VOLUME 12, NUMBER 24 • JUNE 22, 2001Mentors Salute This Year's Graduates Following university tradition, the mentors of graduating students gave personalized tributes to the new Ph.D.s. Below are excerpts of this year's Convocation remarks.
Caroline Wan-Yin Ang Caroline Ang chose Rockefeller because it seemed a perfect place for a student with a background in molecular biology looking for interdisciplinary applications and because of its location in New York City. After considering work in molecular embryology, she settled into the Nottebohm laboratory, to study one of the most fascinating learned behaviors: vocal communication. One strategy to explore this complicated process is to study how the brain extracts the relevant information in language (or in the case of birds, song), memorizes that information and then imitates it appropriately. For her thesis, Caroline tackled one key element of this approach: understanding how nerve cells in the auditory pathway become selective for vocalizations. Further, she asked if this selectivity was plastic, that is, whether or not it changed with behavioral context. Caroline quickly learned one lesson from birds: to fly far and wide to gather what the situation demands. To move her project off the ground, she had to migrate to a laboratory on the West Coast to harvest various techniques and expertise. She also foraged locally, which is how we met. Serving as Caroline's co-advisor, along with Dr. Constance Scharff, who feathered this presentation, has been a wonderful opportunity. Not only have I discovered the marvels of the songbird system (my own work is in vision), but both Constance and I have had the wonderful experience of watching a bright, talented and determined student fledge the nest to develop an original research program. Caroline has taken up her migratory habits once more. This time she has fluttered all the way to Ireland with her new physicist husband Conor. From her latest perch she will be concerning herself with entities far larger than birds. She has accepted a position as scientific officer in biotechnology at Science Foundation Ireland to help expand the national scientific research program. And she is making up for the lack of New York couture by donning her Canadian Gortex for hikes with Conor in the beautiful countryside. Who knows, they might even stop to listen to a bird or two while roaming through the glens. --Judith Hirsch Aurel Betz
In the past year the public has been treated to the revelation that all the coding information in the DNA that comprises the "genes" in humans has been sequenced. Many headlines featured the "surprise" that we (humans) have "only" 30 to 40,000 loci in which genetic information is located compared to the 15,000 loci in fruit flies -- raising, among other things, the question of why are we so proud of ourselves. However, I think what failed to be said clearly enough in the news reports is that groups of interacting proteins are often required to perform a particular function, and this raises exponentially to very large numbers the functional number of possible protein clusters. So the public shouldn't get the idea that all problems have been solved or that we are simply twice as complex as flies. Now, in addition to this type of numerical nightmare, the community of people interested in transcription factors has discovered negative regulators of transcription factors, which change the concentration of specific active transcription factors. It was in this arena that Aurel Betz accomplished what we believe to be very important experiments. Aurel used fruit flies in his work -- possible only because of the generous time spent training him to do so by the students and postdoctoral fellows in Professor Mike Young's laboratory, a fine example of the possible collaboration open to the enterprising Rockefeller University graduate student. What Aurel proved, using molecular genetic techniques, is that the single representative present in flies of a potential negative regulator damped down the activity of the single Drosophila member of our favorite transcription factor family. Changes as small as two-fold in the number of active transcription factors had great consequences; for example, a two-fold increase in the frequency of a leukemia-like tumor, or during development an eye that was less than half normal size. These experiments led to powerful conclusions: 1) the putative negative regulator surely does have a negative effect in the animal and 2) relatively small changes in the level of a single active transcription factor can have drastic effects in the tissues of an animal. Aurel's time in our laboratory will total five years, but he had a two-and-a-half-year stint in another lab before he came to us. This is longer than the average time spent at RU. However, in my opinion, our graduate program definitely benefits from giving students time to find themselves and the scientific puzzle that is both challenging but ultimately soluble. --James Darnell Jr.
