Welcome to Medical Cell BioPhysics

Introduction

Medical needs for cell based diagnostics and treatments are increasing rapidly. Characterization of cells is becoming an integral part of disease diagnosis and therapy management. As a result the need for more sensitive and specific yet simpler and faster cell enumeration and characterization technology is needed. Multidisciplinary research covering cell and molecular biology, bio- physics and chemistry, nanotechnology, engineering and medicine are utilized to arrive at innovations that can advance disease management.

The figure depicts an artistic impression of the tools essential in practicing science. First we investigate the problem “Look”, then we figure out how to tackle it “Think” followed by the execution of our plan “Do”.

Kijken, Denken Doen watercolor by Guus Terstappen, the Eye to Look, the Brain to Think and the hand to Do.

Research

The focus of our research is to improve the understanding of cancer biology and develop technology that can improve the diagnosis and treatment of cancer. The developed technology can also be applied in other fields of medicine. For example a simple image cytometer has been developed for monitoring AIDS patients in developing countries.

Cancer is the second largest cause of death and is becoming a larger problem with the aging of the population. Death from cancer is mostly not caused by the loss of function from the site where the tumor arises but caused by dissemination of the disease and destruction of other organs. Cancer cells become dangerous when they break away from the primary site and settle elsewhere in the body. The cascade of events involved in the metastatic process is depicted in the figure. Tumor cells dissociate from their surroundings and penetrate through the blood vessel wall to enter into the blood circulation. The majority of tumor cells will be trapped in the capillary beds, die and are then removed by phagocytes.

Metastasis

Occasionally they will adapt to the environment and proliferate. A few tumor cells will penetrate the blood vessel wall to form a metastasis or to stay dormant for an undetermined period of time. Recurrence of cancer may arise after months, years or even decades, this indicates that microscopic disease must have remained present, at least in those patients that relapsed. Knowledge of whether and where “dormant” tumor cells are present and when, why and how they “awaken” is extremely limited.

We pioneered the development of technology that can detect the extremely rare tumor cells in blood of cancer patients. We demonstrated that presence of tumor cells in a tube of blood from patients with metastatic disease is associated with poor survival prospects. The Kaplan Meier Plot in the figure shows survival for metastatic prostate cancer patients. The lines show that patients who fall into the bad category after therapy do poorly irrespective of their category before therapy.

Kaplan-Meier Plot

People who fall into the good category after therapy do much better regardless of their category before therapy. This shows that treatment effectiveness can be measured an amazing two months earlier than conventional imaging techniques. Imagine what can be done for a patient in two months!

Next, the question arises which therapy can be effective. To that end our group is exploring means to assess the presence of treatment targets at the protein and gene level on tumor cells. Here, the technological challenge is to determine as many targets as possible on the same few cells.

Tumor cells can not only be detected in blood of patients with metastatic disease, but also in patients who are clinically free of disease, albeit at lower frequency. Cancer cells detected in blood of these patients clearly behave differently than the ones detected in patients with metastatic disease. Understanding the differences between these “killer” and “dormant” tumor cells may hold the key to our understanding of metastasis. The technology to detect disseminated tumor cells in a patient’s body and to examine their make-up needs to be improved for further exploration of this question. We may also need the development of in-vivo-cytometry technology. Proof of the presence of dormant tumor cells and understanding of the mechanisms involved in maintaining their dormancy status, will ultimately lead to controlling cancer.

The questions posed above lead to a variety of projects within our group. Some projects are with a larger emphasis on instrument development Other projects are on assay development. The rest of the projects are on algorithm development or on utilization of the developed tools and methods to answer biologic and clinically relevant questions. The ongoing Research Projects are described separately and each of them will have a variety of student projects to choose from. To help prospective students get a better feel of what to expect during their project, each open student project should have a diagram like the one shown in the figure. If you did not find what you are looking for visit us at our present location in the Carré CR4439.