of Marburg, Germany).
Ursula Stochaj subsequently trained as a postdoctoral fellow at Princeton and Harvard University,
where she analyzed the transport of macromolecules between the nucleus and cytoplasm. This work was
primarily carried out in the budding yeast Saccharomyces cerevisiae. Since 1994, she is a group
leader at McGill University in the Department of Physiology. In the past, her laboratory worked on
nucleocytoplasmic trafficking in yeast and mammalian cells and studied the impact of stress on nuclear
organization and function. Currently, the group examines the changes in nuclear homeostasis that are
caused by disease, stress or aging.
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At present, the laboratory works on several aspects of cell physiology that are essential under normal
and disease conditions. The emphasis is on cellular changes relevant to type 2 diabetes and cancer. To this end, we
concentrate on the cell nucleus and study the changes in nuclear organization and function that are caused by disease or
stress. Our research focuses on important factors that control nuclear homeostasis and thereby impact human health: 1) 5'-AMP
activated kinase, one of the targets of the anti-diabetic drug metformin, 2) molecular chaperones, and 3) nuclear components
that control aging. The laboratory uses a wide array of technologies in modern physiology, biochemistry, cell and molecular
biology. Our expertise in microscopy, imaging and quantitative image analysis, as well as the novel protocols we developed
in this field, are crucial to our research. We have also developed and performed high-throughput screens that measure drug-
and stress-induced changes in cell physiology. Our recent studies used gold nanoparticles to target nuclear parameters and
molecular chaperones in cancer cells.
5'-AMP activated kinase (AMPK). The serine/threonine protein kinase AMPK serves as an
energy sensor that is implicated in numerous biological processes. Due to its critical function in metabolism, AMPK is
recognized as a key player for many human diseases and disorders. As a regulator of glucose, lipid and protein homeostasis,
AMPK has become an important therapeutic target for type 2 diabetes, obesity and cancer. AMPK provides a focal point for
metabolic control in all eukaryotes, where it has essential functions in different organs and cell types. We examine how
AMPK regulates the nucleus and its activities. For example, we demonstrated that AMPK-activating compounds inhibit the
synthesis of RNA in nucleoli, which are the ribosome factories of the cell. This is important, because the production of
ribosomes is linked to diabetic complications, such as diabetic kidney hypertrophy.
Molecular chaperones. Molecular chaperones impinge on numerous aspects of human health.
Heat shock proteins and their co-factors in particular affect aging and a large number of diseases or pathologies. These
include diabetes, many types of cancer, as well as a growing number of protein folding and neurodegenerative diseases.
Members of the heat shock protein families participate in a multitude of processes that contribute to all aspects of cell
biology. As chaperones they are not only required for viability and growth under normal conditions, they also protect cells
from damage induced by disease-related or environmental insults. Our research focuses on members of the hsp70 family and
their co-chaperones. Using the protocols we developed for quantitative imaging in combination with other methods, it is our
aim to define how molecular chaperones control nuclear homeostasis.
Nuclear factors that control aging. Components of the nucleus play a critical role in
normal aging and premature aging diseases. To understand these processes at the molecular level, we concentrate on the
nucleolus and chaperones. Our experiments are carried out in kidney cells; more recently we have begun to examine the nuclear
aspects of aging in human mesenchymal stem cells.
Therapeutic use of gold nanoparticles. In collaboration with Dr Maysinger’s group at
McGill University, we use gold nanoparticles to modulate nuclear activities and the function of molecular chaperones.
These nanoparticles are particularly promising for diagnostics and therapeutic intervention in a large number of human
diseases, including cancer.