CeMM Landsteiner Lecture Series

Named in honor of Karl Landsteiner, the Viennese discoverer of blood groups, the CeMM Landsteiner Lecture is given annually since 2007. The speakers, carefully selected by the faculty at CeMM, are prominent scientists whose molecular research are deemed to have had a significant impact on medicine. The lecture aims at the wider scientific community as well as the general public and is held in the stunning 18th century frescoed festive hall of the Austrian Academy of Sciences, where once Haydn and Beethoven conducted premieres of their work.

Karl Landsteiner (1868–1943) was born in Vienna, Austria and earned his medical degree at the University of Vienna in 1891. He received the Nobel Prize in Physiology or Medicine for discovering “individual differences in human blood”, which was the title of his Nobel lecture, held on December 11th, 1930. In that lecture, he described the four different types of human blood, or blood groups, and discussed the therapeutic applications of this discovery. Today, it is easy to see the broad implications of his work within diverse fi elds of medicine and biology. In recognition of his achievements, Landsteiner’s portrait adorned the one thousand shilling banknote in Austria, up until the introduction of the Euro.

2016: Emmanuelle Charpentier

The revolution of CRISPR-Cas genome engineering: lessons learned from bacteria

Emmanuelle Charpentier, Director of the Max Planck Institute for Infection Biology in Berlin, held the 10th CeMM Landsteiner Lecture on May 6, 2016, in the festive hall of the Austrian Academy of Sciences, which was filled up to the last place. Her magnificent talk on the CRISPR technology delighted scientists and lay audience alike and was also broadcasted via live stream. In front of some four hundred people, she explained the molecular basis of this ingenious genetic tool and the story of its development. "A fast and easy tool was needed - and that's was CRISPR brought. The CRISPR-Cas technology allows precise gene surgery in any cell and organism" – with those almost casual sounding phrases, Emmanuelle Charpentier summed up her discovery which has revolutionized biomedical research within only a few years and will have a fundamental impact on the future of medicine.

Deriving from bacterial defense systems against viral attacks, the CRISPR machinery can be transferred in virtually any kind of cell and organism. With an exchangeable piece of RNA, it is directed to a precise location in the genome where it performs a desired alteration of the DNA sequence. Thanks to the precision and efficiency of this technology, applications like gene therapy will become feasible and safe, providing new treatment perspectives for a broad range of diseases. Introduced by Anton Zeilinger, President of the Academy, and Giulio Superti-Furga, CeMM Director and initiator of the CeMM Landsteiner Lecture Series, Emmanuelle Charpentier’s talk was an extraordinary event in the baroque hall of the Academy. With the musical framework provided by the ensemble “Karat-Apart” and the subsequent cocktail reception, the 10th CeMM Landsteiner Lecture was in every aspect a memorable and joyful jubilee. Emmanuelle Charpentier’s energetic personality, as well as her unswerving dedication to science left an unforgettable and remaining impression to all of us.

 

2015: Laurie H. Glimcher

Stressed Out: A Novel Approach to Cancer Immunotherapy

The 9th CeMM Landsteiner Lecture was delivered by Laurie H. Glimcher, Dean of Weill Cornell Medical College in New York focusing on the disease of the 21st century: cancer and a novel idea to treat it. On April 27th, 2015 some 300 guests followed her lively and fascinating talk, where she presented a novel approach to cancer immunotherapy which looks promising to treat solid, very aggressive, and unfortunately often late diagnosed tumors like breast and ovarian cancer. These vicious tumors very often find creative ways to survive under various stress conditions including hypoxia, nutrient deprivation and chemotherapy. In her talk, Laurie H. Glimcher presented new findings on how these tumors can get stressed out and defeated by the immune system.

One could think of two strategies to achieve that goal: either to target the tumor directly, or to activate the immune system to recognize tumor cells as foreign and initiate a robust anti-tumor response. Both approaches can be accomplished by directly targeting a transcription factor called X-Box binding protein 1 (XBP1) that tumors utilize towards their benefit. Laurie H. Glimcher presented XBP1 as a novel very promising target for cancer immunotherapy which is especially relevant for treating aggressive solid tumors via two anti-cancer mechanisms: preventing tumor growth and/or activating the immune system to kill tumor cells.

