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https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/bb86fd07-97c3-420c-9219-e21d46eda5b6/thumbnail_IMG_8789.jpg Systems, Synthetic, and Quantitative Biology The Systems, Synthetic, and Quantitative Biology PhD Program aims to explain how higher level properties of complex biological systems arise from the interactions among their parts. This field requires a fusion of concepts from many disciplines, including biology, computer science, applied mathematics, physics and engineering. Students with backgrounds in any of these disciplines are encouraged to apply. https://sysbio.med.harvard.edu/new-page-1 daily 0.75 2026-03-10 https://sysbio.med.harvard.edu/ying-lu daily 0.75 2024-09-12 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657112791412-1M7SN1QJBZHUUP5W04HQ/unsplash-image-Lw7BruqPnJY.jpg Ying Lu - Ying Lu Accuracy is a remarkable feature of a large number of biological processes. To maintain homeostasis, cellular protein degradation must be carried out with no less efficiency or precision than transcription and translation. My lab is trying to understand how the cell achieves accurate control of protein degradation and how its failure may lead to neurodegeneration and aging. Using modern enzymological techniques, namely single-molecule fluorescence/force spectroscopy and cryo-electron microscopy, we are investigating how the information in ubiquitin configurations is decoded by the proteasome, a universal protein machine in eukaryotic species, to command an accurate rate of protein degradation. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657112663218-N1FMQST71J2GDSLG6ONV/Systems+Biology+HMS-170-3.jpg Ying Lu - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/postdoc-funding daily 0.75 2022-08-06 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1658320831190-A8KAD449MFG5YJZZ287Q/unsplash-image-1PpyUZceg_I.jpg https://sysbio.med.harvard.edu/sean-megason daily 0.75 2026-03-10 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1671563027823-I18RY68W9FESE47NVBZX/unsplash-image-bwMhq_itmMU.jpg Sean Megason - Sean Tsung-Megason Our lab’s approach to doing systems biology in embryos is heavily based on imaging because of its unique ability to capture quantitative data at single cell resolution in living, functioning embryos. We use zebrafish because of their unique suitability for imaging, genetics, and genomics. We are developing a technology called “in toto imaging” that seeks to track all the cells in a developing tissue and extract quantitative, cell-based data through the use of fluorescent reporters. In toto imaging will allow us to determine complete lineages for organs and to extract cell-based frameworks for use in modeling. We are also developing a technology called FlipTraps. FlipTraps are a novel kind of gene trap with 2 important features: they generate endogenously expressed functional fluorescent fusion proteins, and they generate Cre conditional alleles. We are currently scaling up these efforts as part of the Digital Fish Project which aims to scan in protein expression and mutant phenotype systematically onto a cell-based armature and use these data to construct models that “compute” developmental processes. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657051550055-IZ8TQF0I009KRXGYU5N1/Systems+Biology+HMS-132.jpg Sean Megason - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/allon-klein daily 0.75 2025-12-11 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657112494604-SJGTYPDL2A33TY13AHVO/unsplash-image-COFXWa6LJdw.jpg Allon Klein - Allon Klein The Klein lab is fascinated by the question of how stem cells choose between alternative fates in developing and adult tissues... Today, one can strip differentiated cells of their fate by inducing pluripotency, yet it remains exceedingly difficult to target differentiating stem cells to a specific fate. His work focuses on germ layer specification in the South African claw-toed frog, Xenopus Laevis, which is a powerful system for studying cell fate choice and differentiation in a "native" biological context (rather than in cell culture). He is currently studying collective fluctuations of groups of genes, measured at the single-cell level, to test several possible hypotheses for how different fates are selected. Dr. Klein's research combines (1) traditional experimental methods used to study developmental perturbations, (2) novel assays for gene expression in hundreds of individual cells, (3) statistical tools for analyzing gene expression fluctuations, and (4) theoretical tools for characterizing stochastic cell fate decisions. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657112410244-H89Z169HSYY4TQ30WM65/Systems+Biology+HMS-179.jpg Allon Klein - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/community daily 0.75 2026-04-01 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1653677306910-L04F1JUGP5QT4WH3ZQXK/unsplash-image-MJqMxzsxLtM.jpg Community https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657820619888-0GQ3NKCSGVJP630J92Z8/friday+freeeze.png Community 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https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/820b1afd-f600-4225-989a-2b7f6b6a746e/photo+coming+soon.png Grad Student Profiles https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/3fcd6560-7e9d-46c2-a0d9-442b02a34cf7/EChen_MCO.jpeg Grad Student Profiles https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/fb56994c-4c01-44b4-bc7f-34b52bad82c4/headshot.jpg Grad Student Profiles https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/31b56457-395b-43a7-beee-50e0ee03d1ea/Liu.png Grad Student Profiles https://sysbio.med.harvard.edu/marc-kirschner daily 0.75 2022-07-24 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657112176028-U92DSMM0VDBXNZEVFHF6/unsplash-image-p1zy6izFI0M.jpg Marc Kirschner - Marc Kirschner Investigating biological organization in space and time. In the past, we have made significant contributions in three areas of fundamental biology: embryology, cell organization and cell cycle regulation. Each of these areas in different ways poses key questions regarding the coordination of biological events in space and time. A newer interest along the same lines is in cell size control. Our lab is unusually capable of developing quantitative, computational and theoretical methods that are applicable to a wide range of biological areas. This has given us an advantage in answering both old and new questions. Three areas are particularly interesting to us at the moment. Cell size. How do populations of cells maintain tight control over the variance in their cell size? We recently developed, or co-developed with collaborators, a number of new mathematical and biophysical methods for measuring cell size, and found clear evidence for size-dependent control of growth. We are now in an excellent position to identify the molecular mechanisms responsible for this. Ubiquitin-mediated degradation. Our lab discovered