Grégoire Bonnet When Grégoire Bonnet moved from the Ecole Normale Supérieure in Paris to New York he was a young physicist. In a sense, he came to Rockefeller University to become a biology student. He was one of the first students of our new Center for Physics and Biology, surrounded by professors who were, themselves, learning biology. This scenario represents quite a leap of faith for a young man. His Ph.D. centered on the dynamics of single-stranded DNA breathing and folding to use for molecular recognition and computation. He studied self-hybridization, cross-hybridization, optimal sequence recognition and showed that these in fact reveal an optimal way to recognize a sequence. He also studied the thermal mode of double-stranded DNA. He then ended up, by using DNA as a "logic gate," showing the first step, a necessary step, for molecular computation. The work Grégoire has done is primarily experimental, but with a major theoretical and modeling component. This combination is a hallmark of Grégoire's talent, and also the capacity of students from the Ecole Normale. --Albert Libchaber
Yu Chen It was a different time a different place Beijing 1971 Mary and Clay Chen were blessed with Yu, their second son. Wanting their kids to have the best, They packed their things and headed west Where both sons wore a Tiger's vest. (As Arnie here can well attest, A Princeton B.A. beats all the rest.) To Yu, the complex was divine, Publishing papers like "Selective excitation of molecular eigenstates using state-dependent optical field design." Ideas were the food he preferred to dine. Pure academics would've suited him fine But he wanted an M.D. and became a student of mine.In the years he's been here at ole Rocky U He's published papers with ideas that are new. His approaches are novel, he's got his own view My ideas now seem stale; he's disproven a few. Yet he's high in my book with the respect that he's due. His work demonstrated his persistence To conquer tumor multidrug resistance But this dissertation was just one instance Of the many he pursued the full distance Each solved to his high standards of consistence While his work is impressive, I really should say It's helping out others that drives him each day Assisting any project that hit a delay Teaching kids from the high schools who can get in the way He always is patient and never says "nay." His heart is huge; he turns no one away. So to Ping, Qiao and Jenny, Chien, Mary and Clay, Yu Chen is a blessing. What more can I say? --Sanford Simon Julija Filipovska When Julija came to my lab, she chose to work on a rather complex problem -- involvement of RNA polymerase II in the replication of hepatitis delta virus (HDV) RNA. I remember suggesting to her that this project was indeed complicated and that she might want to consider one of the problems concerning mRNA splicing, which represents the main focus in my lab. Julija's reaction was very characteristic. She would not even listen to me. Once she made up her mind, she would not hesitate, and the HDV project was her final choice. In the end, both of us were partly correct: myself, in that the project was indeed rather complicated, and Julija, in that with her iron determination she would conquer any problem. With a lab in Japan, she showed that the only protein encoded by HDV, the so-called delta antigen, is in fact a transcription elongation factor. Looking back, I think that Julija's success was very much a direct result of her energy and determination. And what is particularly impressive is that she managed to achieve all that without missing a thing from the active cultural scene of New York. I don't think there was a single concert, movie or theater production in all these years that she did not see. On a more serious note, one thing that I perhaps understood the best about Julija was her deep emotional involvement in the difficult political events in her home country. Julija grew up in Macedonia and later studied at the University of Belgrade, and so it is only natural that the events of the past several years would affect her very strongly. For me it was a constant reminder of how fragile and precious is peace and stability -- and this peace and stability is what I would like to wish her from all my heart. --M.Magda Konarska Maarten Hoek Maarten is the latest representative of a line of Swarthmore graduates who have come to Rockefeller for their Ph.D.s, and distinguished themselves both here and in the hereafter. Before starting graduate school, he spent two years working as a research assistant in Fred Cross's lab at Rockefeller. Trypanosomes are the cause of African sleeping sickness, a disease that invariably kills infected humans and animals. Trypanosomes cover themselves with a series of protective surfaces that they change just often enough to evade our immune responses. They are very economical with this process and only express one surface type at a time. Maarten's project was to explore one hypothesis for how this process might be regulated. He showed great perseverance and success in pursuing this project during a period when we were still developing some of the techniques that he needed to do the