Bio

Honors & Awards


  • NRSA Postdoctoral Fellowship, NIH - NHGRI (2013)
  • Dean's Postdoctoral Fellowship, Stanford University (2012-2013)
  • Graduate Research Fellowship, NSF (2007-2010)
  • Gates Cambridge Graduate Scholarship [Offered], Cambridge University (2005)
  • Member, Phi Beta Kappa (2004)

Professional Education


  • Doctor of Philosophy, University of California Berkeley (2011)

Stanford Advisors


Research & Scholarship

Current Research and Scholarly Interests


I am a molecular biologist and geneticist working in the field of human genomics. I am fascinated by the evolutionary history reflected in the human genome and the ways in which it has impacted disease susceptibilities in different populations.

For my dissertation research at UC Berkeley, I worked on the disease side of the equation, studying the role of meiotic recombination machinery in the divergent eukaryotic parasite Giardia intestinalis. This research also allowed me to investigate broader evolutionary questions relating to the evolution of meiosis and sex.

Now, for my postdoctoral work, I am applying my expertise in molecular biology to develop new tools for working with and analyzing ancient DNA. This project has enabled me to build a solid background in human genomics and population genetics, which will serve as a foundation for my future work. I am now involved in several projects related to clinical genomics and genome interpretation and am currently a freelance biocurator for Personalis, Inc.

Lab Affiliations


Publications

Journal Articles


  • Exome capture from saliva produces high quality genomic and metagenomic data. BMC genomics Kidd, J. M., Sharpton, T. J., Bobo, D., Norman, P. J., Martin, A. R., Carpenter, M. L., Sikora, M., Gignoux, C. R., Nemat-Gorgani, N., Adams, A., Guadalupe, M., Guo, X., Feng, Q., Li, Y., Liu, X., Parham, P., Hoal, E. G., Feldman, M. W., Pollard, K. S., Wall, J. D., Bustamante, C. D., Henn, B. M. 2014; 15 (1): 262

    Abstract

    Targeted capture of genomic regions reduces sequencing cost while generating higher coverage by allowing biomedical researchers to focus on specific loci of interest, such as exons. Targeted capture also has the potential to facilitate the generation of genomic data from DNA collected via saliva or buccal cells. DNA samples derived from these cell types tend to have a lower human DNA yield, may be degraded from age and/or have contamination from bacteria or other ambient oral microbiota. However, thousands of samples have been previously collected from these cell types, and saliva collection has the advantage that it is a non-invasive and appropriate for a wide variety of research.We demonstrate successful enrichment and sequencing of 15 South African KhoeSan exomes and 2 full genomes with samples initially derived from saliva. The expanded exome dataset enables us to characterize genetic diversity free from ascertainment bias for multiple KhoeSan populations, including new exome data from six HGDP Namibian San, revealing substantial population structure across the Kalahari Desert region. Additionally, we discover and independently verify thirty-one previously unknown KIR alleles using methods we developed to accurately map and call the highly polymorphic HLA and KIR loci from exome capture data. Finally, we show that exome capture of saliva-derived DNA yields sufficient non-human sequences to characterize oral microbial communities, including detection of bacteria linked to oral disease (e.g. Prevotella melaninogenica). For comparison, two samples were sequenced using standard full genome library preparation without exome capture and we found no systematic bias of metagenomic information between exome-captured and non-captured data.DNA from human saliva samples, collected and extracted using standard procedures, can be used to successfully sequence high quality human exomes, and metagenomic data can be derived from non-human reads. We find that individuals from the Kalahari carry a higher oral pathogenic microbial load than samples surveyed in the Human Microbiome Project. Additionally, rare variants present in the exomes suggest strong population structure across different KhoeSan populations.Jeffrey M Kidd and Thomas J Sharpton are contributed equally to this manuscript.