the Anaphase Promoting Complex, which is responsible for the controlled degradation of cyclin through the ubiquitin/proteasome system at a specific point in the cell cycle. We now know of ~1,000 genes that are involved in the control of protein degradation in humans, but the functions of these genes are almost completely unknown. Very few targets of ubiquitin ligases have been identified, and very few proteins that are known to be degraded through the ubiquitin/proteasome system have been mapped to their cognate ligase. Again we have developed several new methods for connecting ligases and substrates. We are particularly interested in transcription factor degradation. We are also developing methods for identifying the “degradome” of a cell, which in some serious sense is the flip side of the transcriptome. Gene expression and modulation of protein function in development. Although much is known about the conservation and variation in DNA and protein structure, the most important evolution happens at the level of developmental pathways and strategies. We have begun to look at comparative strategies of early development using transcriptomic time courses in Xenopus, sturgeon, and the hemichordate, Saccoglossus. We are keen to know whether these early programs are conserved or whether changes in early development presage later innovations and specializations. We now have an unprecedentedly powerful method for looking at transcription in single cells during developmental decisions. We are also working on new tools for studying changes in the proteome during development, in particular changes in post-translational modificatio https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1653999708929-SORSFAJLSJTC7XTAG7TR/marc+image.jpg Marc Kirschner - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/marcusbasanabout daily 0.75 2022-07-05 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657052169132-VG00JKPFPSICQUB0O8CV/basan+lab.jpg Marcus Basan - Markus Basan The complexity and heterogeneity of biological systems are formidable obstacles that must be overcome for achieving a more quantitative and predictive understanding of physiology and phenotypes on the cellular or organism scale. Such a level of understanding has remained largely elusive in biology, despite the extraordinary level of detail to which molecular interactions have been characterized over the past decades, as it often remains unclear how to harness detailed molecular knowledge to achieve this goal. In our lab, we try to tackle these challenges by identifying phenotypic patterns that can guide us in decoding the underlying molecular mechanisms and principles, which govern the behavior of complex biological systems. Our approach relies on the close coordination and mutual feedback between experimental and theoretical efforts and we combine careful characterization of physiology, genetic perturbations, omics technology and theoretical models. Fundamental biological questions that we are interested in include the role of metabolic strategies during growth and adaptation, tradeoffs between competing evolutionary objectives of microorganisms and how cells achieve homeostasis of cell size, cell number and cellular composition, as well as the breakdown of these mechanisms in disease. We use the well-characterized model organismsEscherichia coli and Drosophila melanogaster to address such questions. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657052076294-FC4BQE1O3GQKSHSPW9IX/markus+headshot.jpg Marcus Basan - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/postdoc-resources daily 0.75 2025-07-31 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1654004489871-XHE60ZFT7KTP9P1SAMNN/unsplash-image-nXt5HtLmlgE.jpg Postdoc Resources https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1654004698227-G4KFP65YDPF2FZP3NCWK/postdoc+as.png Postdoc Resources https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657829901758-MO9EC9NZ9OS2GNJ9R2AE/unsplash-image-lkA6qT_aGds.jpg Postdoc Resources https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657830908285-VGT7B8RKBB7M6RV8MN3O/unsplash-image-adCT4qOQeY4.jpg Postdoc Resources https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657049391727-XRTX266T6456SUP1F7W4/teamwork%2Band%2Bdreamwork.jpg Postdoc Resources https://sysbio.med.harvard.edu/graduate-student-resources daily 0.75 2022-07-25 https://sysbio.med.harvard.edu/galit-lahav daily 0.75 2024-05-22 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657051266803-TY8Y8U4IBOAX6TO9IZGK/Fig3_p53_spheroid_crop.jpg Galit Lahav - Galit Lahav Novartis Professor |Chair, Department of Systems Biology Our lab studies how individual cells translate internal and external signals into decisions such as growth, death, movement or differentiation. We quantitatively measure the changes in level, activity, or localization of proteins in single cells at high temporal resolution and correlate these behaviors with specific cellular fates. By visualizing how dynamical behaviors vary between different cells, we aim to tease out the reasons for varying behavior both in cell populations and in different cell types. Understanding these issues will be enormously important for understanding how drugs act on different cell types and organs, and for gaining insight into the reasons why different cells and people respond differently to specific drugs. We focus on the p53 signaling pathway. p53 is the protein most frequently inactivated in human cancer; more than half of all human cancers contain mutations in the p53 gene, and in almost all cancers the p53 regulatory circuit is functionally inactivated. Earlier work on p53 dynamics used techniques that average the behavior of millions of cells together (e.g. Western blots). We are interested in examining how individual cells behave. We use live single-cell imaging system and fluorescently labeled reporter proteins to determine how p53’s dynamic behavior is controlled, why different cells show different dynamical behaviors and what consequences these behaviors have on cell survival. We apply the same approaches and techniques to study additional networks in human cells such as the networks controlling DNA repair and cell growth. In the long term we are optimistic that these studies will help us predict how signaling networks in human cells will behave in response to new stimuli; how they can be modified or rebuilt to give a desired cellular output; and how to selectively increase the tendency for cancer cells to go in the direction of apoptosis by modulating the dynamics of the networks controlling this decision. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/7f86e037-326f-41aa-b34e-39b2366c3405/Galit_Lahav+V2+dept+site+05142024.jpg Galit Lahav - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/postdocoverview daily 0.75 2024-12-13 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1654003867383-NPPW5MBWLH5P64IZKZK9/unsplash-image-yhq2ymcPlZE.jpg Postdoctoral Overview - Postdoctoral Overview Postdocs at Systems Biology reflect the rich tapestry of the department and Boston in general. They come from all corners of the world and bring a variety of scientific backgrounds. Our postdocs go on to pursue a range of careers from tenure track positions at colleges and research universities to roles in consulting, drug discovery, editorial work, start-ups, and teaching. If you are interested in exploring the postdoctoral opportunities available at Systems Biology, please reach out to the PI/lab you are interested in working with and make sure to CC their administrative assistant. https://sysbio.med.harvard.edu/oyler-yaniv-lab daily 0.75 2022-07-27 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657562240608-PQZR3HGXQ20LOVI359DK/unsplash-image-_R7xhMy__c4.jpg Oyler Yaniv Lab - Oyler-Yaniv Lab How does the immune system maintain tissue integrity and function while clearing pathogens? The air we breathe is teeming with microbes and our skin and mucosal surfaces are home to trillions of bacteria. Our immune system must sift through this onslaught and respond to true threats in a manner that is tailored to the specific pathogen type and magnitude of infection. A weak or delayed response means the spread of infection, but over-reaction can lead to immune-driven tissue destruction and inflammatory disease. Shockingly, the immune system rarely fails. We are obsessed with understanding this fine balance and do so by exploring feedbacks between host and pathogen at the molecular, cellular, and whole organ scales. We believe quantitative questions call for quantitative solutions, so we blend methods and concepts from classical immunology and host-pathogen interactions, with biophysics, systems biology, and machine learning. We like to follow questions across multiple scales, often starting at the single cell level and ending at whole tissues, which we visualize using a variety of different microscopy techniques. We believe that the primary goal of conducting excellent research relies on training excellent scientists. The need for cross-disciplinary scientists with a deep understanding of infectious disease and advanced computational skills has never been more evident. We aim to create a diverse and inclusive space where trainees pioneer their own projects, have the freedom to explore ideas, and learn perseverance, accountability, teamwork, and professionalism. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657562152229-PZLC25GXA2U6SP9QHXSQ/Systems+Biology+HMS-081.jpg Oyler Yaniv Lab - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/debora-marks daily 0.75 2022-07-24 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657113092768-Z5AKS7CUSN5GS79HU7QX/debbie+marks+lab+main+faculty+page.png Debora Marks - Debora Marks One million human genomes, will it make a difference? The large and growing volume of genome information, from all forms of life, presents unprecedented opportunities for computational biologists. The challenge for our scientific generation is to turn an avalanche of sequence information into meaningful discovery of biological principles, predictive methods, or strategies for molecular manipulation for therapeutic and biofuel discovery. The Marks lab is a new interdisciplinary lab dedicated to developing rigorous computational approaches to critical challenges in biomedical research, particularly on the interpretation of genetic variation and its impact on basic science and clinical medicine. To address this we develop algorithmic approaches to biological data aimed at teasing out causality from correlative observations, an approach that has been surprisingly successful to date on notoriously hard problems. In particular, we developed methods adapted from statistical physics and graphical modeling to disentangle true contacts from observed evolutionary correlations of residues in protein sequences. Remarkably, these evolutionary couplings, identified from sequence alone, supplied enough information to fold a protein sequence into 3D. The software and methods we developed is available to the biological community on a public server that is quick and easy for non-experts to use. In this evolutionary approach to accurately we have predicted the 3D structure of hundreds of proteins and large pharmaceutically relevant membrane proteins. Many of these were previously of unknown structure and had no homology to known sequences; two of the large membrane proteins have now been experimentally validated. We have now applied this approach genome wide to determine the 3D structure of all protein interactions that have sufficient sequences and can demonstrate the evolutionary signature of alternative conformations. The vision for the Marks lab is to build computational methods that address three critical challenges (i) protein conformational plasticity in health and disease, (ii) genome-wide evaluation of mutations on disease likelihood, antibiotic resistance and personal drug response, and (iii) synthetic protein design. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1653999831120-546FKJCSRSL6OY3HF692/Debbie+Marks+headshot%282%29.jpg Debora Marks - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/michael-springer daily 0.75 2024-09-12 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657563453114-70PB1LZGBK8K58TPMIA5/unsplash-image-zz_3tCcrk7o.jpg Michael Springer - Michael Springer The Springer lab is interested in how evolution shapes and constrains how organisms respond to their environment. They analyze cellular responses in several related yeast species using a combination of in vivo fluorescence, synthetic and genetic approaches, and numerical and analytical modeling. Additionally, our research focuses on understanding the relationship between genotype and phenotype, with a special interest in how biochemistry, molecular design, and wiring can allow cells to process information from their environment and respond appropriately. By comparing similar pathways in related species and duplicated genes in the same species we can study the importance of quantitative features of pathways. Why have 10% of yeast genes been preserved in duplicate? By swapping the promoters and coding regions of a number of duplicate genes and monitoring both transcription and fitness we will determine which quantitative features of duplicate genes are required. Does over-expressing a protein increase the total protein abundance in a cell or decrease the expression of every other protein? How much can a protein level be varied before we observe phenotypic/fitness costs? How similar are environmental responses in related yeast species? How easy is it to evolve quantitative features of signaling pathways? Where does most of the functionally relevant evolution happen: mRNA abundance, protein level, post-translation modification, etc.? To address these and other related questions, we are focusing on cellular homeostasis, beginning with pH homeostasis. We mainly use fluorescence read-outs in response to the environment in different wild-type and mutant backgrounds to build quantitative data sets appropriate for numerical and analytical approaches. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657049821996-C0VD7Q7GC7D4XCKNBHIR/Systems+Biology+HMS-336.jpg Michael Springer - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/angela-depaceabout daily 0.75 2022-07-06 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657109774332-3ME32896T9SQAR8NX2OC/unsplash-image-J28Nn-CDbII.jpg Angela Depace - Angela DePace How do regulatory sequences control the patterns of gene expression? Whole genome sequence for a wide variety of organisms has shown us that across taxa, the set of protein coding genes is remarkably similar. How is this common genetic toolkit deployed in new configurations to generate organismal diversity? The evolutionary importance of changes in gene regulation during development is now clear, and a handful of examples have successfully traced the path from distinct phenotypes, to changes in gene expression, and finally to specific changes in genomic regulatory sequence. Yet we lack general principles describing how regulatory sequence relates to its output as gene expression patterns in space and time, severely limiting our understanding of how these sequences are functionally constrained during evolution. Gene expression in metazoans is controlled by the interaction among cis-regulatory elements (sometimes called enhancers), silencers, insulators, chromatin structure and core promoters. The vast majority of gene specific spatial and temporal information is contained in cis-regulatory elements, which are collections of binding sites for sequence specific DNA-binding transcription factors. Our current work is focused on two parallel questions. First, how do collections of transcription factor binding sites integrate information to produce gene expression patterns? And second, how do cis-regulatory elements and their associated expression patterns evolve? We focus on the early development of multiple Drosophila species, and integrate a wide variety of experimental and computational approaches. The early development of Drosophila melanogaster is directed by an extremely well characterized transcriptional network, giving us a large number of known transcription factors and regulatory elements to work with. Twelve Drosophila species have recently been sequenced, and more genomic resources are on the way. The relatively simple geometry of the early embryo has allowed us to develop quantitative imaging techniques that yield gene expression information for every cell in the entire embryo over time. Together, these resources give us the opportunity to bring a quantitative system-wide approach to evolutionary developmental biology. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1653587958535-8HRGEILLMLZYUT4R546S/depace.jpg Angela Depace - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/sahand-hormoz daily 0.75 2023-02-21 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657111688329-I6JQE62C9BFXYL1P2FX3/unsplash-image-6GynZ6MU-9E.jpg Sahand Hormoz - Sahand Hormoz Hormoz lab’s mission is to control biological systems to understand life and cure disease. We want to understand how different cell states emerge in diverse biological systems (viruses, bacteria, and mammalian cells) and use this knowledge to generate desired and even new cell states in a dish. For example, we try to generate blood stem cells from skin fibroblast cells and evolve viruses for gene therapy. To do so, we develop new technologies to measure the molecular states of single cells. These high throughput measurements create two challenges. First, the resulting data sets are high-dimensional and difficult to interpret. To understand the data, we use tools from differential geometry and machine learning. Second, high throughput measurements destroy the cells and provide only static snapshots. To obtain information about the dynamics, we use synthetic biology to engineer cells to record their histories in their own DNA. Finally, we develop organoid systems and microfluidic platforms to control cell states in vitro using the understanding obtained from the high throughput data. Ultimately, we aim to automate the process of measuring and modeling of biological systems so that our understanding and control of biology is not limited by human cognition. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657111628890-HI3UDW0PH2MXLOSZ0UMD/sahand%2Bhormoz.jpg Sahand Hormoz - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/ralph-weissleder daily 0.75 2022-07-27 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657567171251-0RWZQA9CAZA85H15VG3N/unsplash-image-4_hFxTsmaO4.jpg Ralph Weissleder - Ralph Weissleder The development of novel high resolution molecular imaging systems, tools for early disease detection, new and more advanced nanomaterials for imaging, and modeling methods for systems analysis. Increasingly, his work has been focused on reconciling the gap that exists between traditional cell biology and human biology. His work on imaging, nanomaterials and miniaturized chips has already led to a number of advanced clinical trials. When these techniques become routinely available, they are anticipated to have a major impact on clinical practice. Dr. Weissleder is currently the principal investigator of several National Institute of Health (NIH) grants and consortia. Projects My goal for the next 5 years is to explore, develop and apply fundamentally new approaches to cancer biology. It is my aim to 1) to develop novel, first-in-class imaging probes for key targets and pathways in cancer cells (“imaging major hubs and pathways”); 2) to use these probes to study clinically relevant tumor biology in vivo such as cellular heterogeneity of cancer and host cells (“imaging at single cell resolution”); and 3) to provide insight into therapeutic response and resistance at the cellular level (“single cell pharmacodynamics”). Some specific research projects include: Bioorthogonal small molecule in vivo imaging agents By harnessing a recently developed bioorthogonal in vivo detection (BIND) chemistry, which involves the highly specific and fast reaction between strained trans-cyclooctene and tetrazine derivatized imaging reporters, we are developing cell permeable small molecule affinity ligand-based probes that are capable of targeting key “hubs” in cancer cells. Current efforts focus on imaging PARP1, PLK1, HDAC, BCL-2, CTSE among others. These targets were selected based either on their unique importance to cancer proliferation or on their use as a measurement of therapeutic efficacy. In aim 1, we will develop and test a library of compounds for imaging at the microscopic level. For aim 2, we will focus on the protein-wide identification and validation of binding partners of lead compounds, for which we will use BIND-enriched stable isotope labeling with amino acids in cell culture (SILAC) to perform cell-based and in vivo proteomics. These experiments are critical since a