Update Your ProfileAcademic Title:
Associate Professor
Primary Appointment:
Medicine
Administrative Title:
Co-Director for the Program in Health Equity and Population Health (HEPH)
Location:
Health Sciences Facility III, 670 West Baltimore St, Baltimore 21201
Phone (Primary):
410-706-6784
Education and Training
2001-2007: B.S. Bioinformatics, Brigham Young University
2007-2011: Ph.D. Evolutionary Genetics, University of Cambridge (Dr. Nicholas I. Mundy)
2007-2011: Gates Cambridge Scholar
2010-2013: Senior Research Fellow, Dept. of Genome Science, University of Washington (Dr. Joshua Akey)
Biosketch
My laboratory explores the effects of evolution and population structure on the genomic architecture of disease and other phenotypes. One of the biggest questions of modern genetics and evolution is to understand the complex connection between genes, environment, and phenotype. We want to understand the origin of phenotypic diversity. We believe this will require the integration of many data types, scientific disciplines, and a heavy reliance on evolutionary theory. As we move forward in developing theories and addressing this important problem it will be important to combine evolutionary genetics and systems biology. My lab has a track record of developing new algorithms and statistics to interdisciplinary biological problems as well as the use of large multifaceted data sets, particularly the output of next-generation sequencing. We are especially interested in the recent evolution of New World populations.
Research/Clinical Keywords
Human Evolutionary Genetics, Computational Biology, Genotype/Phenotype Architecture, Genetic Epidemiology, Latin American Genetics
Highlighted Publications
Kessler, M. D., Bateman, N. W., Conrads, T. P., Maxwell, G. L., Dunning Hotopp, J. C., O’Connor, T. D. (2019) Ancestral characterization of 1018 cancer cell lines highlights disparities, and reveals gene expression and mutational differences. Cancer. 125(12):2076-2088. https://www.ncbi.nlm.nih.gov/pubmed/30865299
Harris, D. N., Song, W., Shetty, A. C., Levano, K. S., Cáceres, O., Padilla, C., Borda, V., Tarazona, D., Trujillo, O., Sanchez, C., Kessler, M. D., Galarza, M., Capristano, S., Montejo, H., Flores-Villanueva, P. O., Tarazona-Santos, E., O'Connor, T. D.*, Guio, H.* (2018) Evolutionary genomic dynamics of Peruvians before, during, and after the Inca Empire. Proceedings of the National Academy of Science USA. 115(28):E6526-E6535. 29946025
Shetty, A. C., Jacob, C. G., Huang, F., Li, Y., Agrawal, S., Saunders, D. L., Lon, C., Fukuda, M. M., Ringwald, P., Ashley, E. A., Han, K. T., Hlaing, T. M., Nyunt, M. M., Silva, J. C., Stewart, K. E., Plowe, C. V., O'Connor, T. D.*, Takala-Harrison, S.*, and Artemisinin Resistance Confirmation, Characterization, and Containment (ARC3), Artemisinin Resistance Containment and Elimination (ARCE), Tracking Resistance to Artemisinin Collaboration (TRAC), and MalariaGEN Plasmodium falciparum Community Project. (2019) Genomic structure and diversity of Plasmodium falciparum in Southeast Asia reveal recent parasite migration patterns. Nature Communications. 10:2665. https://www.nature.com/articles/s41467-019-10121-3
Harris, D. N., Kessler, M. D., Shetty, A. C., Weeks, D. E., Minster, R., Browning, S., Cochrane, E. E., Deka, R., Hawley, N. L., Reupena, M. S., Naseri, T., Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Population Genetics Working Group, McGarvey, S. T., O’Connor, T. D. (2020) Evolutionary History of Modern Samoans PNAS. 117 (17) 9458-9465. https://www.pnas.org/content/117/17/9458
