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In January 2012, Laurie Glimcher (Figure ​(Figure1)1) will take a new position as the Dean of Weill Cornell Medical College in New York City. A celebrated immunologist who stresses the importance of interdisciplinary and collaborative science, Glimcher has contributed to the understanding of diverse fields from skeletal biology to metabolism. Glimcher recently spoke to the JCI about her science, her move, and her goals in the big city. Figure 1 Laurie Glimcher. JCI: You’ve spent most of your career in the Harvard system. Why is now the right time to move? Glimcher: It was the right job at the right time. If this had come up three or four years ago, I wouldn’t have even looked at it. But it struck me as an enormous opportunity. I could keep on doing exactly what I’m doing now, and I would still be very happy, but I felt that I should be thinking beyond my own lab at this point. I’m concerned about the future of academic medical centers in this country and the health of biomedical research, given the tremendous financial constraints that we’ve experienced in the last few years (and that I’m sure will continue) at the NIH. I wanted to play on a broader stage, really try to enable the science of others, and encourage the best translational research. I feel that requires bringing many different forces together — clinicians, basic scientists, philanthropists, pharma — anything that we can call on to facilitate the transfer of basic discoveries into the clinic. We should be able to do that, to use public-private partnerships to advance science and medicine, and I thought that given my background in biomedical science and my relationships to the private sector, I would be in a position to do that at Weill Cornell. JCI: Are you bringing your lab with you to New York? Glimcher: I am. It’s not going to be as big a lab as I have now, because I don’t think I can do everything, but I can’t imagine not continuing the research, because we have some really exciting projects at the moment. I’ll need to focus, to select the couple of areas I think are the most interesting. JCI: Your training was in immunology, but your research portfolio is quite diverse. How have your interests evolved during your career? Glimcher: I fell in love with immunology when I was a first year medical student at Harvard. I wanted to be a physician, but after internship and residency I went to the NIH, where I did a wonderful postdoc with Bill Paul. I’ve always sort of gone where the science has taken me, and a good example of that is the Xbp1 transcription factor that we cloned . . . following that pathway has led us into a lot of other systems, including lipid biology, diabetes, and now neurodegenerative disease. And then about six years ago, skeletal biology became a major interest in the lab. My dad is a skeletal biologist, so I guess I have the genes for it. We had dabbled in it before, but things really clicked when we knocked out a factor called Schnurri-3. We didn’t see the big blow-away immune phenotype when we deleted the gene that we expected. Then one day, the postdoc and the grad student working on the KO mouse came into my office, and I asked them what the bone marrow looked like. They said, “You know, we can’t really access it — for some reason the bone marrow seems filled in.” I suggested that they walk down to my father’s office at Children’s Hospital and take an X-ray of the mice. The mice had incredibly elevated bone density, and we then spent the next couple of years figuring out the mechanism by which that occurred. The work attracted a lot of interest from pharma, because osteoporosis is so common. We started a really wonderful collaboration with Merck, and I built a bone team that is now about half of my lab. The collaboration with Merck was more than just funding; our scientists worked with their scientists, and I think that could be a good model for that sort of partnership. JCI: Do you have a vision for what you’d like to create at Weill Cornell? Glimcher: Weill Cornell is in the perfect position for expansion because the current dean, Tony Gotto, and the board of overseers, chaired by Sandy Weill, have done such a wonderful job raising funds to build a new medical research building. That will allow us to recruit some really top-notch faculty to join the already excellent faculty there, and to forge ties with other institutions in New York City. Weill Cornell already has an outstanding clinical group, they have great medical students, and their biomedical research enterprise could very quickly become first rate. I hope to expand our clinical reach over the next few years to the medically under­served populations in New York. Also, medical education is very important to me. We need to figure out how to help medical students pay for medical school; I think too many of them end up in specialties that they wouldn’t necessarily have considered except that they have $200,000 in educational loans, so less lucrative specialties like primary care and pediatrics suffer. JCI: How does it feel to be the first female dean of Weill Cornell Medical School? Glimcher: It feels great. I’ve gotten so many e-mails from people offering their kind words. You know, I’m very interested in mentorship — I have been committed to it my entire career — and I admit that I have a special warm spot in my heart for women. I have worked very hard in my own group to make sure that the women have an equal playing field. I want to think a lot about that when I’m at Weill Cornell, about how we can emphasize diversity and really put our money where our mouth is to strengthen it.