2014: David M. Sabatini

Grow-Shrink, Get Fat-Stay Lean, Divide-Rest: How Cells Decide

The 5th of May 2014 marked the eighth CeMM Landsteiner lecture, which was presented by the American cell biologist and biochemist, David M. Sabatini, Professor at the Whitehead Institute and the Massachusetts Institute of Technology in Boston. His research focuses on the fundamental question of how cells grow. Amongst his most significant research contributions is the discovery and study of a protein which is now known to play an important role in our understanding of cancer and diabetes. In 1994, while still a graduate student at John Hopkins Medical School, Professor Sabatini discovered the protein mTOR which plays an important role in controlling growth in many species.

In the years since, he has focused his research on improving the understanding of mTOR and its functionality, making further surprising discoveries, including how mTOR also plays a role in diseases such as cancer and diabetes, as well as in the aging process. In giving the 2014 CeMM Landsteiner Lecture, entitled “Grow – Shrink, Get Fat – Stay Lean, Divide – Rest: How Cells Decide”, Prof. Sabatini outlined the fundamental, intriguing processes surrounding the mTOR protein that cells use to integrate internal and environmental cues, such as nutrient availability, to rationalize cellular decision-making such as proliferation or differentiation.

The lecture sparked a tremendous amount of interest as evidenced by the lively podium discussion that followed. In keeping with what is now the tradition, the lecture was preceded by a short concert, and followed by a cocktail reception. The concert was given by the Viennese scientist Gustav Ammerer, biotech pioneer and research group leader at the Max F. Perutz Laboratories (MFPL) of the University of Vienna. The accomplished amateur cello player provided an exceptional and most enjoyable start to the evening with his interpretations of Johann Sebastian Bach’s Suite No.1 in G major (BWV 1007), Allemande & Sarabande, and was also kind enough to play during the cocktail reception to enhance what was a memorable end to a splendid event.

2013: Hans Clevers

Stem Cells of the Bowel: Bright Site, Dark Site

The seventh CeMM Landsteiner lecture was presented by Hans Clevers of the Hubrecht Institute in The Netherlands, and President of the Royal Netherlands Academy of Sciences. Hans Clevers’ research has made fundamental breakthroughs in a number of different fields over the course of his career, and his most recent topic, stem cell biology, is no exception. His lecture, entitled “Stem Cells of the Bowel: Bright Side, Dark Side”, was presented to a mixed audience from all scientific disciplines alongside other interested parties on the 6th May, 2013.

Using entertaining animations peppered with little known historical insights, Hans Clevers presented the results of several projects performed in his laboratory over the last ten years, all centered around the dynamic lives of intestinal stem cells. He explained that the epithelial cell layer, which lines the 12 meters of the small intestine and helps us digest food, is exposed to one of the most violent biological environments on the planet, i.e. the contents of the gut. As such these cells don’t survive very long, and the entire lining of the gut needs to be replaced every four days. This massive cell turnover is made possible by intestinal stem cells, which ensure the continuous supply of new epithelium.

Hans Clevers explained how work done by his group led to the breakthrough discovery of the identity of the elusive intestinal stem cell in mice and the cultivation of artificial three-dimensional “mini” guts. Being able to grow healthy, functional tissue in the laboratory could revolutionize regenerative medicine and the ability to cure patients with intestinal and liver damage. The system will also give scientists a much- needed boost to better model and thereby study associated diseases such as colon cancer, in vitro.

2012: Ruslan M. Medzhitov

Host Defense Strategies

On May 3rd 2012, the sixth CeMM Landsteiner Lecture, was held by Ruslan M. Medzhitov of the Howard Hughes Medical Institute at Yale University School of Medicine, who is a pioneer in the field of innate immunity. He has been working on the intricacies of the molecular mechanisms of innate immune recognition and the control of adaptive immune responses for more than 20 years. “How does an organism distinguish self from non-self?” was the central question of his lecture.

Being able to distinguish between the body’s own cells and foreign pathogens such as bacteria and viruses is critical for the immune system to function effectively. In his talk, Ruslan Medzhitov outlined the three strategies that humans and other organisms deploy in order to deal with foreign invaders: avoidance, to reduce exposure to a pathogen; resistance, to reduce the pathogen burden; and tolerance, to reduce a pathogen’s negative effects.

The main focus of the talk was to convey to the audience that understanding tolerance to a pathogen is a crucial parameter in immunology. Analyzing virulence from an evolutionary point of view, reciting examples such as the Spanish flu of 1918, as well as describing novel experimental approaches, Ruslan created an intense public engagement that continued in the reception that followed. Jussuv Karajev (violin) and Marija Köhler (piano) provided the wonderful music that framed the event and managed to transport us to the majestic world of the Silk Road with dances from central Asia.