necessary experiments in trypanosomes. It has been a pleasure for me and for his father, who is also a biochemist, to observe Maarten's development and increasing confidence as a scientist. Maarten would probably be voted "most valuable player" in the Cross lab. People in the lab must now survive and educate newcomers without using the most common advice from the past, which was "try asking Maarten." As a leaving present, we thought a cell phone would be as useful to us as to him, but he claims that there's a hole in the wireless coverage where he's working now! We were also delighted to share in the celebrations of Maarten's recent marriage. Maarten and Sarah were married by the same Dutch official who married his parents. By an amazing coincidence, his thesis was examined by the same external professor, Piet Borst, who had participated in his father's thesis examination, many years ago in Amsterdam! --George A.M. Cross Morgan Andrew Huse Morgan is one of a pair of identical twins, and I do hope it's Morgan who is here with us today -- Arnie Levine has a trick question he's going to ask, that only Morgan can answer, before he hands over the diploma. Many of us here know that protein kinases are crucial signaling switches that control whether the cell does one thing or the other. It is also well-known by most of us that a modification to the surface of protein kinases known as phosphorylation controls their activity and decides whether a kinase turns on an important pathway, or another one, or does nothing. Certain kinases, such as the transforming growth factor-beta receptor signal not by using just one phosphorylation site but as many five in this case. The difficulty for biochemists such as ourselves in studying such a protein that has so many phosphorylation sites is in making the signaling protein homogeneously. The kind of work I do in my lab, protein crystallography, doesn't train one to solve this problem. One of the great things about Morgan is that he first worked in our lab to determine the three-dimensional atomic structure of the kinase, the TGF-beta receptor kinase, and then realized that, in order to really understand it, he'd have to solve the problem of phosphorylation specificity. To do this, he moved to the lab of Tom Muir, and from Tom learned how to make peptides. In fact, it is well known to us that Tom refused permission to Morgan to work in his lab because Tom said that his lab was full. And one of the wonderful things about Morgan has been the way in which he insinuated himself into this lab so that, before Tom knew it, Tom was writing a paper for the Journal of the American Chemical Society describing Morgan's work. At the same time, Morgan has been working with Joan Massagué over at Memorial Sloan-Kettering. And that has been a most rewarding thing, and has resulted, finally, in the production of pure receptor protein that has specifically attached to it four phosphates at defined sites, made by a combination of the chemical synthesis pioneered by Tom Muir and by the cell biological work of Massagué. All this has changed the way we think about these proteins. Throughout his stay in my lab Morgan has demonstrated, despite a certain cheekiness, a keen insight into the essential questions underlying the questions he has worked on. And he's been extremely quick to follow the projects into the areas that capture the essence of the problem. He seems poised to begin a remarkable career as a scientist. --John Kuriyan
Martha J. Lewis It is a great pleasure for me to present Martha Lewis. Martha entered the Rockefeller M.D.-Ph.D. program in 1994 after graduating from Cornell, and it was a really fortunate day in my life just shortly thereafter that she came to see me to tell me about her interest in virology, infectious disease and her ambition to be a clinician-scientist. On that day and since, I have been incredibly taken with Martha's talent, her temperment, her ambition, her drive and her willingness to help others. She's also pretty good in the lab. Martha, on a serious note, is a very courageous and adventurous young woman. Shortly after beginning her project, I decided that I was going to leave Rockefeller and return to Ireland, to Dublin, to head a new department there. I had expected that Martha simply would fold the project and move along to another lab. On the contrary, Martha insisted that she was going to finish this project and further insisted that she was coming to Ireland with me. Over the next four years, Martha completed an excellent series of experiments and criss-crossed the Atlantic to complete her program and courses at Rockefeller. Not only did she finish an excellent series of studies with her usual style and panache, but I have to say that she played a central role in establishing my lab in Dublin really from scratch. Martha's studies were focused on a family of viruses known as the human T-cell leukemia virus, which were associated with rather rare but aggressive T-cell malignancies. She carried out a series of elegant molecular studies and was one of the first to crack one of the holy grails of HTLV research, in that she was able to establish a transgenic animal model mimicking the human disease simply with the expression of a single viral regulatory protein. Throughout her studies, Martha never lost her focus on pathogenesis. And I think this is an intrinsic part of the M.D.-Ph.D. program here, and also a great part of the tradition of clinical sciences at the Rockefeller. --William W. Hall
