Bio

Membership Organizations


  • OB/Gyn Interest Group, Financial Officer
  • Arbor Free Clinic
  • MSFC: Medical Students For Choice

Education & Certifications


  • Bachelor of Science, University of Michigan Ann Arbor, Biochemistry (2007)

Stanford Advisors


Service, Volunteer and Community Work


  • Project Suyana, University of Michigan (6/19/2010)

    PROJECT SUYANA's mission is to narrow disparities in rural regions in Puno, Peru and combat them with a sustainable approach utilizing culturally appropriate, community-based projects. We hope to enhance the viability of rural life through goodwill, community partnership and practical action.

    Location

    Ann Arbor, MI <br> Puno, Peru

  • Volunteer Pre-clinical student, Cardinal Free Clinics, Women's Health Clinic (3/1/2009)

    Location

    Stanford, CA

Personal Interests


Dancing, yoga, and eating.

Research & Scholarship

Current Research and Scholarly Interests


My research has two components. The first component is to elucidate population structure among the Native Americans in South America. Based on their genomic data, my goal is to understand migration patterns, infer bottlenecks, admixture events, and relationships between the different indigenous populations of South America.

The second part of my research deals with the genetic basis of preeclampsia, specifically in admixed populations which have undergone positive adaption. This work is done in collaboration with the Hospital Manuel Nuñez Butron in Puno, Peru, where the prevalence of preeclampsia is much higher than the world-wide estimate of 3-8%. In conjunction with our genotypic studies, I will be looking at gene expression studies of placental sections of women with and without preeclampsia. My goal as an MSTP student is to elucidate the genetic mechanism for this condition and continue its study from a clinical perspective as I go on to do my residency in obstetrics and gynecology.

Lab Affiliations


Publications

All Publications


  • HUMAN GENETICS The genetics of Mexico recapitulates Native American substructure and affects biomedical traits SCIENCE Moreno-Estrada, A., Gignoux, C. R., Carlos Fernandez-Lopez, J., Zakharia, F., Sikora, M., Contreras, A. V., Acuna-Alonzo, V., Sandoval, K., Eng, C., Romero-Hidalgo, S., Ortiz-Tello, P., Robles, V., Kenny, E. E., Nuno-Arana, I., Barquera-Lozano, R., Macin-Perez, G., Granados-Arriola, J., Huntsman, S., Galanter, J. M., Via, M., Ford, J. G., Chapela, R., Rodriguez-Cintron, W., Rodriguez-Santana, J. R., Romieu, I., Jose Sienra-Monge, J., del Rio Navarro, B., London, S. J., Ruiz-Linares, A., Garcia-Herrera, R., Estrada, K., Hidalgo-Miranda, A., Jimenez-Sanchez, G., Carnevale, A., Soberon, X., Canizales-Quinteros, S., Rangel-Villalobos, H., Silva-Zolezzi, I., Burchard, E. G., Bustamante, C. D. 2014; 344 (6189): 1280-1285

    Abstract

    Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide.

    View details for DOI 10.1126/science.1251688

    View details for Web of Science ID 000337077500040

    View details for PubMedID 24926019

  • Reconstructing the population genetic history of the Caribbean. PLoS genetics Moreno-Estrada, A., Gravel, S., Zakharia, F., McCauley, J. L., Byrnes, J. K., Gignoux, C. R., Ortiz-Tello, P. A., Martínez, R. J., Hedges, D. J., Morris, R. W., Eng, C., Sandoval, K., Acevedo-Acevedo, S., Norman, P. J., Layrisse, Z., Parham, P., Martínez-Cruzado, J. C., Burchard, E. G., Cuccaro, M. L., Martin, E. R., Bustamante, C. D. 2013; 9 (11)

    Abstract

    The Caribbean basin is home to some of the most complex interactions in recent history among previously diverged human populations. Here, we investigate the population genetic history of this region by characterizing patterns of genome-wide variation among 330 individuals from three of the Greater Antilles (Cuba, Puerto Rico, Hispaniola), two mainland (Honduras, Colombia), and three Native South American (Yukpa, Bari, and Warao) populations. We combine these data with a unique database of genomic variation in over 3,000 individuals from diverse European, African, and Native American populations. We use local ancestry inference and tract length distributions to test different demographic scenarios for the pre- and post-colonial history of the region. We develop a novel ancestry-specific PCA (ASPCA) method to reconstruct the sub-continental origin of Native American, European, and African haplotypes from admixed genomes. We find that the most likely source of the indigenous ancestry in Caribbean islanders is a Native South American component shared among inland Amazonian tribes, Central America, and the Yucatan peninsula, suggesting extensive gene flow across the Caribbean in pre-Columbian times. We find evidence of two pulses of African migration. The first pulse--which today is reflected by shorter, older ancestry tracts--consists of a genetic component more similar to coastal West African regions involved in early stages of the trans-Atlantic slave trade. The second pulse--reflected by longer, younger tracts--is more similar to present-day West-Central African populations, supporting historical records of later transatlantic deportation. Surprisingly, we also identify a Latino-specific European component that has significantly diverged from its parental Iberian source populations, presumably as a result of small European founder population size. We demonstrate that the ancestral components in admixed genomes can be traced back to distinct sub-continental source populations with far greater resolution than previously thought, even when limited pre-Columbian Caribbean haplotypes have survived.

