Research:

Mammalian genome is extensively folded to form complex three-dimensional (3D) chromatin organization to facilitate functional interactions. These 3D structures and functional interactions are dynamics. Understanding these complex functional interactions and their variations will not only advance fundamental biological knowledge, but also provide novel insights into human disease that could lead to new treatment paradigms.
Our research focus on the development and application of advanced genomic technologies to decipher the genome structures, their three-dimensional (3D) organizations and how they modulate molecular phenotypes and complex traits. Our lab pioneered in pair-end-tag (PET) sequencing strategies to advance our ability to understand genome variation and transcription regulation in shaping cellular behavior. In recent years, we developed a suite of approaches including ChIA-PET, ChIA-Drop and ChIATAC to map 3D chromatin conformation which have transformed our understanding in how noncoding elements regulate transcription during development and disease states. We further improved these assays to derive single cell and single molecule resolution for studying complex genome structural variation, specifically, the extrachromosomal DNA (ecDNA) function in cancer. In addition, as one of the pioneers in establishing long-read technologies, we leverage advances in single-molecule, long-read sequencing methods to better identify complex structural variants of ecDNA, their evolution and impacts on ecDNA functions.

Selected Publications:

Yanfen Zhu, Amit D. Gujar, Chee-Hong Wong, Harianto Tjong, Chew Yee Ngan, Liang Gong, Yi-An Chen, Hoon Kim, Jihe Liu, Meihong Li, Adam Mil-Homens, Rahul Maurya, Chris Kuhlberg, Fanyue Sun, Eunhee Yi, Ana C. deCarvalho, Yijun Ruan, Roel G.W. Verhaak and Chia-Lin Wei. Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription. Cancer Cell (2021) 39(5):694 May 10, doi: 10.1016/j.ccell.2021.03.006.

Ngan CY, Wong CH, Tjong H, Wang W, Goldfeder R, Choi C, He H, Gong L, Lin J, Urban B, Chow J, Li M, Lim J, VPhilip V, Murray SA, Wang H, Wei CL. Chromatin interaction analyses elucidate the roles of PRC2-bound silencers in mouse development. Nat Genet. 2020 Mar;52(3):264-272.

Bertolini JA, Favaro R, Zhu Y, Pagin M, Ngan CY, Wong CH, Tjong H, Vermunt MW, Martynoga B, Barone C, Mariani J, Cardozo MJ, Tabanera N, Zambelli F, Mercurio S, Ottolenghi S, Robson P, Creyghton MP, Bovolenta P, Pavesi G, Guillemot F, Nicolis SK, Wei CL. Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance. Cell Stem Cell.2019. 24(3):462

Meizhen Zheng, Simon Zhongyuan Tian, Daniel Capurso, Minji Kim, Rahul Maurya, Byoungkoo Lee, Emaly Piecuch, Liang Gong, Jacqueline Jufen Zhu, Chee Hong Wong, Chew Yee Ngan, Ping Wang, Xiaoan Ruan, Chia-Lin Wei, Yijun Ruan. Multiplex Chromatin Interaction Analysis by Droplet Sequencing with Single Molecule Precision. Nature. 2019 Feb;566(7745):558-562.

Haoxi Chai, Harianto Tjong, Peng Li, Wei Liao, Ping Wang, Chee Hong Wong, Chew Yee Ngan, Warren J Leonard, Chia-Lin Wei, Yijun Ruan. ChIATAC is an efficient strategy for multi-omics mapping of 3D epigenomes from low-cell inputs. Nat. Comm. 2023 14(1):213.

Liang Gong, Chee-Hong Wong, Wei-Chung Cheng, Harianto Tjong, Francesca Menghi, Chew Yee Ngan, Edison T. Liu, Chia-Lin Wei (2018). Picky Comprehensively Detects High Resolution Structural Variants in Nanopore Long Reads. Nature Methods 15 (6), 455-460. doi: 10.1038/s41592-018-0002-6

Zhang Y, Wong CH, Birnbaum RY, Li G, Favaro R, Ngan CY, Lim J, Tai E, Poh HM, Wong E, Mulawadi FH, Sung WK, Nicolis S, Ahituv N, Ruan Y, Wei CL. Chromatin connectivity maps reveal dynamic promoter-enhancer long-range associations. Nature. 2013 Dec 12;504(7479):306-10.

