Golnaz Vahedi

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Assistant Professor of Genetics
Department: Genetics

Contact information
421 Curie Boulevard
Philadelphia, PA 19104
B.Sc. (Electrical Engineering)
Sharif University of Technology, Iran, 2001.
M.Sc. (Electrical Engineering)
University of Alberta, Canada, 2005.
Ph.D. (Electrical Engineering)
Texas A&M University, Texas, 2009.
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Description of Research Expertise

In every single cell in the human body, the six feet of DNA is compacted in the micrometer space of the nucleus by wrapping around spools called nucleosomes in addition to extraordinary three-dimensional folding of DNA inside the nucleus. Tissue-specific decoding of the genetic information from this extreme compression is orchestrated by specialized proteins capable of binding DNA in a sequence-specific manner. Locally, a number of proteins called lineage-determining transcription factors can access their binding sites even if they are partially occluded by nucleosomes, recruiting chromatin-remodeling enzymes and exposing the underlying DNA. Globally, sequence-specific proteins such as CTCF act as structural regulators of spatial genome organization. Considering that every two human genomes contain more than 6 million nucleotide differences and the fact that genetics is a major determinant of susceptibility to common diseases, it is essential to understand how the packaging of DNA inside the nucleus becomes resilient or susceptible to diseases due to large numbers of sequence variation. The overarching goal of the Vahedi laboratory is to understand the molecular mechanisms through which genomic information in our immune cells is interpreted in normal development and further dissect how common genetic variation can lead to misinterpretation of the genetic material in immune mediated diseases, particularly autoimmune disorders.

The multidisciplinary nature of our laboratory allows us to exploit computational and cutting-edge experimental approaches and generate unbiased maps of genome organization in primary immune cells in humans and mice. We further follow our hypothesis-generating yet unbiased efforts with experiments dissecting the mechanisms of our predictions using genome editing in mice or cell lines which provides us with an unparalleled opportunity to rigorously define the link between genetics and chromatin organization.

Biology in the 21st century is arguably the most data-rich science of the most intricately regulated dynamical systems that any discipline has to offer. We view quantitative and computational biology as intrinsic parts of the biological discipline. Our lab has an efficient and cohesive environment for trainees with no computational backgrounds to get familiar with programming and standard genomics pipelines. Trainees with previous computational expertise will be immersed in biological problems with significant implications in human health and disease. They are able to devise novel methods generating new hypotheses which can be further tested in the wet lab using genetic approaches.

List of Rotation Projects 2020-2021.

1) Mechanistic dissection of how Tcf-1 can create accessible chromatin landscape.

2) Define the 3D genome organization associated with human type 1 diabetes.

3) Dissection of architectural stripes in mammalian genomes.

4) Understanding the effect of lentiviral integration on 3D genome organization.

Selected Publications

Fasolino, M., Schwartz, G.W., Golson, M.L., Wang, Y.J., Morgan, A., Chengyang Liu, C., Schug, J., Liu, J., Wu, M., Traum, D., Kondo, A., May, C.L., Goldman, N., Wang, W., the HPAP Consortium, Feldman, M., Moore, J.H., Japp, A.S., Betts, M.R., Faryabi, R.B., Naji, A., Kaestner, K.H., Vahedi, G.: Multiomics single-cell analysis of human pancreatic islets reveals novel cellular states in health and type 1 diabetes. bioRxiv preprint February 2021 Notes: https://www.biorxiv.org/content/10.1101/2021.01.28.428598v1.

Wang W., Fasolino M., Cattau B., Goldman N., Kong W., Frederick M., McCright S., Kiani K., Fraietta J.A., Vahedi G.: Joint Profiling of Chromatin Accessibility and CAR-T Integration Site Analysis at Population and Single-cell Levels. Proceedings of National Academy of Sciences 117(10): 5442-5452, March 2020.

Fasolino M., Goldman N., Wang W., Cattau B., Zhou Y., Petrovic J., Link V.M., Cote A., Chandra A., Silverman M., Joyce E.F., Little S.C., the HPAP Consortium, Kaestner K.H., Naji A., Raj A., Henao-Mejia J., Faryabi R.B., and Vahedi G.: Genetic Variation in Type 1 Diabetes Reconfigure the 3D Chromatin Organization of T Cells. Immunity. Cell Press, 52(2): 257-274, February 2020 Notes: Featured on journal's cover. Highlighted on Spotlight in Trends Immunology.

Schwartz G.W., Zhou Y., Petrovic J., Fasolino M., Xu L., Pear W.S., Vahedi G., Faryabi R.B.: TooManyCells identifies and visualizes relationships of single-cell clades. Nature Methods 17(4): 405-413, April 2020.

Petrovic J., Zhou Y., Fasolino M., Goldma N., Schwartz G., Mumbach M., Nguyen S., Rome K., Sela Y., Zapataro Z., Blacklow S., Kruhlak M., Aster J., Shi J., Joyce E., Little S., Vahedi G., Pear W.S., Faryabi R.B.: Oncogenic Notch promotes long-range regulatory interactions within hyperconnected 3D cliques. Molecular Cell. Cell Press, 73(6): 1174-1190, March 2019.

Cai S, Georgakilas G, Johnson JL, Vahedi G: A cosine similarity-based method to infer variability of chromatin accessibility at the single-cell level. Frontiers in Genetics Page: 9:319, August 2018.

Johnson J.L., Georgakilas G., Petrovic J., Kurachi M., Cai S., Harly C., Pear W.S., Bhandoola A., Wherry E.J., Vahedi G.: Lineage-determining transcription factor TCF-1 initiates the epigenetic identity of T cells. Immunity. Cell Press, 48(2): 243-257, February 2018 Notes: Featured on journal's cover and received a News and Views. Cited > 74

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 354(6316), December 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 520(7548): 558-62, April 2015.

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, November 2012.

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Last updated: 02/08/2021
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