    View details for DOI 10.1186/1471-2164-15-262

    View details for PubMedID 24708091

  • Pulling out the 1%: Whole-Genome Capture for the Targeted Enrichment of Ancient DNA Sequencing Libraries. American journal of human genetics Carpenter, M. L., Buenrostro, J. D., Valdiosera, C., Schroeder, H., Allentoft, M. E., Sikora, M., Rasmussen, M., Gravel, S., Guillén, S., Nekhrizov, G., Leshtakov, K., Dimitrova, D., Theodossiev, N., Pettener, D., Luiselli, D., Sandoval, K., Moreno-Estrada, A., Li, Y., Wang, J., Gilbert, M. T., Willerslev, E., Greenleaf, W. J., Bustamante, C. D. 2013; 93 (5): 852-64

    Abstract

    Most ancient specimens contain very low levels of endogenous DNA, precluding the shotgun sequencing of many interesting samples because of cost. Ancient DNA (aDNA) libraries often contain <1% endogenous DNA, with the majority of sequencing capacity taken up by environmental DNA. Here we present a capture-based method for enriching the endogenous component of aDNA sequencing libraries. By using biotinylated RNA baits transcribed from genomic DNA libraries, we are able to capture DNA fragments from across the human genome. We demonstrate this method on libraries created from four Iron Age and Bronze Age human teeth from Bulgaria, as well as bone samples from seven Peruvian mummies and a Bronze Age hair sample from Denmark. Prior to capture, shotgun sequencing of these libraries yielded an average of 1.2% of reads mapping to the human genome (including duplicates). After capture, this fraction increased substantially, with up to 59% of reads mapped to human and enrichment ranging from 6- to 159-fold. Furthermore, we maintained coverage of the majority of regions sequenced in the precapture library. Intersection with the 1000 Genomes Project reference panel yielded an average of 50,723 SNPs (range 3,062-147,243) for the postcapture libraries sequenced with 1 million reads, compared with 13,280 SNPs (range 217-73,266) for the precapture libraries, increasing resolution in population genetic analyses. Our whole-genome capture approach makes it less costly to sequence aDNA from specimens containing very low levels of endogenous DNA, enabling the analysis of larger numbers of samples.

    View details for DOI 10.1016/j.ajhg.2013.10.002

    View details for PubMedID 24568772

  • Nuclear inheritance and genetic exchange without meiosis in the binucleate parasite Giardia intestinalis JOURNAL OF CELL SCIENCE Carpenter, M. L., Assaf, Z. J., Gourguechon, S., Cande, W. Z. 2012; 125 (10): 2523-2532

    Abstract

    The protozoan parasite Giardia intestinalis (also known as Giardia lamblia) is a major waterborne pathogen. During its life cycle, Giardia alternates between the actively growing trophozoite, which has two diploid nuclei with low levels of allelic heterozygosity, and the infectious cyst, which has four nuclei and a tough outer wall. Although the formation of the cyst wall has been studied extensively, we still lack basic knowledge about many fundamental aspects of the cyst, including the sources of the four nuclei and their distribution during the transformation from cyst into trophozoite. In this study, we tracked the identities of the nuclei in the trophozoite and cyst using integrated nuclear markers and immunofluorescence staining. We demonstrate that the cyst is formed from a single trophozoite by a mitotic division without cytokinesis and not by the fusion of two trophozoites. During excystation, the cell completes cytokinesis to form two daughter trophozoites. The non-identical nuclear pairs derived from the parent trophozoite remain associated in the cyst and are distributed to daughter cells during excystation as pairs. Thus, nuclear sorting (such that each daughter cell receives a pair of identical nuclei) does not appear to be a mechanism by which Giardia reduces heterozygosity between its nuclei. Rather, we show that the cyst nuclei exchange chromosomal genetic material, perhaps as a way to reduce heterozygosity in the absence of meiosis and sex, which have not been described in Giardia. These results shed light on fundamental aspects of the Giardia life cycle and have implications for our understanding of the population genetics and cell biology of this binucleate parasite.

    View details for DOI 10.1242/jcs.103879

    View details for Web of Science ID 000306107000018

    View details for PubMedID 22366460

  • The Genome of Naegleria gruberi Illuminates Early Eukaryotic Versatility CELL Fritz-Laylin, L. K., Prochnik, S. E., Ginger, M. L., Dacks, J. B., Carpenter, M. L., Field, M. C., Kuo, A., Paredez, A., Chapman, J., Pham, J., Shu, S., Neupane, R., Cipriano, M., Mancuso, J., Tu, H., Salamov, A., Lindquist, E., Shapiro, H., Lucas, S., Grigoriev, I. V., Cande, W. Z., Fulton, C., Rokhsar, D. S., Dawson, S. C. 2010; 140 (5): 631-642

