Allegra A. Petti, Ph.D.

Assistant Professor
Neurosurgery

Computational and Systems Biology Program
Molecular Genetics and Genomics Program
Computational and Systems Biology Program
Human and Statistical Genetics Program

  • 314-286-0263

  • allegra.petti@wustl.edu

  • We seek to understand tumor ecosystems at single-cell resolution during the development and evolution of human cancer

Research Abstract:

We seek to understand tumor ecosystems at single-cell resolution during the development and evolution of human cancer. To this end, we use computational approaches to analyze, integrate, and interpret large-scale genomic data -- with an emphasis on single-cell RNA-sequencing data and emerging genomic technologies. We participate in long-term, data-driven collaborations with clinicians and other labs at the Washington University Scool of Medicine, in which quantitative analysis is closely integrated with clinical studies and molecular biology. Areas of focus include:

Intratumoral expression heterogeneity. Virtually all tumors are genetically heterogeneous, containing subclonal populations of cells that are defined by distinct mutations. Subclones can have unique phenotypes that influence tumor evolution and disease progression, but these phenotypes are difficult to characterize, because it is often impossible to purify individual subclones. Using single-cell RNA-sequencing, however, it is possible to assay gene expression in every cell in every subclone without physically purifying the subclones. By combining this data with whole genome sequence data obtained from paired tumor/normal samples, we hope to better understand the biological differences among subclones.

Tumor evolution. We are studying the biological basis of relapse –-and its relationship to intratumoral expression heterogeneity —--by combining scRNA-seq and whole genome sequencing of tumor samples obtained at presentation and relapse.

Spatial, genetic, epigenetic, and immunological heterogeneity in solid tumors. By integrating exome sequencing, scRNA-seq, and single cell T-cell receptor sequencing, we are building multidimensional portraits of solid tumors aimed at understanding the relationships among transcriptional heterogeneity, genetic heterogeneity, neoantigens, infiltrating immune cells, and clonotypic diversity of T-cell receptors.

Selected Publications:

Petti AA*, Williams SR*, Miller CA, Fiddes IT, Srivatsan SN, Chen DY, Fronick CC, Fulton RS, Church DM, and Ley TJ. A general approach for detecting expressed mutations in AML cells using single cell RNA-sequencing. Nature Commun. 2019; 10(1):3660.1-3660.16.

Christopher MJ*, Petti AA*, Rettig MP*, Miller CA, Chendamarai E, Duncavage EJ, Klco JM, Helton NM, O’Laughlin M, Fronick, CC, Fulton RS, Wilson RK, Wartman LD, Welch JS, Heath SE, Baty JD, Payton JE, Graubert TA, Link DC, Walter MJ, Westervelt P, Ley TJ, and DiPersio, JF. Immune Escape of Relapsed AML Cells after Allogeneic Transplantation. New England Journal of Medicine 2018; 379(24):2330-2341.

Zhu L, Cheng G, Ye D, Nazeri A, Yue Y, Liu W, Wang X, Dunn GP, Petti AA, Leuthardt EC, Chen H. Focused Ultrasound-enabled Brain Tumor Liquid Biopsy. Sci Rep. 2018; 8(1):6553-6561.

Cole CB*, Russler-Germain DA*, Ketkar S*, Verdoni AM, Smith AM, Venezia C, Helton NM, Guo M, Klco JM, O’Laughlin S, Fronick C, Fulton R, Chang GS, Petti AA, Miller CA, and Ley TJ. Dnmt3A haploinsufficiency predisposes hematopoietic cells to myeloid malignancies. J. Clinical Investigation 2017; 127(10):3657-3674.

Welch JS, Petti AA, Ley TJ. Decitabine in TP53-Mutated AML. New Engl J Med. 2017; 376(8):797-798.

Zhang X, Kim S, Hundal J, Herndon JM, Li S, Petti AA, Soysal SD, Li L, McLellan MD, Hoog J, Primeau T, Myers N, Vickery TL, Sturmoski M, Hagemann IS, Miller CA, Ellis MJ, Mardis ER, Hansen T, Fleming TP, Goedegebuure SP, Gillanders WE. Breast Cancer Neoantigens Can Induce CD8+T-Cell Responses and Antitumor Immunity. Cancer Immunol Res. 2017; 5(7):516-523.

Duncavage EJ*, Uy GL*, Petti AA, Miller CA, Lee Y-S, Tandon B, Gao F, Fronick CC, O’Laughlin M, Fulton RS, Wilson RK, Jacoby MA, Cashen AF, Wartman LD, Walter MJ, Westervelt P, Link DC, DiPersio JF, Ley TJ, Welch JS. Mutational landscape and response is conserved in the peripheral blood of AML and MDS patients during decitabine therapy. Blood 2017; 129(10):1397-1401.

* Denotes equal contribution

Last Updated: 6/15/2021 10:17:16 AM

Back To Top

Follow us: