Golnaz Vahedi, Ph.D.

Golnaz Vahedi, Ph.D.

Assistant Professor of Genetics, Member of Institute for Immunology

Lab Website
http://vahedilab.github.io/LabSite/

Faculty Website
https://www.med.upenn.edu/apps/faculty/index.php/g20001881/p8837265

Contact Information
310 Biomedical Research Building II/III
421 Curie Boulevard
Philadelphia, PA 19104
Office: 215-898-8439
Email: vahedi@mail.med.upenn.edu

Research Interest

The Vahedi laboratory is multidisciplinary, integrating computational and experimental approaches to develop a single to collective cell understanding of gene regulation in immune cells in health and disease.

We exploit the epigenomics mapping of immune cells to understand the biological circuits that underlie immune responses and uncover the molecular basis of major inherited diseases mediated by these cells. Immune-mediated disorders such as psoriasis and type 1 diabetes result from a complex interplay of genetic and environmental factors. By mapping the epigenomic alterations associated with immune-mediated diseases, we aim to further our understanding of the role of environment in triggering autoimmunity.

Information encoded in DNA is interpreted, modified, and propagated as chromatin. The diversity of inputs encountered by immune cells demands a matching capacity for transcriptional outcomes provided by the combinatorial and dynamic nature of epigenetic processes. Advances in genome editing and genome-wide analyses have revealed unprecedented complexity of chromatin pathways involved in the immune response, offering explanations to long-standing questions and presenting new challenges.

We blend epigenomics, human genetics, immunology, and computational biology to pursue a new understanding of human immunology. We generate genome-wide maps of chromatin in relevant immune cells mostly T cells. We are interested in regulators of T cell development and also T cell engagement in autoimmune disorders such as psoriasis and type 1 diabetes. We use population-based assays with strong signal-to-noise ratios such as ChIP-seq, ATAC-seq, and RNA-seq in addition to cutting-edge single-cell assays such as single-cell (sc)ATAC-seq and scRNA-seq. As a result of our computational expertise, we also harvest the vast troves of big data that immunologists and other researchers are pouring into public repositories. Our data integrations rely on available computational pipelines. Furthermore, we develop novel computational techniques to fully understand the complexity of multidimensional epigenomics datasets in T cells.

Contribution to Science

We have demonstrated for the first time that the epigenome of differentiated CD4 T cells is highly dynamic and extended these findings to human genetics to further our understanding of the epigenetic control in autoimmunity.

Johnson J.L. and Vahedi G.: Epigenome: a dynamic vehicle for transmitting and recording cytokine signalling. CSHL Perspectives, Cold Spring Harbor Laboratory Press 2017.

Pauken, K. E., Sammons, M. A., Odorizzi, P. M., Manne, S., Godec, J., Khan, O., Drake, A. M., Chen, Z., Sen, D., Kurachi, M., Barnitz, R. A., Bartman, C., Bengsch, B., Huang, A. C., Schenkel, J. M., Vahedi, G., Haining, W. N., Berger, S. L., Wherry, E. J.: Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Science 2016.

Richard AC, Peters JE, Lee JC, Vahedi G, Schäffer AA, Siegel RM, Lyons PA, Smith KG.: Targeted genomic analysis reveals widespread autoimmune disease association with regulatory variants in the TNF superfamily cytokine signalling network. Genome Medicine 76(8), July 2016.

Johnson, J. L., Vahedi, G.: Exploiting Chromatin Biology to Understand Immunology. Methods Enzymol 574: 365-83, 2016.

Vahedi, G., Kanno, Y., Furumoto, Y., Jiang, K., Parker, S. C., Erdos, M. R., Davis, S. R., Roychoudhuri, R., Restifo, N. P., Gadina, M., Tang, Z., Ruan, Y., Collins, F. S., Sartorelli, V., O’Shea, J. J.: Super-enhancers delineate disease-associated regulatory nodes in T cells. Nature April 2015.

Vahedi, G., Kanno, Y., Sartorelli, V., O’Shea, J. J.: Transcription factors and CD4 T cells seeking identity: masters, minions, setters and spikers. Immunology 139(3): 294-8, 2013.

Vahedi, G., C. Poholek A, Hand, T. W., Laurence, A., Kanno, Y., O’Shea, J. J., Hirahara, K.: Helper T-cell identity and evolution of differential transcriptomes and epigenomes. Immunol Rev 252(1): 24-40, 2013.

Roychoudhuri, R., Hirahara, K., Mousavi, K., Clever, D., Klebanoff, C. A., Bonelli, M., Sciume, G., Zare, H., Vahedi, G., … , O’Shea, J. J., Restifo, N. P.: BACH2 represses effector programs to stabilize T(reg)-mediated immune homeostasis. Nature 498(7455): 506-10, 2013.

Vahedi, G., Takahashi, H., Nakayamada, S., Sun, H. W., Sartorelli, V., Kanno, Y., O’Shea, J. J.: STATs shape the active enhancer landscape of T cell populations. Cell 151(5): 981-93, 2012.

Vahedi, G., Faryabi, B., Chamberland, J. F., Datta, A., Dougherty, E. R.: Intervention in gene regulatory networks via a stationary mean-first-passage-time control policy. IEEE Trans Biomed Eng 55(10): 2319-31, 2008.