Daniel Lim Although he is the grandson of two chemists, Dan's initial interests were far from science. At an early age, he became an avid tennis player participating in national championships at the junior level. He then pursued a writing career, working as a newspaper journalist in high school and college. Only after obtaining a job washing glassware in Mike Botchan's lab at Berkeley, did he realized that his career was in science and medicine. Dan's extraordinary ability for independent work quickly emerged. Although he was working as a lab helper, to the surprise of his advisor and others at the Berkeley lab, Dan developed an independent research project, the results of which showed for the first time that a transcriptional repressor could directly inhibit DNA replication, a discovery that won him an undergraduate research award. To our great fortune, he came to New York to join the Tri-institutional M.D.-Ph.D. Program. After rotations with Fred Cross and Ulrike Gaul, Dan joined my laboratory, where he made a series of seminal discoveries. Dan could have written three theses and deserves three Ph.D.s. I'd like to describe just one of the extraordinary discoveries that Dan made while he was in my laboratory. Previous work in the lab had identified a large germinal layer in the adult brain where thousands of new nerve cells are born every day. It has since become evident that this reservoir of new nerve cells in the adult brain exists in all vertebrates studied, including humans. Dan's interest in medicine led him to ask: What is so special about this site? His work helped to identify the stem cells that give rise to the new nerve cells. As I said, this is only one of three discoveries Dan made during his tenure in the lab. With this devotion, many may wonder if Dan had any life away from the bench. Well, he did. His generosity has extended far into the community. Two years ago, he and his wife, who is a pediatrician, started the Millennium Kid's Foundation, a non-profit organization that raises money for school-based health clinics in Harlem. In addition, he mentored three high school students, one of whom became an Intel Science semifinalist this year. I greatly miss his presence in the lab, our lengthy, inspiring discussions late at night and, most of all, his generosity with everyone in the lab. --Arturo Alvarez-Buylla Sebastian Martinek Sebastian joined my laboratory in the winter of 1998. His entrance was unique. I had been at a meeting in Japan for two weeks. I left the lab for that trip with an unoccupied laboratory bench. Walking through the lab when I got back, this bench was now filled: gel boxes, pipettes, solutions, so forth, and there seemed to be an experiment under way. When I was a student I used to swipe bench space when a neighbor left for the weekend, but in this case there were notebooks, journals and paperwork stacked on the desk adjoining this bench, and then there was this new smiling face sitting in a chair at this desk. "Hi, Mike, I decided this is where I want to do my graduate work, I've gotten started after talking with some of the people here. Let me tell you about my project!" This was Sebastian Martinek. Sebastian designed a wonderful experiment. We had been looking for mutations in Drosophila that change the wake/sleep cycle. Genes we find in the fruit fly seem to play a role in the wake/sleep cycles of humans, so the fly helps us explore links between genes and our own behavior. But our list from Drosophila had stalled; it was seven genes long and wasn't getting any longer. Sebastian thought the problem might be that some genes affect other important biological processes so that mutations of those might not be recognized because the mutants were dying. Sebastian's solution to this problem was to selectively overexpress each of the fly's genes, one at a time, exclusively in that part of the adult brain controlling the wake/sleep cycle. He started by testing about 2000 of the animal's 13,000 genes. Seven new genes changed circadian behavior! You don't go looking for Sebastian around the lab these days. He has postdoctoral offers in California and up and down the East Coast, and he says he hasn't made up his mind yet. I think he likes to travel. To be fair, he does have a new interest. Partly due to his encounter with GSK-3 and collaborative work he has done with Arnie Levine's lab on Drosophila p53, he will probably go on to studies of genetics and cancer. --Michael Young Jorge Luis Muñoz Jordan It started with a phone call, in 1993. As he reminded me last week, Jorge was surprised that a Rockefeller professor would answer the phone himself. Jorge came to New York in 1992, to embark on a Master's degree at NYU. He called me because he wanted to do a lab-based Master's thesis, which was not an option at NYU, and he'd already studied trypanosomes