Kessler, M. D., Loesch, D. P., Perry, J., Heard-Costa, N. L., Cade, B., Wang, H., Daya, M., Ziniti, J., Datta, S., Celedón , J. C., Soto-Quiros, M. E., Avila, L., Weiss, S. T., Barnes, K., Redline, S., Vasan, R. S., Johnson, A. D., Mathias, R. A., Hernandez, R., Wilson, J. G., Nickerson, D. A., Abecasis, G., Browning, S., Zoellner, S., O’Connell, J., Mitchell, B., TOPMed, Consortium, TOPMed Population Genetics Working Group, O’Connor, T. D. (2020) de novo mutations across 1,465 ancestrally diverse genomes reveal novel mutational insights and reductions in the Amish founder population. PNAS. 117 (5) 2560-2569. https://www.pnas.org/content/early/2020/01/17/1902766117
Taliun, D.*, Harris, D. N.*, Kessler, M. D.*, Carlson, J.*, Szpiech, Z. A.*, Torres, R.*, Gagliano Taliun, S. A.*, Corvelo, A.*, Gogarten, S. M., Kang, H. Min, Pitsillides, A. N., LeFaive, J., Lee, S.-B., Tian, X., Browning, B. L., Das, S., Clarke, W. E., Emde, A.-Katrin, Loesch, D. P., Shetty, A. C., Blackwell, T. W., Wong, Q., Aguet, F.çois, Albert, C., Alonso, A., Ardlie, K. G., Aslibekyan, S., Auer, P. L., Barnard, J., Barr, R. Graham, Becker, L. C., Beer, R. L., Benjamin, E. J., Bielak, L. F., Blangero, J., Boehnke, M., Bowden, D. W., Brody, J. A., Burchard, E. G., Cade, B. E., Casella, J. F., Chalazan, B., Chen, Y.-D. I., Cho, M., Choi, S. Hoan, Chung, M. K., Clish, C. B., Correa, A., Curran, J. E., Darbar, D., Daya, M., Andrade, M. de, DeMeo, D. L., Dutcher, S., Ellinor, P. T., Emery, L. S., Forer, L., Fornage, M., Franceschini, N., Fuchsberger, C., Fullerton, S. M., Germer, S., Gottlieb, D. J., Guo, X., Hall, M. E., He, J., Heard-Costa, N. L., Heckbert, S. R., Irvin, M. R., Johnson, A. D., Kardia, S. L.R., Kelly, T., Kelly, S., Kiel, D. P., Klemmer, R., Kooperberg, C., Köttgen, A., Lange, L. A., Lasky-Su, J., Levy, D., Lin, X., Lin, K.-Han, Liu, C., Lori, G., Lubitz, S. A., Lunetta, K. L., Mak, A. C.Y., Manichaikul, A., Manning, A. K., Mathias, R. A., McGarvey, S. T., Meigs, J. B., Mikulla, J. L., Minear, M. A., Mitchell, B., Montasser, M. E., Montgomery, C., Morrison, A. C., Murabito, J. M., Natarajan, P., Nelson, S. C., North, K. E., O'Connell, J. R., Palmer, N. D., Pankratz, N., Peloso, G. M., Peyser, P. A., Psaty, B. M., Rao, D.C., Redline, S., Reiner, A. P., Roden, D., Rotter, J. I., Ruczinski, I., Sarnowski, C.é, Schoenherr, S., Seo, J.-Sun, Seshadri, S., Shoemaker, M. Benjamin, Smith, A. V., Smith, N. L., Smith, J. A., Sotoodehnia, N., Stilp, A. M., Tang, W., Taylor, K. D., Thornton, T. A., Tracy, R. P., Vasan, R. S., Viaud-Martinez, K., Vrieze, S., Weeks, D. E, Weir, B. S., Weiss, S. T., Weng, L. Chen, Willer, C. J., Zhao, X., Arnett, D. K., Ashley-Koch, A. E., Barnes, K. C., Boerwinkle, E., Gabriel, S., Gibbs, R., Rice, K. M., Rich, S. S., Silverman, E., Qasba, P., Gan, W., Trans-Omics for Precision Medicine (TOPMed) Program, TOPMed Population Genetics Working Group, Papanicolaou, G. J., Nickerson, D. A., Browning, S. R., Zody, M. C., Zöllner, S., Wilson, J. G., Cupples, L. A., Laurie, C. C.*, Jaquish, C. E.*, Hernandez, R. D.*, O'Connor, T. D.*, Abecasis, G. R.* (2021) Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program. Nature. 590:290–299. https://www.nature.com/articles/s41586-021-03205-y
