Allegra Petti, PhD
Assistant Professor of Medicine
Allegra A. Petti is an Assistant Professor in the Department of Medicine, Division of Oncology, and the McDonnell Genome Institute at Washington University School of Medicine. She is interested in the structure and function of gene regulatory networks in healthy and diseased tissues. To this end, she develops analytical approaches for the integration and interpretation of multi-dimensional genomic data, with an emphasis on single-cell RNA-sequencing (scRNA-seq) data. She applies these approaches to a variety of biologically and clinically relevant questions that are best addressed at single-cell resolution.
One current focus is to understand tumor heterogeneity and evolution in acute myeloid leukemia (AML) from the perspective of gene expression. AML (like other cancers) is a collection of genetically distinct cell populations, or subclones, derived from an ancestral cell. Subclones can differ with respect to proliferation rate, drug sensitivity, and other biological parameters that influence tumor evolution and disease progression. Although genome sequencing can be used to define and track the subclonal architecture of individual tumors, the biological basis for subclonal phenotypic variation remains poorly understood. Dr. Petti is integrating scRNA-seq, whole genome sequence (WGS), and bulk RNA-sequence data in paired presentation/relapse AML samples to better understand the biological basis of subclonal heterogeneity, and to reconstruct the gene expression changes that underlie progression from presentation to relapse.
In related work, Dr. Petti is developing strategies to identify mutations in single cells using a combination of scRNA-seq and WGS data. This should make it possible to directly link mutationally-defined subclones to specific gene expression profiles.
Dr. Petti participates in several collaborations that require the integration of multiple types of genomic data to understand: 1) tumor heterogeneity and the microenvironment in solid tumors, 2) mechanism of relapse after allogeneic transplantation for AML, 3) mechanism of decitabine response in TP53-mutated AML, and 4) transcriptional targets of Dnmt3a (which is commonly mutated in AML) in mice.