in Venezuela. Once here, like students before him, he was seduced by the lifestyle of Rockefeller students, and he was admitted to our graduate program. African sleeping sickness is currently returning to levels seen at the start of the last century, but in relative terms it has been eclipsed by the decimation of Africa by HIV/AIDS. However, because they evolved very differently from more familiar organisms -- mammals, yeast, worms and flies -- trypanosomes have turned out to be interesting and relevant models for basic biological questions, as well as for the diseases they cause. The genes encoding different trypanosome surfaces are expressed from a special place in the chromosomes. They are at the chromosome ends, a location called a telomere. For some reason we're trying to figure out, trypanosomes apparently gain some advantage in using telomere proximity to regulate antigenic variation. By good fortune, trypanosome telomeres are similar to human telomeres in some respects, and we were fortunate to have a willing collaborator at Rockefeller, Titia de Lange, who is an expert on mammalian telomeres. Titia also discovered this role of trypanosome telomeres during her own thesis work. Jorge went to Titia's lab for six months and returned to mine two years later after being thoroughly telomerized. Like most students, Jorge has made many memorable contributions to life in the laboratory: in two laboratories in his case. It's been suggested to me that the most memorable moments may not be suitable for public revelation. Jorge sometimes amused us with his malapropisms but also surprised us with his insights into our own personalities. --George A.M. Cross Daniel Salo Reich Neuroscientists now realize that to understand the brain deeply, first we must understand the code with which cortical neurons talk to one another. Danny Reich was not intimidated by this unsolved challenge. With powerful theory and an elegant laboratory finesse, Danny has succeeded so well that his now-published thesis work tells us, for example, that a particular typical cortical neuron, talking to its colleagues in its native language, could communicate Lincoln's Gettysburg Address in the span of 10 minutes with 3,000 appropriately spaced nerve impulses. Danny is a true pioneer. While he was still an undergraduate at Yale, Danny volunteered and made his mark in our laboratory, including first-authorship of a little publication which brought some honor here. To our fortune, he declined splendid alternative M.D.-Ph.D. offers and came to Rockefeller. Danny has added color as well as wisdom to our environment. Two brief vignettes must suffice: Once in 1992, in curiosity I called the number of a peculiar-looking phone bill. I found myself talking to a presidential campaign headquarters. Though Danny was interacting science with us, he had taken a term off from Yale to learn some practical politics. What he does, Danny does very well indeed. Once in that same era, Danny handed me a pair of tickets and said, "You and your wife might enjoy hearing me play the fiddle." The tickets were to Carnegie Hall. The Yale University Orchestra was playing. Danny still plays the fiddle with our resident string quartet. --Bruce Knight Danny Reich's work combined technological advances at the bench with innovative mathematical approaches to attack one of the fundamental open issues in neuroscience: how neurons represent information. Continuing in the great tradition of Nobel laureate Keffer Hartline and other illustrious members of the Laboratory of Biophysics, including my mentors Floyd Ratliff, Bruce Knight and Robert Shapley, the goal of this work was not just to dazzle with its virtuoso display of multidisciplinary talent, though well it could. Rather, in Danny's hands, these studies, though highly quantitative in design and execution, yielded qualitative insights into how collections of neurons of the cerebral cortex work together to represent information. It is truly an honor to say these few words at Danny's graduation, but it is only a mitigated pleasure, since it is a reminder that we'll miss his daily infusions of insight and spirit. I look forward to the contributions of this brilliant student and scientist. --Jonathan Victor Andrei Solodsky The best way to present Andrei Solodsky is to explain briefly what question he answered in his thesis and how he went about it. After all, you only really know people by what they do! Our universe is full of mysteries. Finding answers to mysteries satisfies our inherent thirst for knowledge and benefits society. Remember Archimedes jumping out of his bathtub shouting "Eureka!"