Research

My research group is focused on building robust and scalable enabling technologies to study the organization of chromosomes in 3D space, the interactions they participate in at the inter- and intra-chromosomal level, and the associated RNAs and proteins that occupy functionally relevant sites. The motivation for this work is to better understand the mechanisms by which the organization and composition of genomic intervals relevant for health and disease impact the essential DNA transactions of transcription, replication, and repair. We also are committed to building ecosystems supported by open-source software, low-cost hardware, and extensive documentation to democratize the adoption of advanced single cell and spatial approaches in order to facilitate their application in a broad range of research settings.

Selected Publications

Liu, Y.*, McGann, C.D.*, Krebs, M., Perkins Jr., T.A., Fields, R., Camplisson, C.K., Nwizugbo, D.Z., Hsu, C., Avanessian, S.C., Tsue, A.F., Kania, E.E., Shechner, D.M., Beliveau, B.J.†, Schweppe, D.K.† DNA O-MAP uncovers the molecular neighborhoods associated with specific genomic loci. eLife https://elifesciences.org/reviewed-preprints/102489 (2024). [*Co-first authors] [†Co-corresponding authors]

Attar, S., Browning, V.E.*, Krebs, M.*, Liu, Y., Nichols, E.K., Tsue, A.F., Shechner, D.M., Shendure, J., Lieberman, J.A., Schweppe, D.K., Akilesh, S.†, Beliveau, B.J.† Efficient and highly amplified imaging of nucleic acid targets in cellular and histopathological samples with pSABER. Nature Methods https://doi.org/10.1038/s41592-024-02512-2 (2024). [*Equal author contribution] [†Co-corresponding authors]

Aguilar, R., Camplisson, C.K., Lin, Q., Miga, K.H., Noble, W.S.†, Beliveau, B.J.† Tigerfish designs oligonucleotide-based in situ hybridization probes targeting intervals of highly repetitive DNA at the scale of genomes. Nature Communications 15, 1027 (2024). [†Co-corresponding authors]

Hershberg, E.A.*, Camplisson, C.K.*, Close, J.L., Attar, S., Chern, R., Liu, Y., Akilesh, S., Nicovich, P.R., Beliveau, B.J. PaintSHOP enables the interactive design of transcriptome- and genome-scale oligonucleotide FISH experiments. Nature Methods 18, 937–944 (2021). [*Equal author contribution]

Kishi, J.Y.*, Lapan, S.W.*, Beliveau, B.J.*,†, West, E.R.*, Zhu, A., Sasaki, H.M., Saka, S.K., Wang, Y., Cepko, C.L.†, Yin, P.† SABER amplifies FISH: enhanced multiplexed imaging of RNA and DNA in cells and tissues. Nature Methods 16, 533–544 (2019). [*Equal author contribution] [†Co-corresponding authors]

additional publications

Research:

Our research focuses on the development of machine learning techniques for application to problems in molecular biology. We approach these problems using Bayesian techniques such as hidden Markov models, as well as support vector machines and related, non-Bayesian methods. Much of our work addresses two core problems in machine learning: incorporating domain-specific prior knowledge and learning from heterogeneous data. We apply our techniques to problems such as automatic gene finding, microarray expression analysis, gene functional classification, and protein remote homology detection.

Selected Publications:

J Liu, JT Halloran, JA Bilmes, RM Daza, C Lee, EM Mahen, D Prunkard, C Song, S Blau, MO Dorschner, VK Gadi, J Shendure, CA Blau, and WS Noble. “Comprehensive statistical inference of the clonal structure of cancer from multiple biopsies.” Scientific Reports. 7(1):16943, 2017.

MW Libbrecht, JA Bilmes and WS Noble. “Choosing non-redundant representative subsets of protein sequence data sets using submodular optimization.” Proteins. 86(4):454–466, 2018.

J Liu, D Lin, G Yardımcı, and WS Noble. “Unsupervised embedding of single-cell Hi-C data.” Bioinformatics (Proceedings of the ISMB). 34(13):i96–i104, 2018.