    View details for DOI 10.1371/journal.pgen.1003925

    View details for PubMedID 24244192

  • Reconstructing the Population Genetic History of the Caribbean PLOS GENETICS Moreno-Estrada, A., Gravel, S., Zakharia, F., McCauley, J. L., Byrnes, J. K., Gignoux, C. R., Ortiz-Tello, P. A., Martinez, R. J., Hedges, D. J., Morris, R. W., Eng, C., Sandoval, K., Acevedo-Acevedo, S., Norman, P. J., Layrisse, Z., Parham, P., Martinez-Cruzado, J. C., Burchard, E. G., Cuccaro, M. L., Martin, E. R., Bustamante, C. D. 2013; 9 (11)
  • Purification and assay protocols for obtaining highly active Jumonji C demethylases ANALYTICAL BIOCHEMISTRY Krishnan, S., Collazo, E., Ortiz-Tello, P. A., Trievel, R. C. 2012; 420 (1): 48-53

    Abstract

    Jumonji C (JmjC) lysine demethylases (KDMs) are Fe(II)-dependent hydroxylases that catalyze the oxidative demethylation of methyllysine residues in histones and nonhistone proteins. These enzymes play vital roles in regulating cellular processes such as gene expression, cell cycle progression, and stem cell self-renewal and differentiation. Despite their biological importance, recombinant forms of JmjC KDMs generally display low enzymatic activity and have remained challenging to isolate in a highly active form. Here we present a simple affinity purification scheme for Strep(II)-tagged JmjC KDMs that minimizes contamination by transition state metal ions, yielding highly active and pure enzyme. We also describe an optimized continuous fluorescent assay for KDMs that detects formaldehyde production during demethylation via a coupled reaction using formaldehyde dehydrogenase. Purification and kinetic analysis of the human KDMs JMJD2A and JMJD2D using these methods yielded activities substantially higher than those previously reported for these enzymes, which are comparable to that of the flavin-dependent KDM LSD1. In addition, we show that JMJD2A exhibited a lower catalytic efficiency toward a histone peptide bearing a chemically installed trimethyllysine analog compared with a bona fide trimethylated substrate. The methodology described here is broadly applicable to other JmjC KDMs, facilitating their biochemical characterization and high-throughput screening applications.

    View details for DOI 10.1016/j.ab.2011.08.034

    View details for Web of Science ID 000296487600008

    View details for PubMedID 21925481

  • Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase NATURE STRUCTURAL & MOLECULAR BIOLOGY Couture, J., Collazo, E., Ortiz-Tello, P. A., Brunzelle, J. S., Trievel, R. C. 2007; 14 (8): 689-695

    Abstract

    JMJD2A is a JmjC histone demethylase (HDM) that catalyzes the demethylation of di- and trimethylated Lys9 and Lys36 in histone H3 (H3K9me2/3 and H3K36me2/3). Here we present the crystal structures of the JMJD2A catalytic domain in complex with H3K9me3, H3K36me2 and H3K36me3 peptides. The structures reveal that histone substrates are recognized through a network of backbone hydrogen bonds and hydrophobic interactions that deposit the trimethyllysine into the active site. The trimethylated epsilon-ammonium cation is coordinated within a methylammonium-binding pocket through carbon-oxygen (CH...O) hydrogen bonds that position one of the zeta-methyl groups adjacent to the Fe(II) center for hydroxylation and demethylation. Mutations of the residues comprising this pocket abrogate demethylation by JMJD2A, with the exception of an S288A substitution, which augments activity, particularly toward H3K9me2. We propose that this residue modulates the methylation-state specificities of JMJD2 enzymes and other trimethyllysine-specific JmjC HDMs.

    View details for DOI 10.1038/nsmb1273

    View details for Web of Science ID 000248555400005

    View details for PubMedID 17589523

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