Cell Signaling

The research in my group is focused on understanding at a molecular level how signals are received by cell surface receptors and subsequently sent into the cell. The receptor we are focused on is called PDGFR and it is activated by the growth factor PDGF. Overactivity in receptors such as PDGFR has in many cases been shown to be associated with a multitude of disease states, including cancer. We apply various clinically used or experimental substances as well as genetic methods, to influence the function of PDGFR and study the cellular consequences of these manipulations. We investigate how these substances affect cancer development, focusing both on what happens in tumor tissue (cancer- together with stroma cells) but also within the individual cells. We have found that the activated PDGFR enters the cell and that there are different fates for the intracellular receptor; a part of PDGFR enters the cell nucleus where it affects gene expression, while another subpopulation of PDGFRs fragment into at least two parts that end up in different locations in the cell, where they may send out unique signals. We study these events with the goal of identifying approaches to selectively block tumor-inducing signals, with minor effects on other signals. Furthermore, there are a number of drugs in clinical use that inhibit the function of PDGFR but none of these are specific and also target large number of other proteins in the cell. One question we seek to answer is whether there is a therapeutic value in developing highly specific drugs against PDGFR signaling or if it is better to have drugs that affect many proteins at the same 

Papadopoulos N, Lennartsson J and Heldin CH. PDGFRβ translocates to the nucleus and regulates chromatin remodeling via TATA element modifying factor 1. J Cell Biol. 2018 May 7;217(5):1701-1717