2011: George Q. Daley

Stem Cells and Regenerative Medicine: Breakthroughs and Battles

George Q. Daley, a world-leader in the field of stem cells, haematology and oncology, was the speaker of the 5th CeMM Landsteiner Lecture on May 2nd, 2012. George Daley is Associate Professor of Biological Chemistry and Pediatrics at Harvard Medical School in Boston, USA. He studies stem cells of the blood to define the molecular basis of human leukemia and to gain insights into normal blood development.

Before the start of the talk there was an impressive and inspiring performance of Franz Liszt’s Hungarian Rhapsody no. 13 in A-minor by Prof. Jan G. Jiracek von Arnim. The introductory speech was given by Giulio Superti-Furga, and commemorated Karl Landsteiner as the person who embodies better than anybody what molecular medicine is. He made special mention of David Baltimore, George Daley’s PhD super visor, as a person who has been extremely influential to CeMM and its principles. Giulio reminded the audience that George Daley made the first ever demonstration of a human oncogene causing cancer in mice and was the inaugural winner of the NIH Director’s Pioneer Award for highly innovative research.

In his lecture, George Daley stressed the importance of stem cell research, explaining that for some diseases animal models do not suffice. As an example, he mentioned Fanconi’s anaemia, a genetic disease of autosomal recessive type for which animal models do not phenocopy the human disease, which necessitates the use of human stem cells. But George Daley also raised awareness in the audience concerning the dangers of a rush to commercialization of early stem cell research, as there have been many cases of companies magnifying the benefits and trivializing the risks of stem cell treatment.

Moving on to research practices, Daley revealed himself as a strong advocate of a slow, step-wise and prudent approach to stem cell research. According to him, the participation of the public in the dialogue on stem cell research is imperative. When asked about the tumorigenicity of stem cells, he advised society to be patient: The first cell replacement therapy will be available soon, but this will most likely not occur in the anatomically complex tissues like heart, brain or lung.

2010 Helen Hobbs

Genes versus Fast Food: Eat, Drink and be Wary

Helen Hobbs, geneticist at University of Texas Southwestern and Director of the McDermott Center for Human Growth and Development, delivered the 4th CeMM Landsteiner Lecture entitled: “Genes Versus Fast Food: Eat Drink and Be Wary”. Her main research interest is the genetics of lipid metabolism and its link to obesity and associated human diseases such as atherosclerosis. Along with Ronald Victor and other investigators in Dallas she designed the Dallas Heart Study to identify ethnic differences in cardiac health. Over a period of 8 years, the scientists performed over 3,500 measurements and interviews on around 5,000 Dallas residents to search for genetic variants linked to liver fat content. By comparing the fat levels in the liver to genetic markers in each individual they identified a correlation between fatty liver disease and sequence variations in a gene encoding for PNPLA-3.

The second part of her lecture focused on the contribution of genetic variation to plasma cholesterol levels. In fact, there is a fifteen-fold increase in the incidence of coronary heart disease in the US as compared to rural China - Hobbs wanted to find out why. Using the individuals from the Dallas Heart Study, Hobbs and colleagues looked for mutations in the gene for a protein called PCSK9 that were associated with blood cholesterol levels. They found a loss-of-function mutation predominantly in African Americans that was associated with a 28% decrease in plasma LDL levels. The goal now is to use the knowledge about PCSK9 to develop new therapeutics to further reduce an individual’s risk of developing these progressive and chronic diseases. Her work has led to significant insight into the contribution of our genes to several severe human diseases, and as such makes her truly a pioneer in Molecular Medicine and a popular recipient of the 2010 Karl Landsteiner lectureship.

The musical framework of the lecture was brilliantly performed on the cello by Benedikt Hellsberg, the sixteen year old son of the current Chairman of the Vienna Philharmonic Orchestra, accompanied by Eva Ulrich on the piano. They played Robert Schumann, Fantasiestücke op. 73, and Camille Saint-Saëns “The Swan” from “Carnival of the Animals”.

2009: Vishva Dixit

Death Receptors, Ubiquitin Editing and Inflammasome Function

The 3rd CeMM Landsteiner Lecture was held on May 4th 2009 by Dr. Vishva Dixit, vice president of Physiological Chemistry at the biotechnology company Genentech in San Francisco. Genentech encourages the study of basic scientific research and is accredited as the founder of the entire biotechnology industry. Some of Vishva Dixit’s most notable scientific achievements are within the field of cell death, where he characterized the molecular components of the cell death receptor pathway and discovered new mechanistic paradigms for intracellular signaling cascades.