W Bai, J Bilmes and WS Noble. “Submodular generalized matching for peptide identification in tandem mass spectrometry.” IEEE Transactions in Computational Biology and Bioinformatics. 16(4):1168–1181, 2019.

A Bertero, PA Fields, V Ramani, G Bonora, G Yardımcı, H Reinecke, L Pabon, WS Noble, J Shendure, CE Murry. “Dynamics of genome reorganization during human cardiogenesis reveal an RBM20- dependent splicing factory.” Nature Communications. 10(1):1538, 2019.

DF Read, K Cook, YY Lu, K Le Roch, and WS Noble. “Predicting gene expression in the human malaria parasite Plasmodium falciparum.” PLOS Computational Biology. 15(9):e1007329, 2019.

J Schreiber, TJ Durham, J Bilmes, WS Noble. “Multi-scale deep tensor factorization learns a latent representation of the human epigenome.” Genome Biology. 21:81, 2020.

additional publication listings available via PubMed

Research

I have been in love with DNA for as long as I can remember.  I chose to study replication because it is central to the biological role of DNA as the molecule of inheritance, and I found in Baker’s yeast the perfect organism to investigate this fundamental process. 

Research is conducted in collaboration with Professor M. K. Raghuraman (Raghu).  We are studying the regulation of replication that ensures that each chromosome is duplicated in a timely and precise way, and are characterizing the consequences for chromosomes when these processes go awry.  Although the chromosomes of the budding yeast are orders of magnitude smaller than those of plants and animals, they are organized for replication in much the same way: replication occurs from multiple, closely-spaced origins and different parts of a chromosome are replicated at different times during the S phase of the cell cycle, using machinery that is conserved from yeast to humans.  Thus, studying how this small organism replicates and maintains its chromosomes gives us insights into how the same processes occur—or go awry—in our own cells.

Nearly 50 years ago, we pioneered the use of 2-dimensional gel electrophoresis techniques to map specific replication origins and to determine the efficiency with which they are activated.  In the early days of DNA microarrays we developed methods and algorithms to study replication on a genome wide scale.  While we now also use DNA sequencing to answer some questions about genome structure and replication, we find gels and Southern hybridization are often still the best tools to answer the questions that interest us. 

While this work continues, in collaborations with Maitreya Dunham’s lab, we are also exploring the changes to chromosomes that occur during laboratory evolution and replicative aging and find they are often the consequence of an error in replication.  Growing yeast cells continuously for many weeks in chemostats limiting for sulfur invariably results in the amplification of the gene that encodes the primary sulfate transporter, SUL1.  While that outcome itself isn’t that surprising, the mechanisms that cells use to bring about the amplification are novel.  The primary form of amplicon of the SUL1 gene and its adjacent origin of replication is a triplicated chromosomal fragment with the center copy in an inverted orientation.  We proposed that an error in replication fork progressions explains  how this particular structure is generated.  When we interfere with this mechanism by mutating different genes involved in DNA replication or chromosome maintenance, we uncovered other mechanisms that cells use to achieve the selective benefits from SUL1 amplification.  Structures similar to the yeast SUL1 amplicons have been found in humans where they are often associated with genetic disorders.  We have also used chemostats to explore genomic changes that occur during aging of yeast cells.  We propose that aberrant repair of broken replication forks generates branched chromosomes that cannot be properly segregated at division—thereby limiting yeast’s life span.  Might these errors also be contributing to human aging?  Stay tuned!

Selected Publications

Brewer, B. J. and W. L. Fangman (1987). “The localization of replication origins on ARS plasmids in S. cerevisiae.” Cell 51(3): 463-471; https://doi.org/10.1016/0092-8674(87)90642-8.

Raghuraman, M. K., E. A. Winzeler, D. Collingwood, S. Hunt, L. Wodicka, A. Conway, D. J. Lockhart, R. W. Davis, B. J. Brewer and W. L. Fangman (2001). “Replication dynamics of the yeast genome.” Science 294(5540): 115-121; https://doi.org/10.1126/science.294.5540.115.