Awards and Affiliations
2021 Epidemiology and Human Genetics Program, and Gerontology Program, Faculty Mentoring Award.
2019 Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition Teacher of the Year Award.
2017 Dr. Patricia Sokolove Outstanding Mentor Award, University of Maryland Baltimore System Graduate School, encompassing School of Dentistry, School of Medicine, School of Pharmacy, School of Social Work, and School of Nursing.
Grants and Contracts
1 R01 AI145852 (Harrison, O’Connor) 03/01/2020 – 02/28/2025
NIH/NIAID $499,998
Genomic and geospatial analyses of malaria parasite migration to inform elimination
In this project, we will look at the Cambodia/Thai border using both genetic models of relatedness within P. falciparum and P. vivax as well as integrating geospatial sampling and travel surveys to get a contemporaneous model of migration in this region.
Role: Multi-Principal Investigator
1 R35 HG010692-01 (O’Connor) 09/01/2019 – 06/30/2024
NIH/NIGMS $299,713
Rapid Evolution of Genomic Architecture and Multi-omics Traits
We will test the hypothesis that multi-omics traits evolve quickly using a combination of large genomic data sets and matched multi-omics profiles through the TOPMed consortium. To accomplish this, we will integrate rare variants and segments that are identical by descent into better epidemiological models. Further, we will develop an evolutionary systems biology framework to model change in multi-omics profiles over the last 100 generations.
Role: Principal Investigator
GYN-COE (O’Connor) 03/01/2019 – 02/29/2020
Henry M. Jackson Foundation $49,301
Gynecological Cancer Center of Excellence
We will perform admixture analyses for the exome sequencing from a large national collaboration of endometrial cancer studies. We will have approximately 300‐400 tumor/normal exomes completed towards the end of 2019 paired with proteomic data of tumors and incrementally growing sets of WGS and other data from additional projects. This is government appropriated funding, budgeted yearly, with the expectation that this consortium will continue for multiple years.
Role: Site Principle Investigator
Dean’s Challenge Award (O’Connor, Pollin, Kittner) 07/01/2018 – 06/30/2020
UM-SOM $85,000
Patient ENgaged Genomic Understanding and INterpretation (PENGUIN): Familial Mediterranean Fever as a Case Study
This project will explore a novel solution, the PENGUIN model, to the dual problems of limited access to genetic information/services on one hand, and harmful consequences of misinformation arising from some direct to consumer genetic testing uses on the other. Patients who may have an identifiable genetic cause to their disease undergo whole exome sequencing in a CLIA/CAP accredited laboratory. They then participate in a workshop conducted by an interdisciplinary team comprising health and research professionals in the areas of genetic counseling, clinical genetics, bioinformatics, and relevant disease areas along with patient advocates.
Role: Multi-Principal Investigator
In the News
Professional Activity
2019-2021 Program Committee for the American Society of Human Genetics (ASHG)
2016 – present Ad hoc reviewer for National Institutes of Health study sections
2015 – present Co-convener Population Genetics Working Group Trans-Omics for Precision Medicine (TOPMed) Project (www.nhlbiwgs.org)
2015 – present TOPMed Papers and Publications committee
2015 Reviewer for the Population and Evolutionary Genetics section of the ASHG meeting