Research & Scholarship

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  • Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise. Cell Sanford, J. A., Nogiec, C. D., Lindholm, M. E., Adkins, J. N., Amar, D., Dasari, S., Drugan, J. K., Fernandez, F. M., Radom-Aizik, S., Schenk, S., Snyder, M. P., Tracy, R. P., Vanderboom, P., Trappe, S., Walsh, M. J., Molecular Transducers of Physical Activity Consortium, Adkins, J. N., Amar, D., Dasari, S., Drugan, J. K., Evans, C. R., Fernandez, F. M., Li, Y., Lindholm, M. E., Nogiec, C. D., Radom-Aizik, S., Sanford, J. A., Schenk, S., Snyder, M. P., Tomlinson, L., Tracy, R. P., Trappe, S., Vanderboom, P., Walsh, M. J., Alekel, D. L., Bekirov, I., Boyce, A. T., Boyington, J., Fleg, J. L., Joseph, L. J., Laughlin, M. R., Maruvada, P., Morris, S. A., McGowan, J. A., Nierras, C., Pai, V., Peterson, C., Ramos, E., Roary, M. C., Williams, J. P., Xia, A., Cornell, E., Rooney, J., Miller, M. E., Ambrosius, W. T., Rushing, S., Stowe, C. L., Rejeski, W. J., Nicklas, B. J., Pahor, M., Lu, C., Trappe, T., Chambers, T., Raue, U., Lester, B., Bergman, B. C., Bessesen, D. H., Jankowski, C. M., Kohrt, W. M., Melanson, E. L., Moreau, K. L., Schauer, I. E., Schwartz, R. S., Kraus, W. E., Slentz, C. A., Huffman, K. M., Johnson, J. L., Willis, L. H., Kelly, L., Houmard, J. A., Dubis, G., Broskey, N., Goodpaster, B. H., Sparks, L. M., Coen, P. M., Cooper, D. M., Haddad, F., Rankinen, T., Ravussin, E., Johannsen, N., Harris, M., Jakicic, J. M., Newman, A. B., Forman, D. D., Kershaw, E., Rogers, R. J., Nindl, B. C., Page, L. C., Stefanovic-Racic, M., Barr, S. L., Rasmussen, B. B., Moro, T., Paddon-Jones, D., Volpi, E., Spratt, H., Musi, N., Espinoza, S., Patel, D., Serra, M., Gelfond, J., Burns, A., Bamman, M. M., Buford, T. W., Cutter, G. R., Bodine, S. C., Esser, K., Farrar, R. P., Goodyear, L. J., Hirshman, M. F., Albertson, B. G., Qian, W., Piehowski, P., Gritsenko, M. A., Monore, M. E., Petyuk, V. A., McDermott, J. E., Hansen, J. N., Hutchison, C., Moore, S., Gaul, D. A., Clish, C. B., Avila-Pacheco, J., Dennis, C., Kellis, M., Carr, S., Jean-Beltran, P. M., Keshishian, H., Mani, D. R., Clauser, K., Krug, K., Mundorff, C., Pearce, C., Ivanova, A. A., Ortlund, E. A., Maner-Smith, K., Uppal, K., Zhang, T., Sealfon, S. C., Zavlasky, E., Nair, V., Li, S., Jain, N., Ge, Y., Sun, Y., Nudelman, G., Ruf-Zamojski, F., Smith, G., Pincas, N., Rubenstein, A., Amper, M. A., Seenarine, N., Lappalainen, T., Lanza, I. R., Nair, K. S., Klaus, K., Montgomery, S. B., Smith, K. S., Gay, N. R., Zhao, B., Hung, C. J., Zebarjadi, N., Balliu, B., Fresard, L., Burant, C. F., Li, J. Z., Kachman, M., Soni, T., Raskind, A. B., Gerszten, R., Robbins, J., Ilkayeva, O., Muehlbauer, M. J., Newgard, C. B., Ashley, E. A., Wheeler, M. T., Jimenez-Morales, D., Raja, A., Dalton, K. P., Zhen, J., Kim, Y. S., Christle, J. W., Marwaha, S., Chin, E. T., Hershman, S. G., Hastie, T., Tibshirani, R., Rivas, M. A. 2020; 181 (7): 1464?74


    Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease.