Brewer, B. J., C. Payen, M. K. Raghuraman and M. J. Dunham (2011). “Origin-dependent inverted-repeat amplification: a replication-based model for generating palindromic amplicons.” PLoS Genet 7(3): e1002016; https://pmc.ncbi.nlm.nih.gov/articles/PMC3060070.

Sanchez, J. C., A. Ollodart, C. R. L. Large, C. Clough, G. M. Alvino, M. Tsuchiya, M. Crane, E. X. Kwan, M. Kaeberlein, M. J. Dunham, M. K. Raghuraman and B. J. Brewer (2019). “Phenotypic and Genotypic Consequences of CRISPR/Cas9 Editing of the Replication Origins in the rDNA of Saccharomyces cerevisiae.” Genetics 213(1): 229-249; https://pmc.ncbi.nlm.nih.gov/articles/PMC6727806.

Kwan, E. X., G. M. Alvino, K. L. Lynch, P. F. Levan, H. M. Amemiya, X. S. Wang, S. A. Johnson, J. C. Sanchez, M. A. Miller, M. Croy, S. B. Lee, M. Naushab, A. Bedalov, J. T. Cuperus, B. J. Brewer, C. Queitsch and M. K. Raghuraman (2023). “Ribosomal DNA replication time coordinates completion of genome replication and anaphase in yeast.” Cell Rep 42(3): 112161; https://pmc.ncbi.nlm.nih.gov/articles/PMC10142053.

Brewer, B. J., M. J. Dunham and M. K. Raghuraman (2024). “A unifying model that explains the origins of human inverted copy number variants.” PLoS Genet 20(1): e1011091; https://pmc.ncbi.nlm.nih.gov/articles/PMC10766186.

Brewer, B.J., R. Martin, E. Ramage, C. Payen, S. C. Di Rienzi, Y. Zhao, K. Van Sickle, J. I. Verhey, M. Zalusky, D. E. Miller, D., G. T. Ong, J. L.  McKee, G. M. Alvino, M. J. Dunham and M. K. Raghuraman (2026). “Telomeric amplicons of SUL1 and Y’ in yeast are generated by microhomology-mediated break induced replication occurring in cis.” PLoS Genetics, in minor revision. https://doi.org/10.64898/2026.04.07.716220.  Submitted April 17, 2026

Armstrong, J. O., E. X. Kwan, G. M. Alvino, M. K. Raghuraman, M. J. Dunham and B. J. Brewer. (2026) “Beyond ERCs: exploring catastrophic forms of rDNA instability in aging yeast.” PLoS Genetics, under review. https://doi.org/10.64898/2026.04.21.719800.  Submitted April 18, 2026

additional publication listings available via PubMed | CV

Research:

My laboratory uses the fruit fly Drosophila melanogaster as a genetic model system to understand the mechanisms underlying neurodegenerative disorders, such as Parkinson’s disease. Flies are a terrific system for this work because of the many powerful genetic tools that have been developed over the long history of their use as a model organism, and because recent work has established that neurodegenerative disorders can be successfully modeled using flies. At present, we are pursuing three different projects in the lab.

Mitochondrial quality control: The accumulation of damaged mitochondria is linked to aging and common neurodegenerative diseases. Previous work has shown that damaged mitochondria can be selectively degraded in the lysosome through a process termed mitophagy, but the underlying mechanisms were completely unknown until recently. Our work on the Parkinson’s disease-related factors PINK1 and Parkin helped establish that they play crucial roles in mitophagy. A major focus of our laboratory is now aimed at understanding how PINK1 and Parkin promote mitophagy, and to identify other components of this mitochondrial quality control apparatus.

Functional analysis of the glucocerebrosidase (GBA) gene: Mutations in the GBA gene are by far the most common genetic association with Parkinson’s disease. GBA encodes a lysosomal enzyme required for the breakdown of the sphingolipid glucocylceramide, suggesting that the accumulation of glucocylceramide and related sphingolipids upon mutational inactivation of GBA triggers the onset of Parkinson’s disease. We have created a fly model of GBAdeficiency and are using it to explore the mechanisms underlying this frequent cause of Parkinson’s disease.

