Position Description

We invite applications for a postdoctoral fellow position in the Santagata Lab at Harvard Medical School in Boston, Massachusetts, focused on the Gray Foundation BRCA Pre-Cancer Atlas initiative.

This project is centered on understanding the earliest stages of high-grade serous ovarian cancer (HGSOC) by integrating spatial multi-omic profiling with computational analysis to define how precancerous lesions evolve into invasive disease. The work aims to move beyond descriptive atlases toward identifying the biological states and transitions that determine when a lesion becomes dangerous and where intervention is possible.

Recent work from this program includes two key studies in Cancer Discovery that define the molecular and spatial progression of ovarian cancer precursors. One study used multimodal spatial profiling to reveal a transition from immune surveillance to immune suppression during progression from early lesions to cancer (Kader et al., Cancer Discovery 2025). A second study developed ORION-FISH, a method that integrates chromosomal copy-number alterations with protein-defined cell states in intact tissue, linking early genomic changes (e.g., MYC, CCNE1 gains) to local immune microenvironments at single-cell resolution. Together, these studies establish a framework for understanding how genomic, immune, and microenvironmental factors interact during the earliest phases of tumor evolution.

The successful candidate will work with Dr. Santagata and collaborators across Harvard Medical School, Dana-Farber Cancer Institute, and the University of Pennsylvania to define the next phase of the Pre-Cancer Atlas and translate its insights into clinically actionable strategies. Ongoing efforts focus on building an integrated, multi-modal map of early ovarian cancer evolution using CyCIF, ORION, GeoMx, and Xenium; establishing direct links between genomic alterations, epithelial cell states, and immune microenvironments; and identifying the biological transitions that mark the shift from benign or indolent lesions to high-risk, intervention-relevant states.

A central goal of the program is to move beyond cataloging features to discovering the rules that govern progression and vulnerability - including how early chromosomal instability, immune remodeling, and metabolic stress interact within intact tissue architecture. These insights are being leveraged to develop image-based and molecular biomarkers for early detection, risk stratification, and therapeutic interception, with direct paths toward clinical translation.

The fellow will have the opportunity to lead independent, high-impact projects within this framework, including defining new biological axes of progression, developing integrative computational models of early disease states, and contributing to the design of next-generation diagnostic and intervention strategies. In addition to conducting research, the fellow will be expected to contribute to grant and manuscript writing, mentor junior trainees, and participate in a highly collaborative, interdisciplinary research environment.