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Timothy D. O'Connor, PhD

Academic Title:

Associate Professor

Primary Appointment:

Medicine

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 such as Hispanic Americans, African Americans, and the Old Order Amish.

Research/Clinical Keywords

Human Evolutionary Genetics, Computational Biology, Next-Generation Sequence Analysis,Genotype/Phenotype Architecture

Highlighted Publications

Tennessen JA*, Bigham AW*, O'Connor TD*, Fu W, Kenny EE, Gravel S, McGee S, Do R, Liu X, Jun G, Kang HM, Jordan D, Leal SM, Gabriel S, Rieder MJ, Abecasis G, Altshuler D, Nickerson DA, Boerwinkle E, Sunyaev S, Bustamante CD, Bamshad MJ, Akey JM. Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science. 2012 Jul 6;337(6090):64-9. PubMed PMID: 22604720

O'Connor TD, Fu W, Mychaleckyj JC, Logsdon B, Auer P, Carlson CS, Leal SM, Smith JD, Rieder MJ, Bamshad MJ, Nickerson DA, Akey JM. Rare variation facilitates inferences of fine-scale population structure in humans. Mol Biol Evol. 2015 Mar;32(3):653-60. PubMed PMID: 25415970

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 

Kessler MD, Yerges-Armstrong L, Taub MA, Shetty AC, Maloney K, Jeng LJB, Ruczinski I, Levin AM, Williams LK, Beaty TH, Mathias RA, Barnes KC, CAAPA Consortium, O’Connor, TD. Challenges and disparities in the application of personalized genomic medicine to populations with African Ancestry. Nature Communications. 2016

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 

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.* Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program. (under review). https://www.biorxiv.org/content/10.1101/563866v1 

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. 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 

Additional Publication Citations

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 (advanced access) https://www.pnas.org/content/early/2020/01/17/1902766117

Harris, D. N., Ruczinski, I., Yanek, L. R., Becker, L. C., Becker, D. M., Guio, H., Cui, T., Chilton, F. H., Mathias, R. A., O'Connor, T. D. (2019) Evolution of Hominin Polyunsaturated Fatty Acid Metabolism: From Africa to the New World. Genome Biology and Evolution. 11(5):1417-1430.                                  https://academic.oup.com/gbe/article/11/5/1417/5426762  

Awards and Affiliations

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 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 300400 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

2019-2022         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

 

Links of Interest