Traumatic brain injury: Over the past several years it has become increasingly clear that traumatic brain injuries significantly increase the risk for developing neurodegenerative diseases years or even decades after the injury. We have recently created a fly model of traumatic brain injury and are using this model to explore the underlying mechanisms.

Selected Publications:

full list of lab publications available via PubMed

Research

Our research interests include proteomics, mass spectrometry and advanced technology development, mapping protein interactions and topologies in biological systems and chemical biology. We are developing new mass spectrometry technology and chemical approaches that allow insight in protein interaction networks in vivo.

Selected Publications

View publications on the Bruce Lab website

Research

The Dunham lab develops and applies genomic tools to study genome evolution and genetic variation in yeast and humans.  We utilize the budding yeasts as a testbed for technology development and as an experimentally tractable system for evolutionary genetics and genomics.  By leveraging these systems in creative ways, we hope to learn in molecular detail how cells evolve and the mechanisms by which they do so, addressing important open questions on mutation spectrum, genome structure, mechanisms and consequences of copy number change, genetic interactions, evolution of gene expression, and other fundamental topics. 

The lab is broadly organized into an experimental evolution group and a comparative functional genomics group.  Many projects also intersect my long-standing interest in how gene and chromosome copy number variation contributes to adaptation, and the mechanisms by which such variation arises.  When new technology to study these questions has been required, we have developed it, including methods for genome analysis and long term continuous culture. 

Current projects include understanding the costs and benefits of aneuploidy, evolving hybrid yeasts, building new instruments for continuous culture, functionally characterizing centromeres and replication origins across species, and developing high throughput methods for measuring the impact of genetic variation in yeast and humans.

Selected Publications

Experimental evolution of S. cerevisiae for caffeine tolerance alters multidrug resistance and TOR signaling pathways. Geck RC, Moresi NG, Anderson LM; yEvo Students; Brewer R, Renz TR, Taylor MB, Dunham MJ. G3. 2024 Jul 11:jkae148. doi: 10.1093/g3journal/jkae148. [Pubmed][G3][SRA][GitHub][PDF][bioRxiv]

Systematic profiling of ale yeast protein dynamics across fermentation and repitching. Garge RK, Geck RC, Armstrong JO, Dunn B, Boutz DR, Battenhouse A, Leutert M, Dang V, Jiang P, Kwiatkowski D, Peiser T, McElroy H, Marcotte EM, Dunham MJ. G3. 2024 Mar 6;14(3):jkad293. doi: 10.1093/g3journal/jkad293. PMID: 38135291 [Pubmed][G3][Shiny App][PDF][bioRxiv][Genes to Genomes blog][The Brü Lab podcast]

yEvo: a modular eukaryotic genetics and evolution research experience for high school students. Taylor MB*, Warwick AR*, Skophammer R, Boyer JM, Geck RC, Gunkelman K, Walson M, Rowley PA#, Dunham MJ# (*co-first authors, #co-corresponding authors). Ecol Evol. 2024 Jan 7;14(1):e10811. doi: 10.1002/ece3.10811. eCollection 2024 Jan. PMID: 38192907 [Pubmed][Ecology and Evolution][PDF][bioRxiv]

Caffeine-tolerant mutations selected through an at-home yeast experimental evolution teaching lab. Moresi NG, Geck RC, Skophammer R, Godin D, yEvo Students, Taylor MB, Dunham MJ. MicroPubl Biol. 2023 Feb 9;2023:10.17912/micropub.biology.000749. doi: 10.17912/micropub.biology.000749. eCollection 2023. PMID: 36855741 [Pubmed][microPublication Biology][PDF][bioRxiv][This Week in Microbiology podcast]

Functional interpretation, cataloging, and analysis of 1,341 glucose-6-phosphate dehydrogenase variants. Geck RC, Powell NR, Dunham MJ. AJHG. 2023 Feb 2;110:1–12. [Pubmed][AJHG][G6PDcat on GitHub][PDF][letter to the editor response][GitHub][PDF][bioRxiv][All of Us][All of Us in Spanish]

yEvo: Experimental evolution in high school classrooms selects for novel mutations and epistatic interactions that impact clotrimazole resistance in S. cerevisiae. Taylor MB, Skophammer R, Warwick AR, Geck RC, Boyer JM, yEvo Students, Walson M, Large CRL, Hickey AS, Rowley PA#, Dunham MJ# (#co-corresponding authors). G3. 2022 Nov 4;12(11):jkac246. doi: 10.1093/g3journal/jkac246. [Pubmed][G3][PDF][SRA][bioRxiv]