    View details for DOI 10.1016/j.cell.2020.06.004

    View details for PubMedID 32589957

  • Impact of admixture and ancestry on eQTL analysis and GWAS colocalization in GTEx. Genome biology Gay, N. R., Gloudemans, M., Antonio, M. L., Abell, N. S., Balliu, B., Park, Y., Martin, A. R., Musharoff, S., Rao, A. S., Aguet, F., Barbeira, A. N., Bonazzola, R., Hormozdiari, F., Ardlie, K. G., Brown, C. D., Im, H. K., Lappalainen, T., Wen, X., Montgomery, S. B. 2020; 21 (1): 233


    Population structure among study subjects may confound genetic association studies, and lack of proper correction can lead to spurious findings. The Genotype-Tissue Expression (GTEx) project largely contains individuals of European ancestry, but the v8 release also includes up to 15% of individuals of non-European ancestry. Assessing ancestry-based adjustments in GTEx improves portability of this research across populations and further characterizes the impact of population structure on GWAS colocalization.Here, we identify a subset of 117 individuals in GTEx (v8) with a high degree of population admixture and estimate genome-wide local ancestry. We perform genome-wide cis-eQTL mapping using admixed samples in seven tissues, adjusted by either global or local ancestry. Consistent with previous work, we observe improved power with local ancestry adjustment. At loci where the two adjustments produce different lead variants, we observe 31 loci (0.02%) where a significant colocalization is called only with one eQTL ancestry adjustment method. Notably, both adjustments produce similar numbers of significant colocalizations within each of two different colocalization methods, COLOC and FINEMAP. Finally, we identify a small subset of eQTL-associated variants highly correlated with local ancestry, providing a resource to enhance functional follow-up.We provide a local ancestry map for admixed individuals in the GTEx v8 release and describe the impact of ancestry and admixture on gene expression, eQTLs, and GWAS colocalization. While the majority of the results are concordant between local and global ancestry-based adjustments, we identify distinct advantages and disadvantages to each approach.

    View details for DOI 10.1186/s13059-020-02113-0

    View details for PubMedID 32912333

  • ReprDB and panDB: minimalist databases with maximal microbial representation MICROBIOME Zhou, W., Gay, N., Oh, J. 2018; 6: 15


    Profiling of shotgun metagenomic samples is hindered by a lack of unified microbial reference genome databases that (i) assemble genomic information from all open access microbial genomes, (ii) have relatively small sizes, and (iii) are compatible to various metagenomic read mapping tools. Moreover, computational tools to rapidly compile and update such databases to accommodate the rapid increase in new reference genomes do not exist. As a result, database-guided analyses often fail to profile a substantial fraction of metagenomic shotgun sequencing reads from complex microbiomes.We report pipelines that efficiently traverse all open access microbial genomes and assemble non-redundant genomic information. The pipelines result in two species-resolution microbial reference databases of relatively small sizes: reprDB, which assembles microbial representative or reference genomes, and panDB, for which we developed a novel iterative alignment algorithm to identify and assemble non-redundant genomic regions in multiple sequenced strains. With the databases, we managed to assign taxonomic labels and genome positions to the majority of metagenomic reads from human skin and gut microbiomes, demonstrating a significant improvement over a previous database-guided analysis on the same datasets.reprDB and panDB leverage the rapid increases in the number of open access microbial genomes to more fully profile metagenomic samples. Additionally, the databases exclude redundant sequence information to avoid inflated storage or memory space and indexing or analyzing time. Finally, the novel iterative alignment algorithm significantly increases efficiency in pan-genome identification and can be useful in comparative genomic analyses.

    View details for PubMedID 29347966

  • Ferrofluid-Based Droplet Interface Bilayer Networks. Langmuir : the ACS journal of surfaces and colloids Makhoul-Mansour, M., Zhao, W., Gay, N., O'Connor, C., Najem, J. S., Mao, L., Freeman, E. C. 2017; 33 (45): 13000?13007


    Droplet interface bilayer (DIB) networks allow for the construction of stimuli-responsive, membrane-based materials. Traditionally used for studying cellular transport phenomena, the DIB technique has proven its practicality when creating structured droplet networks. These structures consist of aqueous compartments capable of exchanging their contents across membranous barriers in a regulated fashion via embedded biomolecules, thus approximating the activity of natural cellular systems. However, lipid bilayer networks are often static and incapable of any reconfiguration in their architecture. In this study, we investigate the incorporation of a magnetic fluid or ferrofluid within the droplet phases for the creation of magnetically responsive DIB arrays. The impact of adding ferrofluid to the aqueous phases of the DIB networks is assessed by examining the bilayers' interfacial tensions, thickness, and channel activity. Once compatibility is established, potential applications of the ferrofluid-enabled DIBs are showcased by remotely modifying membrane qualities through magnetic fields. Ferrofluids do not significantly alter the bilayers' properties or functionality and can therefore be safely embedded within the DIB platform, allowing for remote manipulation of the interfacial bilayer properties.

    View details for PubMedID 29043824

  • Draft Genome Sequence of Cloacibacterium normanense NRS-1 Isolated from Municipal Wastewater. Genome announcements Gay, N. R., Fleming, E., Oh, J. 2016; 4 (6)


    Cloacibacterium normanense is a Gram-negative bacterium recovered from untreated human wastewater. Given its high abundance in wastewater and its apparent absence in human stool, it may contribute to biological phosphate removal. Here, we perform a whole-genome sequence of C. normanense NRS-1(T) and examine particular features of this draft genome.

    View details for DOI 10.1128/genomeA.01397-16

    View details for PubMedID 27979947

    View details for PubMedCentralID PMC5159580

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