? Well, Andrei did not find the answer to his thesis topic in the bathtub. It wasn't that easy, but there are similarities! When one day, after several years of dedicated and hard work he finally had the answer to his mystery and walked into my office to share it with me, in his excitement he did look like he had just taken a bath! From his thesis title you wouldn't guess that Andrei addressed a key question about the birth of the universe. A high-energy collision between a proton and an antiproton at the Tevatron, Fermilab's powerful particle accelerator, is like an explosion creating, on average, about 100 particles of all kinds. In two dimensions, this firework-like spectacle looks like a beautiful pie. But in some collisions a large piece of the pie is missing! Who got it? Apparently, in these cases a piece of energy with vacuum quantum numbers escaped from, say, the proton and collided with the antiproton producing an asymmetric firework of particles. Such collisions are called "diffractive." The next question is whether the ingredients in the partially eaten pie are in the same proportion as in the full pie. In other words, does a collision with the vacuum produce the same variety of particles? In earlier studies, our group had found that this is indeed the case for particles made up of the ordinary up and down quarks. Andrei studied the production of J/Psi particles, which are made up of "charm" quarks, and found that this is true in this rather exotic case as well. In a pecan pie analogy, Andrei found that whoever ate the missing piece of the pie did not also eat the pecans from the rest of the pie! The vacuum is well behaved! Andrei did his work in collaboration with about 500 other physicists from 50 institutions. It took all these people several years to build a state-of-the-art particle detector, and five years to collect data of proton-antiproton collisions at Fermilab. But for Andrei, it was just as if all these people were working for him! He did the data analysis alone with dedication and high standards. He truly deserves the credit for this discovery. --Konstantin Goulianos Jelena A. Stewart There is one quality that describes Jelena better than any else: she thrives on complexity. She may not agree, but her family and friends have surely noticed that she likes to stir things up. She's always doing something contrary (this seems common to students from the University of Belgrade). Take graduate school, for example. Most students think it's tough enough as it is, but Jelena thought, wouldn't it be more fun to throw a baby into the mix? I wouldn't have the guts, but she did! And here she is today, having done a smashing job with both her Ph.D. research and Katerina, her baby daughter. This desire for all things complex is evident in her choice of research projects. I'll give you one example. In Mike O'Donnell's lab we try to figure out how proteins responsible for DNA replication work. These include the DNA polymerase and its numerous accessory proteins. The most dramatic enhancement of polymerase activity is by a ring-shaped protein dimer that encircles duplex DNA and tethers the polymerase on DNA during synthesis. Many of us have investigated the mechanism of how this dimer is assembled around DNA, and Jelena decided to break open the ring and study one monomer in great detail. This was not an obvious approach, since half a ring doesn't work, but her perseverance revealed that while the dimer alone forms a stable ring, when a clamp loader binds it, an open ring form is energetically favorable. This allows the ring to be placed around DNA. These insights also propelled crystallographic studies, and now a co-crystal of the monomer and clamp loader has been solved in John Kuriyan's laboratory. Her deep interest in this obscure monomeric form, when no one else was paying attention, significantly advanced our understanding of one of the most critical processes in DNA replication. Jelena also investigated many other mysteries of DNA replication, and her discoveries will provide research fodder for many curious graduate students to come. So Jelena, we hope you'll continue to be very very contrary in the future, as it works so well for you. --Manju Hingorani Yu Wong Wong Yu grew in Houston, Texas, in a science family. His father is a chemist, but his dream is to be a basketball player. It's not clear he ever gave up on his dream, but at least decided to postpone it. Wong came to the M.D.-Ph.D. program from the University of Chicago, where he studied chemistry. He took a detour to study Chinese language and then joined my lab at a time when we were trying to understand how recombinase-activating genes are regulated. He took an unusual step of trying a new technique using bacterial artificial chromosomes, something developed by Nat Heintz and Peter Model. He used the new technology to discover that the RAG genes are coordinately regulated by a mechanism that involves the simultaneous activation of two convergently transcribed genes by a single distal element. His work also had important physiologic implications in understanding the assembly of antigen receptor genes and maintenance of tolerance in the antibody system. This was a difficult and competitive project, and Wong worked very hard on it, and he was rewarded with publications in Nature, Science, and the Journal of Experimental Medicine. It was a real pleasure for me to work with Wong. He brought a calm and intelligent approach to a very difficult problem. His colleagues in the lab miss Wong's scientific insight, his warm camaraderie and his commentaries on the latest kung fu movies and Sunday morning cartoons. --Michel Nussenzweig |
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