PacRAT: a program to improve barcode-variant mapping from PacBio long reads using multiple sequence alignment. Yeh CC*, Amorosi CJ*, Showman S, Dunham MJ. (*co-first authors). Bioinformatics. 2022 May 13;38(10):2927-2929. doi: 10.1093/bioinformatics/btac165. [Pubmed][Bioinformatics][GitHub][bioRxiv]

Massively parallel characterization of CYP2C9 variant enzyme activity and abundance. Amorosi CJ, Chiasson MA, McDonald MG, Wong LH, Sitko KA, Boyle G, Kowalski JP, Rettie AE, Fowler DM#, Dunham MJ# (co-corresponding authors). Am J Hum Genet. 2021 Sep 2;108(9):1735-1751. doi: 10.1016/j.ajhg.2021.07.001. [Pubmed][AJHG][PDF][bioRxiv][Science in Seattle]

Multiplexing Mutation Rate Assessment: Determining Pathogenicity of Msh2 Variants in S. cerevisiae. Ollodart AR, Yeh CC, Miller AW, Shirts BH, Gordon AS, Dunham MJ. Genetics. 2021 Apr 12;iyab058. doi: 10.1093/genetics/iyab058. [Pubmed][Genetics][PDF][bioRxiv][BioProject]

Transposable element mobilization in interspecific yeast hybrids. Heil CS, Patterson K, Hickey AS, Alcantara E, Dunham MJ. Genome Biol Evol. 2021 Mar 1;13(3):evab033. doi: 10.1093/gbe/evab033. [Pubmed][GBE][PMC][PDF][bioRxiv][BioProject]

additional publications available via Google Scholar

Research

The long-term goal of our laboratory is to understand the evolution, pathology and mechanisms of recent gene duplication and DNA transposition within the human genome.

Our research specifically addresses a new paradigm that has emerged in the past few years in which particular regions of the human genome have been shown active in the acquisition, duplication and dispersal of large gene-containing genomic segments.

We hypothesize that these ‘jumping genomic segments’ are part of an ongoing evolutionary process that results in a novel form of large-scale variation in human genomic DNA and contributes rapidly to primate gene evolution.

The large blocks of sequence similarity generated by this process, we further propose provide the substrates for aberrant recombination, thereby leading to recurrent and potentially pathogenic chromosomal structural rearrangements.

The general aims of our research are 
1) to investigate the molecular mechanism(s) responsible for such duplications; 
2) to evaluate their role in the evolution of the higher primate genome; and 
3) to assess their impact in contributing to polymorphism of both normal human chromosomes and chromosomes associated with genetic instability diseases.

Our approach has been to combine bioinformatics, large-scale comparative sequencing, phylogenetics and high-resolution FISH methods to address these questions.

We are committed to the further characterization of these complex regions of the genome and the development of assays to correlate their dynamic structure with chromosome function, gene evolution and human disease. My research philosophy combines various disciplines (evolutionary biology, human genetics/genomics and bioinformatics) to understand the mechanisms and consequences of novel forms of variation in the human genome. Such a synergism of various disciplines provides a powerful strategy to address biological processes of genome evolution. The development of tools and the conditions required to pursue such a holistic approach, with respect to studies of genome evolution, are unprecedented. With the advent of the information age, current large-scale sequencing of genomes and the development of powerful bioinformatics tools, such ‘complex’ and mulitfaceted research objectives will become increasingly tractable endeavors.

My overall goal is to contribute to this new era of genomics sciences as it applies to evolution and medicine and to impart the value of this scientific design, through teaching and mentorship, to the next generation of scientists.