On June 26, 2011, in San Diego, the Merrifield Award of the American Peptide Society was given to Richard DiMarchi of Indiana University. A day later, again in San Diego, the Outstanding Scientific Achievement Award of the American Diabetes Association was given to Matthias Tschop of the University of Cincinnati. Those attending both lectures might have witnessed many similarities; the Tschop and DiMarchi laboratories had been working as a single integrated unit across two universities for the last seven years, designing and optimizing new therapeutics for the treatment of diabetes and obesity (Figure ​(Figure1). 1). Figure 1 Richard DiMarchi (left) and Matthias Tschop. JCI: How did the two of you start collaborating? Tschop: We met at the Eli Lilly Research Laboratories, where Richard led drug discovery as a group vice president, while I was a postdoctoral fellow. Years later, when I had moved back to the US from Germany and Richard had left Lilly to be a chair of chemistry at Indiana University, we reconnected — our labs suddenly were just a two-hour drive apart. JCI: What avenue of research do you think has the greatest potential to improve the outlook for the obesity epidemic? Tschop: It seems increasingly clear that more than one neuroendocrine signal may have to be modulated at the same time in order to achieve beneficial metabolic effects with curative potential. Richard and I have been working on a series of approaches in which we are combining two or three gastrointestinal hormones into a single molecule. JCI: So are you both optimistic that we’ll find a drug-based cure for metabolic syndrome? DiMarchi: I am a perpetual optimist, supported by three decades of personal experiences. This kind of work requires steady progress made through contributions from many laboratories establishing a foundation for the discovery of transformative medicines. We believe that our work is contributing to the identification of a novel formula that might define a successful prescription for treatment. Tschop: More skeptical colleagues frequently point out to me that evolutionary pressures drove the development of redundant systems to efficiently ingest and store calories. My answer is always that reproduction is a pretty important requirement for the survival of the species too, but endocrinologists figured out how to interrupt it by tricking the brain into believing that there was already an ongoing pregnancy. We need to figure out how to trick the brain into believing that the stomach has been bypassed without actually cutting patients open. JCI: Your work at Lilly and now at Indiana University is largely based on macromolecules and, in particular, peptides — in spite of the limitation that peptide-based drugs almost always require injection. What are the advantages? DiMarchi: In many ways the peptides and proteins that have emerged as drugs are nature’s medicines. They have a high specificity of action with minimal off-target toxicity and natural routes of metabolic clearance. While injection is a limitation, the huge benefit is performance. However, it is important not to frame the question of drug discovery as an either/or option of conventional small molecules versus macromolecules. The combination of the two can deliver unprecedented efficacy with fewer adverse effects. JCI: Given that you moved from pharma to academe, you’re perhaps well positioned to answer the question of whether scientists will be successful in drug discovery outside of the pharmaceutical industry. DiMarchi: Large organizations may be required for cost-efficient drug development and production and marketing of drugs. However, it is individual scientists who deliver breakthrough discoveries. A laboratory composed of broadly trained chemists and pharmacologists can make a huge difference, if properly funded and appropriately nurtured. I am quite certain that Bruce Merrifield, the father of solid-phase chemical synthesis, could not have invented the concept if employed in a less supportive environment than an academic center like The Rockefeller University. JCI: You’re moving back to Germany this year. Will that be a challenge for your collaboration? Tschop: My wife and I are both from Munich, so when the Munich Hemholtz Centre together with the Technical University and the Ludwig Maximilians University Munich invited us to help build a new German Diabetes Center, it turned out to be an offer we couldn’t refuse. With our history of intense collaboration, Richard and I are both confident that the most fun is still ahead of us. And, Richard has a standing invitation for a sabbatical in the Bavarian Alps! JCI: How important have these collaborations been to shaping your science? Tschop: The most important lesson I have learned is that interdisciplinary and translational teamwork is — at least for us — key to every single breakthrough. It was painful at times, since we all speak different languages (literally and figuratively!) — but it always paid off.

Cells are able to sense the level of oxygen in their environment and can adapt by rapidly altering expression of various genes. This capacity has both positive and negative implications; following ischemic injury, it can help promote blood vessel growth and recovery, but in cancer, new vessel growth helps sustain developing and metastasizing tumors. In the 1990s, William Kaelin Jr. and Gregg Semenza (Figure ​(Figure1)1) revolutionized the understanding of cellular oxygen sensing by identifying many of the molecular players involved. Their continuing work in the field has led to the development of successful therapeutic strategies. In April, their contributions will be celebrated as they receive the 2012 ASCI/Stanley J. Korsmeyer Award. The JCI recently spoke to Kaelin and Semenza about their path to this prize.

Chronic myelogenous leukemia (CML) was the first cancer to be linked to a clearly defined genetic defect, a chromosomal translocation that generates a constitutively active tyrosine kinase. In the 1990s, Brian Druker and Charles Sawyers (Figure ​(Figure1)1) collaborated to develop the targeted therapies that transformed CML from a fatal disease to one that boasts a 90% cure rate. Their work has been widely recognized as revolutionizing the molecular treatment of cancer, and in April their contributions will be further celebrated as they receive the 2011 ASCI/Stanley J. Korsmeyer award. The JCI recently spoke to Druker and Sawyers about their research careers and this latest award.

On September 8, Johnson & Johnson awarded the 2010 Dr. Paul Janssen Award for Biomedical Research to Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases at the NIH, and Erik De Clercq, professor emeritus at the Rega Institute for Medical Research in Belgium (Figure ​(Figure1),1), in recognition of their work on HIV and AIDS. Named for physician and chemist Paul Janssen, known affectionately as Dr. Paul, the award honors active scientists who have made contributions to the improvement of human health. The JCI recently spoke to Fauci and De Clercq about the award, their careers, and the future of AIDS research.