comprehensive understanding of the interacting proteins and their associated protein complexes is important for the development of imaging agents and the interpretation of imaging studies. Finally, in aim 3 we will explore the translational potential of hits using the imaging probes determined from above. These will be investigated under combination therapy in genetically engineered mouse models. We expect that the BIND technology platform will have considerable translational potential for the imaging of a wide variety of intracellular cancer targets. Nanoscale real-time sensing using µNMR-chip technology There is a need for better detection platforms for specific mammalian cells, bacteria and viruses implicated in human disease. Traditional tools such as culture and biochemical analysis are often slow, rely on fixed (i.e. dead) tissue and require skilled personnel or specialized facilities. Recently, several rapid testing platforms have been developed that have the potential to provide rapid diagnosis in any clinical setting, but they are either insufficiently sensitive or require extensive sample preparation. Recent advances in nanotechnology and microfluidics now make this possible. We have developed a miniaturized nuclear magnetic resonance system (µNMR) that is simple and sensitive enough to be used in a clinical point-of-care device, and is well suited to profiling very low numbers of live mammalian cells or pathogens in complex clinical material. Several clinical trials are ongoing including : 1) detection of TB in sputum samples in Africa; 2) detection of circulating cancer cells in peripheral blood; 3) exosome profiling in glioma patients undergoing treatment; 4) profiling of freshly harvested human cancer cells to measure treatment response to novel drugs. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1654000407901-5UUSPKGIUQB029JGUY5V/ralph.jpg Ralph Weissleder - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/jeremy-gunawardena daily 0.75 2023-06-09 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657110994998-EZ5VFW2G3JVDTP4EK7XS/unsplash-image-Q3Hrvu9n3e8.jpg Jeremy Gunawardena - Jeremy Gunawardena Information processing in mammalian cells Signal transduction is the process by which signals impinging on a cell (for us, usually chemical signals) are converted into cellular behaviors, often initiated by programs of gene transcription. Historically, signalling has been thought of as some kind of pipe that conveys information from the outside of a cell to the inside, with the essential decision making taking place at the level of genetic regulatory networks. However, the molecular networks underlying signalling are extraordinarily complex, with enormous internal state, spatial and temporal localization, multi-protein complexes and interlinked positive and negative feedback loops. Instead of being just a pipe, it seems that signal transduction networks are undertaking complex information processing. How do we characterize this? Broadly speaking, we take two approaches. First, from the “inside out”, we study particular molecular mechanisms found in signalling networks. A major interest is in protein post-translational modification (PTM). Many signalling proteins are modified in multiple ways on multiple sites, leading to a potentially enormous range of combinatorial molecular states. We are developing biophysical methods (mass spectrometry and nuclear magnetic resonance spectroscopy) for accurately measuring these states, at least for proteins with small (< 10) numbers of sites [Prabhakaran et al. 2011]. We also use what we call “systems biochemistry” to understand how multiple forward and reverse enzymes collectively regulate the distribution of PTM states. The combinatorial complexity in PTM is a particular challenge for mathematical modelling. Simulations require parameters to be specified in advance, especially the number of modification sites, making it hard to see the biological wood for the molecular trees. We have been developing analytical methods for overcoming this, at least in the steady state, [Thomson and Gunawardena 2009a, 2009b; Manrai and Gunawardena, 2008]. These methods rise above the “parameter problem” and have proved to be widely applicable to cellular mechanisms other than PTM. The second approach is from the “outside in”. This arises from a different perspective, which suggests that the complexity found inside cellular networks cannot be fully explained by just studying the networks. Instead, the internal complexity reflects the external complexity of the environments in which those networks were evolved. We are developing new types of microfluidic devices to subject cells to complex external environments, using various forms of microscopy to assay their downstream behaviours at a single-cell level and exploiting mathematical models of the signalling networks to predict what we should see. We have developed flexible computational infrastructures (“little b” and, more recently, “Proteus”) to support this kind of modelling, [Mallavarapu et al. 2009]. Instead of studying networks by pulling them to pieces, as in the first approach, we try to ask them more complex questions, so that their answers are more informative about why they are wired up as they are. One of the most awkward problems in studying signalling is that each cell is an individual entity and may respond to a signal differently from its neighbours, even in a clonal population. This cell-to-cell variation is obscured by population averages like Western blots. We try and use the variation to glean more information about the networks but cell culture is such an artificial environment that the variation is hard to interpret biologically. We are now moving towards more physiological contexts, including embryonic stem cells. Signalling in eukaryotic cells is a fascinating area in which ideas from mathematics, physics and engineering are starting to provide new conceptual insights into biology. There are no shortage of hard questions for those who enjoy prospecting in unexplored territory. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1653588047774-JPMRZVNSO66O7E3M6NZX/jeremy.jpg Jeremy Gunawardena - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/walter-fontana daily 0.75 2022-07-06 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657110271016-XDLDWMEEAJC3G1Q9CKPW/walter+lab+image.jpg Walter Fontana - Walter Fontana Models as a way of reasoning about biology The challenge of systems biology is not only experimental in kind. It also is the challenge of reasoning about facts that are rapidly evolving while remaining highly fragmented across research communities. I see a fundamental role for models as reasoning instruments in biology. Models, not databases as we know them today, will become the main vehicles for the computer-assisted storage, communication, and retrieval of biological knowledge. Computer scientists and I have joined forces with several other researchers to design a computational environment that represents biological knowledge, as it pertains to signaling, in an editable and executable fashion. This instrument will lend itself to the collaborative construction and critique of models. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657110207079-32SJ4S0LFLV32DCUJDXP/Systems+Biology+HMS-026.jpg Walter Fontana - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/johan-paulsson daily 0.75 2023-01-06 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657562357703-K6Y0E5GBJ8I4KIO581UP/unsplash-image-Wk902ZLaA7M.jpg Johan Paulsson - Johan Paulsson Life in single cells is dictated by chance: reactions that involve small numbers of molecules generate spontaneous fluctuations that then enslave all dependent processes. Such ‘noise’ can randomize developmental pathways, disrupt cell cycle control or force metabolites away from their optimal levels. It can also be exploited when heterogeneity is advantageous, or even to obtain more reliable and deterministic control. The goal of the laboratory is to identify and understand the guiding principles behind these different phenomena. To this end we derive mathematical methods to interpret fluctuations, develop experimental methods to count molecules in single cells, and combine the two to study the simplest natural and engineered networks. Different applications may use different organisms, but E. coli is the first choice. The individual network analyses form three more comprehensive projects: 1) A study of basic dynamic differences between different motifs in replication, gene expression and metabolism. 2) A comparison of different evolutionary solutions to the same regulatory problem, exemplified by homeostatic noise suppression. 3) A thorough quantitative characterization of the perhaps most tractable life form on the planet, bacterial plasmid R1. This includes evaluating the molecular mechanisms behind replication control and DNA segregation in terms of precision, cost and selfishness/altruism. The mathematical projects also aim to build a more systematic stochastic theory for biochemical systems, approximating structural classes of random processes collectively and concretizing the interpretations rather than the assumptions. For more information, see my homepages in Applied Mathematics at Harvard or Cambridge. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1654000176177-GRYJLQUPXSYUKB7LDUCQ/johan.jpg Johan Paulsson - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/petersorgerabout daily 0.75 2022-07-27 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657563207479-K8Q9DHOSIJMYL0NQ6E9X/unsplash-image-LiNIONbajm4.jpg Peter Sorger - Peter Sorger Otto Krayer Professor of Systems Biology Peter’s research focuses on the systems biology of signal transduction networks controlling cell proliferation and death, the dysregulation of these networks in cancer and inflammatory diseases and the mechanisms of action of therapeutic drugs targeting signaling proteins. His group uses mathematical and experimental approaches to construct and test computational models of signaling in human and murine cells as a means to understand and eventually predict the responses of cells and tumors to drugs applied individually and in combination. The Sorger group also develops open-source software for analyzing biological networks and it participates in multiple collaborative programs working to improve data reproducibility. As head of the Laboratory of Systems Pharmacology (LSP) Peter leads a university-wide effort to advance the basic and translational science used to develop new medicines, identify responsive patients and evaluate new drugs via precision clinical trials. The LSP is a highly collaborative research environment involving faculty from eight different institutions. Peter supervises graduate students, postdoctoral fellows and research staff active in bench science, computational modeling, and clinical trials – cross functional research and traiing is the norm. Over 30 former students and fellows now hold faculty positions in the US, Europe, and Asia and a similar number individuals are leaders in the biotech, software, and pharma industries. If you are interested in joining the lab please contact Peter directly (copying Christina). https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1654000264392-EOMNN91KOFK3HMZEA435/sorger+lab.png Peter Sorger - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/peng-yin daily 0.75 2025-11-20 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657567379177-3949ZNLP6ZS1S9BEZFSD/unsplash-image-xzH7K6nVVgI.jpg Peng Yin - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1654632364342-0F7J2DJRTJA4TDY4NWU0/yin%2Blab.jpg Peng Yin - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/tim-mitchison daily 0.75 2024-09-12 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657560957696-174I29DYPF92W5P01YSC/unsplash-image-LnvCEXQwC-o.jpg Tim Mitchison - Tim Mitchison The Mitchison group has long been interested in fundamental mechanisms by which cells use for physically organization and movement. Our main focus is on dynamic organization of the microtubule cytoskeleton, in particular during cell division. We use eggs of the frog Xenopus laevis as a model to study this problem and also as an example of an extremely large cell, where the scaling gap between molecular and cellular processes becomes extreme. We analyze microtubule-based organizing mechanisms by microscopy, image analysis and biochemistry, often taking advantage of egg extracts that reconstitute complex processes ex vivo. In the pharmacology area we are working on how microtubule- and mitosis-targeting drugs kill cancer cells, in particular how the important anti-cancer drug taxol works to promote tumor regression in man. We are also developing small molecules that activate tumor-resident macrophages by mimicking viral infection, and cause an innate immune attack of the cancer. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657561195717-220RY4HNE65WKYN3CQGC/Tim.jpg Tim Mitchison - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/pam-silver daily 0.75 2024-09-12 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/58f30c26-fb88-490f-b6ab-dc8f608fef50/thumbnail_IMG_6790.jpg Pam Silver - Pamela Silver Elliot T. and Onie H. Adams Professor of Biochemistry and Systems Biology We seek to both enhance our understanding of natural biological design, and to develop tools and concepts for designing cells, tissues and organisms. In the long term, we hope to develop principles for building synthetic cells that act as sensors, memory devices, bio-computers, producers of high value commodities and energy from the sun, and to build novel subsystems such as proteins with designed properties for therapeutic use. Current projects use mammalian cells, simple eukaryotes and prokaryotes. Understanding how to program cells in a rational way will have value, for example, in stem cell design, drug therapy and the environment. These experiments use a combination of theoretical and experimental approaches that are well suited to students with backgrounds in biology, engineering, or any allied field. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657049798409-TQKTHEDIDXO9OE9VKWMZ/Systems+Biology+HMS-238-2.jpg Pam Silver - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/graduate-student-overview daily 0.75 2025-07-14 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1658513444273-WPC84VR7R6V1UZL85CE7/SSQB+students+chatting+at+poster+sessions.jpg Graduate Student Overview Graduate Student Overview Graduate Students at Systems Biology reflect the rich diversity of the department and Boston in general. They come from all corners of the world and bring a variety of undergraduate backgrounds. Our grad students go on to pursue a range of careers from positions at colleges and research universities to roles in consulting, drug discovery, editorial work, start-ups, and teaching. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1658513258528-TCB09PK0TAATULM805VC/unsplash-image-8s8SbqgMxoI.jpg Graduate Student Overview - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/john-higgins daily 0.75 2022-07-06 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657111090483-VEPHQ6ULQ4CGUQIDTJ2M/unsplash-image-gIaA5PyXgDY.jpg John Higgins - John Higgins Mathematical descriptions of human pathophysiology Pathophysiology may be described at the molecular, cellular, tissue, and organismal levels and may show clinically significant variation over time scales ranging from seconds to years. My research combines clinical and pathophysiologic insight with dynamical systems theory to pursue two goals: (1) advance fundamental understanding of the dynamics of human pathophysiology, and (2) improve patient diagnosis, monitoring, and treatment. https://sysbio.med.harvard.edu/department-retrea-past daily 0.75 2023-08-28 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/e87fc831-4d46-4bf7-b9f2-7ed4fd7b3353/Fontana+Lab+at+the+poster+session+night+2.jpg Department Retreats Past https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/62007a2e-980c-4c02-86ba-45d46da072dc/Rachel+and+Will+%28labops%29+serious+discussion.jpg Department Retreats Past Sysbio Lab Managers solving problems https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/f01eb2dd-b851-467e-a81e-408befba9b2c/poster+session+night+2+%28image2%29.jpg Department Retreats Past Describing the research https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/ac784dac-adeb-4512-adc9-a35abb24dbfe/Learning+about+science.jpg Department Retreats Past Poster Session Night 2 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/f7abe292-6a30-4aba-b9dd-0aae2ac375b6/Ying+lu+at+poster+session.jpg Department Retreats Past Poster Session Main Room Night 1 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/f3b21b46-1e5b-4d4f-b9a6-c69ae3bb026b/group+session+walter.JPG Department Retreats Past Walter Fontana talk at Retreat https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/cce88245-0b1f-4e55-93ec-1efdb3b4038f/06012022+Science+Talks+1+-+Mike+Springer1.jpg Department Retreats Past Crowd Shot https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/e3458589-3eb0-4f4a-bdc1-6124b4fe3b6c/006022022+Poster+Sessons+2.4b.jpg Department Retreats Past Group Photo on Poster Session (left to right - Sean Megason, Jennifer Waters, Jen Oyler-Yaniv, Alon Oyler-Yaniv, and Talley Lambert) https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/064e4c70-fdd6-4fc2-be7d-bcc10a02b264/poster+44.JPG Department Retreats Past Lab Members Chatting https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/5e07139b-6fd3-4b4d-9f34-02a69db6ad31/SSQB+grad+students+in+deep+discussion.jpg Department Retreats Past SSQB students deep in conversation https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/d50c966d-2ff1-46da-ad6d-da1b983afdca/Retreat+dinner+first+night.jpg Department Retreats Past Dinner time (for the win!) https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/e08da584-04e2-4f3b-8010-b623d4c3ca34/06022022+Dance+Party+1.6.jpg Department Retreats Past Dinner Time Conversations https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/4d06867e-959d-40db-bafc-4d043184acbe/06022022+Science+Talks+2+-+Peng+Yin1.jpg Department Retreats Past Peng Yin delivers his Science Talk at the Retreat https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1c4d695b-b5bf-462f-8a62-af30a69b8924/06012022+Science+Talks+1+-+Allon+Klein1.jpg Department Retreats Past Group wide shot at science talks https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/bb49337a-9a6b-410f-beba-2b5596d6d1fe/06022022+Science+Talks+2+-+Jen+Oyler-Yaniv1.jpg Department Retreats Past Jen Oyler-Yaniv Talk at Retreat https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1656018758864-DNNJSSJJRM4BS0OLQP5B/06022022%2BDance%2BParty%2B1.16.jpg Department Retreats Past Lahav Lab at Dinner https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/6b875b0f-91f4-490f-a635-ca1f0af53796/Poster+Session+night+one+at+the+bar.jpg Department Retreats Past Science never stops! Not even for last call https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/5ea8def7-c2eb-42b3-8387-8c24f9b732a7/poster+43.JPG Department Retreats Past Poster Session Discussions https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/e2739053-9bfc-47e0-a319-9826a6eca347/Tide+Pooling+4.jpg Department Retreats Past Tide Pooling Demonstration led by Labops Frog Facility Manager, Rachel Jonas-Closs https://sysbio.med.harvard.edu/vamsi-mootha daily 0.75 2022-07-11 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657561386328-ZTAKED5EUASFM81KBWMR/unsplash-image-2hQoqUG8qPQ.jpg Vamsi Mootha - Vamsi Mootha Our laboratory focuses on mitochondria, these tiny organelles found in virtually all human cells, serving as the center stage for energy metabolism, ion homeostasis, and apoptosis. Their composition, copy number, and efficiency are dynamic properties, varying across cell types and remodeling during growth and differentiation. Mitochondrial dysfunction underlies rare, inborn errors of metabolism, as well as some of the most common human diseases, such as diabetes, cancer, and neurodegeneration. Given their importance in basic biology and clinical medicine, mitochondria represent an excellent "model" for basic and clinical systems biology. Our group is broadly interested in characterizing the structure and dynamic properties of mitochondria, understanding how genetic variation influence mitochondrial physiology, and exploiting the network properties of the organelle to design therapies for human disease. To achieve these goals, we combine classic biochemistry and physiology with the new tools of genomics, proteomics, and chemical biology. In recent years, we have used mass spectrometry, microscopy, and computation to define the mitochondrial proteome (an inventory we call MitoCarta). We have subsequently coupled MitoCarta with human genetics to discover six Mendelian disease genes. We have used computational and comparative genomics in combination with RNAi screens to predict and validate the function of proteins involved in biosynthetic pathways as well as in calcium homeostasis. Current areas of focus include: (1) nuclear:mitochondrial cross-talk in the control of mitochondrial biogenesis, (2) membrane biochemistry and biophysics of ion and metabolite transport, (3) next-gen sequencing and functional studies of human mitochondrial disease, (4) metabolomics approaches to mitochondrial function, and (5) chemical biology approaches to modulating mitochondrial copy number and function. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1654000026399-I548VICB2AS0STXQ9MYM/vamsi.jpg Vamsi Mootha - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/about-our-faculty daily 0.75 2025-12-09 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1658171075935-T7IKB5X3KAUDANRTBCXT/unsplash-image-7EqQ1s3wIAI.jpg Faculty Overview https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1658240001029-UJ7EXJ7690OE9WSNO6RH/unsplash-image-RDEaV381Cxg.jpg Faculty Overview https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1658240041487-31DK5K7JAC348SA3C5UR/unsplash-image-MgntZq5RYa0.jpg Faculty Overview https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1658240148092-ESUN0D9YLN69GNIKMZP4/unsplash-image-tiTzBRnr7PY.jpg Faculty Overview https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1658240548031-84N5NUC3MA8GZD7C7Y84/unsplash-image-sY0wzQGMF8A.jpg Faculty Overview https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1658240591696-W0EERPYIVQGSR0QE7IPZ/unsplash-image-0W4XLGITrHg.jpg Faculty Overview https://sysbio.med.harvard.edu/marcos-simoes-costa daily 0.75 2023-01-10 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1670446571858-FRHXQLCHUY5RCW9NBMGT/unsplash-image-TcE45yIzJA0.jpg Marcos Simoes-Costa - Marcos Simoes-Costa Lab Multicellular organisms are formed by a large number of cell types, which serve as the components of tissues and organs. In the Simoes-Costa Lab, we study how cellular diversity arises during vertebrate embryonic development. We employ systems-level approaches to decode the molecular programs that drive changes in cell identity. Our research group is particularly interested in how gene regulatory networks operate in space to generate complex arrangements of cells. Gene regulatory networks in embryonic development: Cellular diversity arises from the establishment of distinct molecular states in stem cell populations. We study how gene regulatory networks are able to transform cell identity to generate specialized tissues. Our model of choice is an ectodermal stem cell population known as the neural crest. Neural crest cells are able to migrate throughout the developing embryo to give rise to neurons, pigment cells, and skeletal cells. The spatial control of cell fate commitment: Tissues and organs have complex tridimensional structures, and their assembly relies upon the precise placement of cell types in space. As a result, differentiation must be coupled with the extracellular signals that pattern the early embryo. We are investigating how environmental information is processed by the genome to ensure cells differentiate at the right time and place. Reactivation of developmental gene circuits in cancers: Occasionally, development gene circuits that should be silenced during differentiation are abnormally reactivated in adult cells. This may lead to the re-emergence of embryonic behaviors and initiate malignant transformation. We study the biology of ectodermal cancers to understand how stem cell identity is coopted during tumorigenesis and metastasis. https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1667399977509-LI6EXOJW1UNN63M5P8KP/thumbnail_image002.jpg Marcos Simoes-Costa - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://sysbio.med.harvard.edu/publications daily 0.75 2023-08-28 https://sysbio.med.harvard.edu/comingsoon daily 0.75 2023-01-10 https://sysbio.med.harvard.edu/alumni daily 0.75 2025-11-25 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1657127753552-EJLDEM7DGPYKO1VB23FV/Lital+Bentovim.jpg Alumni https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1658240879338-PHTSDO5BGIF89CDE1P0X/josep.jpg Alumni https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1658863411164-UEYLZ0MGGY4N2LS89AMH/kelly+brock.jpg Alumni 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https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/55733b81-2de8-462b-9a21-b23a4e9e48c2/09132022+Antoine.jpg Alumni https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1658672335299-P8O1CN9D9K0R1SZK032K/greg+baker.jpeg Alumni https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/009e8e31-ad8c-4a6e-994c-aef742c8e31a/simon.png Alumni https://sysbio.med.harvard.edu/department-core-goals daily 0.75 2023-05-02 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1683035353561-2WCN5UVOUJ743VZHQY1W/unsplash-image-WTYHayV4-j0.jpg https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/1683035393934-GZ1K2S39DEYQ3RL7OCUI/unsplash-image-sbE9zbcuiZs.jpg https://sysbio.med.harvard.edu/action-items daily 0.75 2023-05-25 https://sysbio.med.harvard.edu/resources-for-disabled-staff-and-faculty daily 0.75 2026-03-10 https://sysbio.med.harvard.edu/department-retreat-2022-1 daily 0.75 2023-06-13 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/9f1390eb-a6af-4696-acbe-d65db167f097/Breakout+Session+with+Galit2.jpg Department Retreat 2023 Breakout Session on day one https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/3a6ee639-43ef-4ed1-aca6-7572eba6cc8a/Dinner+Night+2.jpg Department Retreat 2023 Dinner at the retreat! https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/2356d390-0fc5-4a50-92d5-7f3453692629/First+Session.jpg Department Retreat 2023 Science Talk at the retreat https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/a3bfa275-c0ba-466b-b10c-93483bd80d04/Poster+Session+Night+1.jpg Department Retreat 2023 Poster Session Night 1 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/6ba8e9e3-22db-4eb2-b4c5-624346f0200f/Poster+Session+night+1c.jpg Department Retreat 2023 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https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/e9f1ed71-64a5-4d00-84ba-5e9c010d5ae5/grad+student+2.jpg Department Retreat 2023 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/42b9e527-f3e4-47fe-99aa-450612602a8d/friends+2.jpg Department Retreat 2023 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/889f2062-393e-4e40-8373-5937ab7894d2/grad+students.jpg Department Retreat 2023 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/3a67b974-dbf1-4bbf-aac0-575d34a6e1f4/friends%21.jpg Department Retreat 2023 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/71adb71c-e312-4f33-87f9-1a452308eee4/markus+talk.jpg Department Retreat 2023 https://images.squarespace-cdn.com/content/v1/628fa94dedb3df219547d5f9/fdb701f3-2f1a-4d4b-a372-d36e256f045a/games+with+the+crew.jpg Department Retreat 2023 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