Selected Publications

Girirajan S, Rosenfeld JA, Cooper GM, Antonacci F, Siswara P, Itsara A, Vives L, Walsh T, McCarthy SE, Baker C, Mefford HC, Kidd JM, Browning SR, Browning BL, Dickel DE, Levy DL, Ballif BC, Platky K, Farber DM, Gowans GC, Wetherbee JJ, Asamoah A, Weaver DD, Mark PR, Dickerson J, Garg BP, Ellingwood SA, Smith R, Banks VC, Smith W, McDonald MT, Hoo JJ, French BN, Hudson C, Johnson JP, Ozmore JR, Moeschler JB, Surti U, Escobar LF, El-Khechen D, Gorski JL, Kussmann J, Salbert B, Lacassie Y, Biser A, McDonald-McGinn DM, Zackai EH, Deardorff MA, Shaikh TH, Haan E, Friend KL, Fichera M, Romano C, Gecz J, Delisi LE, Sebat J, King MC, Shaffer LG, Eichler EE. (2010). A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay. Nat Genet Mar;42(3):203-9.

Alkan C, Kidd JM, Marques-Bonet T, Aksay G, Antonacci F, Hormozdiari F, Kitzman JO, Baker C, Malig M, Mutlu O, Sahinalp SC, Gibbs RA, Eichler EE. (2009). Personalized copy number and segmental duplication maps using next-generation sequencing. Nat Genet Oct;41(10):1061–7.

Marques-Bonet T, Kidd JM, Ventura M, Graves TA, Cheng Z, Hillier LW, Jiang Z, Baker C, Malfavon-Borja R, Fulton LA, Alkan C, Aksay G, Girirajan S, Siswara P, Chen L, Cardone MF, Navarro A, Mardis ER, Wilson RK, Eichler EE. (2009). A burst of segmental duplications in the genome of the African great ape ancestor. Nature Feb 12;457(7231):877–81.

Itsara A, Cooper GM, Baker C, Girirajan S, Li J, Absher D, Krauss RM, Myers RM, Ridker PM, Chasman DI, Mefford H, Ying P, Nickerson DA, Eichler EE. (2009). Population analysis of large copy number variants and hotspots of human genetic disease. Am J Hum Genet. Feb;84(2):148–61.

Kidd JM, Cooper GM, Donahue WF, Hayden HS, Sampas N, Graves T, Hansen N, Teague B, Alkan C, Antonacci F, Haugen E, Zerr T, Yamada NA, Tsang P, Newman TL, Tuzun E, Cheng Z, Ebling HM, Tusneem N, David R, Gillett W, Phelps KA, Weaver M, Saranga D, Brand A, Tao W, Gustafson E, McKernan K, Chen L, Malig M, Smith JD, Korn JM, McCarroll SA, Altshuler DA, Peiffer DA, Dorschner M, Stamatoyannopoulos J, Schwartz D, Nickerson DA, Mullikin JC, Wilson RK, Bruhn L, Olson MV, Kaul R, Smith DR, Eichler EE. (2008). Mapping and sequencing of structural variation from eight human genomes. Nature May 1;453(7191):56–64.

Jiang Z, Tang H, Ventura M, Cardone MF, Marques-Bonet T, She X, Pevzner P, Eichler EE. (2007). Ancestral reconstruction of segmental duplications reveals punctuated cores of human genome evolution. Nat Genet Nov;39(11):1361–1368 (7 Oct 2007).

additional publication listings available via PubMed

The Feder lab aims to uncover how the rapid evolution of pathogens and cancers within people exacerbates disease, and how a better understanding of this intra-host evolution can be harnessed to improve human health. We are particularly interested in how the complex environment of the human body shapes this process across spatial scales. From cellular coinfection mediating viral interaction, to heterogeneous tumor microenvironments creating distinct environmental niches, and to the diverse conditions that pathogens face in different organ systems, space is a critical driver of intra-host evolution, and failure to interrogate its effects limits our ability to understand disease. While spatially-resolved data is increasingly collected at higher resolution and frequency, our analytical tools to leverage these spatial data have not kept pace. We are meeting this need by developing new quantitative approaches to understand spatially-resolved intra-host genetic data across viral, bacterial and somatic domains of life.

Representative papers:

State-dependent evolutionary models reveal modes of solid tumour growth

Elevated HIV viral load is associated with higher recombination rate in vivo

Understanding patterns of HIV multi-drug resistance through models of temporal and spatial drug heterogeneity