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Interview with Michael Nathanson on the occasion of his guest professorship

(Vienna, 15 October 2010) On 14 and 15 October, Univ. Prof. Dr. Michael H. Nathanson of the Yale University School of Medicine held two guest lectures at MedUni Vienna, which focused on the calcium signal pathways in liver cells and endoscopic imaging. Afterwards he gave a short interview about these topics.

Prof. Nathanson is one of the most renowned specialists in the field of liver diseases with a key focus on the signal pathways of calcium in liver cells and their pathogenic effects in case of changes. This was also the subject of the first guest lecture on 14 October, in which Nathanson discussed the impact of calcium signal pathways of liver growth and explained the possible effects on liver cell cancer and cholestasis (bile obstruction).

The topic of his second lecture on 15 October was Nathanson's second specialisation - endoscopic imaging. In this lecture he presented a new technique for confocal endomicroscopy, which will enable "virtual biopsies" for histological real-time diagnosis during the check. In the field of the liver and the gastrointestinal (GI) tract he presented both EUS- (endosonography/ultrasound) and ERCP- based procedures.

MedUni: If the calcium signaling pathway in the liver nucleus influences the cell growth (and so also cancer), do you think or have any evidence that this may be the same in other cells?

Nathanson: We do have some preliminary evidence that similar trafficking and signaling pathways exist in cells derived from other tissues, such as kidney, breast and ovary. Therefore we suspect that the signaling pathway we have described in the nucleus of hepatocytes is a general phenomenon that is widely applicable.

MedUni: The calcium signaling mechanism itself plays a main role by affecting enzymes and proteins, but also influences other functions within the human body. So, do you think it is a “global player” in humans health on which one should focus?

Nathanson: The short answer is yes. When you refer to calcium affecting other functions in the body, I presume you are referring to the well known role of calcium in bone formation, and the common health problem of osteoporosis. However, calcium plays several very different types of roles in human biology. Calcium is a critical second messenger in virtually every type of cell in the body, where concentrations that are several orders of magnitude lower than in the bloodstream are tightly regulated in order to control intracellular processes. But finally, we now realize that many cells also have an extracellular receptor that senses the concentration of calcium in the bloodstream and in the interstitial space, so calcium also can act similar to hormones as a first messenger for cell regulation.

Prof. Nathanson (left), Prof. Trauner (right)

MedUni: You are specialized on endomicroscopy too. How important is visualizing for diagnosis and therapy – like 7Tesla on our university - in your opinion, and what should happen in the near future to optimize this way of examination?

Nathanson: Endomicroscopy is a new frontier in diagnostic tools. 7 Tesla MRI scans can give cellular resolution of structures as small as 0.1 mm (100 microns) but confocal endomicroscopy can resolve structures as small as 1 micron. This is similar to what can be seen in tissue biopsies examined by light microscopy, but with these new imaging technologies this level of detail can now be seen in real time during the course of an endoscopic examination. Advances in endomicroscopy will likely depend on the ability to develop new fluorescent labels that can be used in patients, and may also depend on whether newer types of microscopy, such as multiphoton microscopy, which in certain ways is even more informative than confocal microscopy, can be adapted for use in an endoscope.

MedUni: Can you please explain the meaning of “virtual biopsies” on which your group is focused on – how would or is this affecting the clinical examinations and the patients?

Nathanson: A virtual biopsy is a histological image of tissue that looks like a real biopsy would look under the microscope, but the image is obtained of actual tissue in real time during the course of an endoscopic exam. This technique has the potential to permit true histological diagnoses to be made in real time during the course of an endoscopy. This technology could revolutionize the efficacy of endoscopic cancer screening procedures in gastrointestinal disorders such as ulcerative colitis or barrett’s esophagus, where we currently rely on random biopsies to search for evidence of premalignant changes such as dysplasia.

MedUni: Are you here at the MedUni Vienna for the first time or how is the collaboration between your university and ours?

Nathanson: Yes, this is my first visit to MedUni Vienna and in fact it is my first visit to Vienna. Your university was fortunate to recently recruit Michael Trauner as the new Chief of your Digestive Diseases Section, as he is one of the world’s leading investigators in liver disease. I have collaborated with Professor Trauner at various times over the years and I was quite pleased to accept his invitation to visit here and speak.

MedUni: What is your impression of the MedUni Vienna and what are the main differences between here and the Yale University School of Medicine?

Nathanson: I find the MedUni Vienna an extremely impressive complex, it is five times bigger than our university. Also you have a lot of various patients and an impressive research environment, this will give us a great opportunity for research partnerships.

Comment Univ. Prof. Dr. Michael Trauner:
I am very grateful that Professor Nathanson found the time to visit us despite his very tight time schedule. For us it is very important to have international exchanges and collaborations with top institutions such as Yale University since this will help us to achieve our goal of becoming one of the top medical institutions in Europe. We have heard two excellent talks which were  masterpieces of translational research and had a stimulating research seminar where our younger fellows and junior faculty could present their latest data and projects. I think this was very inspiring for our fellows and faculty, both in terms of scientific content and concepts, but also how to approach scientific and clinical problems.

Short biography:
Michael H. Nathanson, MD, PhD, Professor of Medicine and Cell Biology, born in 1955, started to study Mathematical Statistics in Berkeley in 1977 and then completed his Masters in Biomedical Engineering at the MIT and his PhD at Case Western Reserve University in Cleveland, where he also completed his medical studies in 1985.
His scientific career then led him to the Yale University School of Medicine, where he was assistant professor and became Director of the Center for Cell Imaging in 1994, since 2003 he has been Head of Gastroenterology and Hepatology and since 2009 also Head of the Yale Liver Center.
Nathanson has already received a large number of internationally renowned prizes and works for top-notch medical journals and various scientific societies. His extensive field of activities also covers numerous publications as well as seminars and guest lectures.