    Abstract

    Genome sequences of diverse free-living protists are essential for understanding eukaryotic evolution and molecular and cell biology. The free-living amoeboflagellate Naegleria gruberi belongs to a varied and ubiquitous protist clade (Heterolobosea) that diverged from other eukaryotic lineages over a billion years ago. Analysis of the 15,727 protein-coding genes encoded by Naegleria's 41 Mb nuclear genome indicates a capacity for both aerobic respiration and anaerobic metabolism with concomitant hydrogen production, with fundamental implications for the evolution of organelle metabolism. The Naegleria genome facilitates substantially broader phylogenomic comparisons of free-living eukaryotes than previously possible, allowing us to identify thousands of genes likely present in the pan-eukaryotic ancestor, with 40% likely eukaryotic inventions. Moreover, we construct a comprehensive catalog of amoeboid-motility genes. The Naegleria genome, analyzed in the context of other protists, reveals a remarkably complex ancestral eukaryote with a rich repertoire of cytoskeletal, sexual, signaling, and metabolic modules.

    View details for DOI 10.1016/j.cell.2010.01.032

    View details for Web of Science ID 000275197400013

    View details for PubMedID 20211133

  • Using Morpholinos for Gene Knockdown in Giardia intestinalis EUKARYOTIC CELL Carpenter, M. L., Cande, W. Z. 2009; 8 (6): 916-919

    Abstract

    We used translation-blocking morpholinos to reduce protein levels in Giardia intestinalis. Twenty-four hours after electroporation with morpholinos targeting either green fluorescent protein or kinesin-2b, levels of these proteins were reduced by 60%. An epitope-tagged transgene can also be used as a reporter for morpholino efficacy with targets lacking specific antibodies.

    View details for DOI 10.1128/EC.00041-09

    View details for Web of Science ID 000266640100012

    View details for PubMedID 19377039

  • The Trichoplax genome and the nature of placozoans NATURE Srivastava, M., Begovic, E., Chapman, J., Putnam, N. H., Hellsten, U., Kawashima, T., Kuo, A., Mitros, T., Salamov, A., Carpenter, M. L., Signorovitch, A. Y., Moreno, M. A., Kamm, K., Grimwood, J., Schmutz, J., Shapiro, H., Grigoriev, I. V., Buss, L. W., Schierwater, B., Dellaporta, S. L., Rokhsar, D. S. 2008; 454 (7207): 955-U19

    Abstract

    As arguably the simplest free-living animals, placozoans may represent a primitive metazoan form, yet their biology is poorly understood. Here we report the sequencing and analysis of the approximately 98 million base pair nuclear genome of the placozoan Trichoplax adhaerens. Whole-genome phylogenetic analysis suggests that placozoans belong to a 'eumetazoan' clade that includes cnidarians and bilaterians, with sponges as the earliest diverging animals. The compact genome shows conserved gene content, gene structure and synteny in relation to the human and other complex eumetazoan genomes. Despite the apparent cellular and organismal simplicity of Trichoplax, its genome encodes a rich array of transcription factor and signalling pathway genes that are typically associated with diverse cell types and developmental processes in eumetazoans, motivating further searches for cryptic cellular complexity and/or as yet unobserved life history stages.

    View details for DOI 10.1038/nature07191

    View details for Web of Science ID 000258591000030

    View details for PubMedID 18719581

  • Evidence for karyogamy and exchange of genetic material in the binucleate intestinal parasite Giardia intestinalis SCIENCE Poxleitner, M. K., Carpenter, M. L., Mancuso, J. J., Wang, C. R., Dawson, S. C., Cande, W. Z. 2008; 319 (5869): 1530-1533

    Abstract

    The diplomonad parasite Giardia intestinalis contains two functionally equivalent nuclei that are inherited independently during mitosis. Although presumed to be asexual, Giardia has low levels of allelic heterozygosity, indicating that the two nuclear genomes may exchange genetic material. Fluorescence in situ hybridization performed with probes to an episomal plasmid suggests that plasmids are transferred between nuclei in the cyst, and transmission electron micrographs demonstrate fusion between cyst nuclei. Green fluorescent protein fusions of giardial homologs of meiosis-specific genes localized to the nuclei of cysts, but not the vegetative trophozoite. These data suggest that the fusion of nuclei, or karyogamy, and subsequently somatic homologous recombination facilitated by the meiosis gene homologs, occur in the giardial cyst.

    View details for DOI 10.1126/science.1153752

    View details for Web of Science ID 000253943800040

    View details for PubMedID 18339940

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