With his lecture, Vishva Dixit took the audience on a journey through his scientific discoveries. It began in the early 1990’s, when people seemed more interested in studying cell survival and growth rather than cell death. However, today cell death is known to be a critical process both for the early development of an organism as well as to maintain homeostasis during life. In parallel to the work on cell death, Dixit’s group also studied the molecular mechanisms of inflammation. Upon microbial infection, cells in the body respond very rapidly, which suggested the presence of an intracellular detection sensor to act as an alarm system. Along with other groups, they found that these sensor proteins also contained specific death domains that could recognize microbial components and induce the assembly of a large multiprotein complex known as the inflammosome, thereby activating the inflammatory response.

Vishva Dixit made the decision to work in industry because it gave him the opportunity to turn his scientific results on basic cellular mechanisms into therapeutic opportunities to impact the lives of patients. Indeed, his work on cell death is highly relevant for understanding the molecular mechanisms underlying cancer cell survival. This guiding principle, as well as the topics of his research, fit well with the mission of CeMM to use basic research to pursue innovative therapeutic approaches focused on cancer, inflammation and immune disorders, making him clearly a pioneer in molecular medicine as well as a highly suitable choice to present CeMM’s 2009 Karl Landsteiner Lecture.

2008: Kári Stefánsson

Genetics of Common Diseases in the Context of Human Diversity

Kári Stefánsson, Chairman and CEO of deCODE Genetics in Iceland, held the second CeMM Landsteiner Lecture on May 5th, 2008. The former Harvard Professor for Neurology, Neuropathology and Neuroscience presented the achievements of his company in developing products to improve the treatment, diagnosis and prevention of common diseases. It was one of the first commercial ventures designed not only to develop but also to directly reap the benefits of population-based genomics, which can be used to uncover genetic risk factors that predispose us to certain diseases, such as Alzheimer’s disease and diabetes.

Iceland, in fact, is the ideal place to embark on such an enterprise. The genealogical records of the population are very accurate, dating back to the ninth century, and Stefánsson can trace his own lineage back to a single Viking. With these valuable tools and his innovation and determination, Kári Stefánsson has managed to publish more scientific papers in a two-year period than any other biologist.

His company has discovered specific DNA sequences linked to a plethora of diseases, including prostate, breast and lung cancer, cardiovascular diseases and stroke. Stefánsson’s training as a neurologist also gave him an intense interest in neurological and psychiatric diseases. It has long been known that these diseases have a genetic basis, as they run in families, but identifying DNA sequences that confer an increased risk of developing them proved particularly challenging. Only recently, have Stefánsson and colleagues finally identified genetic risk factors associated with schizophrenia and autism, amongst a few others. Their hope is that within the next five years Health Systems will be using these risk factors to directly tackle disease prevention.

2007: John Kuriyan

Regulatory Mechanisms in Protein Tyrosine Kinase Signaling

John Kuriyan, Howard Hughes Investigator and Chancellor’s Professor of Biochemistry and Molecular Biology at the University of California, Berkley, was invited by Giulio Superti-Furga as the first speaker of this new annual lecture series, the “CeMM Landsteiner Lectures”, which was inaugurated on May 3rd, 2007. For 10 years there has been a close scientific collaboration between the groups of Superti-Furga and Kuriyan, which led to new discoveries on the mechanisms of enzyme activity in relation to cancer formation. His CeMM Landsteiner Lecture was entitled: “Regulatory Mechanisms in Protein Tyrosine Kinase Signaling”.

John Kuriyan is one of the most prominent and successful structural biologists in the world and has solved the molecular structure of many proteins associated with disease. His innovative work has given important insights into the most fundamental cellular processes, most notably mechanisms of signal transduction and DNA replication. Some of his other important discoveries were the first three-dimensional structure of the oncoprotein c-Src, and studies of Bcr-Abl, which causes specific forms of leukemia. Many of Kuriyan’s publications are considered to be milestones of molecular medicine.

Professor Kuriyan received his Bachelor of Science undergraduate degree in chemistry from the Juniata College in Pennsylvania, before attaining a doctorate at the renowned Massachusetts Institute of Technology in Cambridge with Gregory Petsko and with Martin Karplus at Harvard University. After 14 years at the Rockefeller University in New York, as Head of the department for molecular biophysics and Patrick E. and Beatrice M. Haggerty Professor, John Kuriyan moved to UC Berkley in s2002. He has published so far more than 140 scientific papers, a quarter of which can be found in the highest impact journals, including Nature and Cell. Many of the structures that were determined in his laboratory are prominent in all standard molecular and cell biology textbooks, which just goes to show how fundamental his discoveries have been and how far reaching his work will undoubtedly become.