The Kanarek Laboratory is interested in folate metabolism. It is surprising that this essential vitamin, so famous for its key role in development, hematopoiesis and cancer progression, is still a mystery when it comes to its cellular and whole-body sensing and homeostasis.
The Kanarek lab applies genetic perturbations, biochemical assays, molecular biology, functional genomic screens, and metabolite profiling by mass spectrometry in cell-culture systems and in vivo to study basic folate biology including folate metabolism, folate-related signal transduction, the oncogenic role of folate and folate homeostasis in normal physiology and pathological conditions.
In the Kanarek lab we study folate metabolism.
From cells to whole-organisms, in the context of normal physiology, cancer, and other pathologies.
We study the cellular response to folate deprivation and the systemic sensing and homeostasis of folate in mice.
Read more about why and how we study folate....
No cell, from prokaryotic to human, can survive without the essential vitamin folate (folic acid, vitamin B9).
Folate is an enzymatic cofactor vital for the biosynthesis of RNA and DNA and, therefore, required for gene expression and cell proliferation.
Folate deprivation is known to cause anemia and developmental defects.
Fast proliferating cells, such as embryonic, malignant, and immune cells, are particularly sensitive to folate depletion, and this has been translated into effective anti-folate therapy in cancer and autoimmune diseases.
However, albeit the essentiality of folate and its potential as a target for cancer therapy, we don't know much about the physiological response of cells or organisms to folate deprivation. The cellular response to low folate is unknown (see figure below), and how some cells survive folate deprivation better than others is still a mystery.... It is not clear if and how different organs play different roles in folate homeostasis at the whole-body level: Is there a regulatory system that oversees the systemic distribution of folate? Are folate levels sensed in mammals? If yes – where, and what is the molecular mechanism of folate sensing? How come some organs, such as blood cells, fetal tissues, and tumors, consume much folate and are sensitive to its deprivation, but it is the liver and kidney that contain high levels of folate even-though they don’t require much?
These are very basic questions that are key in our ability to prevent folate-deficiency related maladies, as well as to leverage the essentiality of folate for auto-immune and cancer therapies.