Email

marco.gallo@bcm.edu

Positions

Associate Professor

Department of Pediatrics
Section of Hematology-Oncology
Baylor College of Medicine
Houston, TX

Member

Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, TX

Education

PhD from University of British Columbia

Vancouver, BC Canada

BSc from Simon Fraser University

Burnaby, BC Canada

Postdoctoral Fellowship at Hospital for Sick Children

Toronto, ON Canada

Professional Statement

The goal of Dr. Marco Gallo's research is to discover the mechanisms by which the epigenome and non-coding genome drive tumorigenesis in pediatric and adult brain tumors. His laboratory consists of an integrated team of bioinformaticians and wet lab scientists who investigate the function of epigenetic and chromatin factors and 3D genome architecture in programming stem-like states in brain tumors.

Among other contributions, his research has shed light on the intratumoral organization and evolution of genetic subclones in pediatric high-grade gliomas (Cancer Research, 2019), the link between 3D genome organization and expression of targetable antigens in adult glioblastoma (Genome Research, 2019), how subclonalgenetics influences chromatin organization (Science Advances, 2021) and identified chromatin factors that promote cell state transitions (Nature Communications, 2023). Recently, the Gallo lab has discovered new 3D genome structures in PFA ependymoma, a pediatric brain tumor, called TULIPs (Cell, 2024).

He has received awards from provincial, national and international organizations, including: the Institute of Cancer Research at the Canadian Institutes of Health Research (CIHR), the Society for Neuro-Oncology and Stand Up To Cancer.

Websites

Selected Publications

• Nikolic A, ... Gallo M "macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma." Nature Communications. 2023;14:3062. Pubmed PMID: 37244935
• Nikolic A, ... Gallo M "Copy-scAT: Deconvoluting single-cell chromatin accessibility of genetic subclones in cancer." Science Advances. 2021;7:abg6045. Pubmed PMID: 34644115
• Gallo M, ... Dirks PB "MLL5 orchestrates a cancer self-renewal state by repressing the histone variant H3.3 and globally reorganizing chromatin." Cancer Cell. 2015;28:715-729. Pubmed PMID: 26626085
• Johnston MJ, ... Gallo M "TULIPs decorate the three-dimensional genome of PFA ependymoma." Cell. 2024;187:4926-4945. Pubmed PMID: 38986619

Projects

Epigenetic heterogeneity in brain tumors

Not all cells in a brain tumor are the same. For instance, some cells are resistant to therapy, whereas others are sensitive; some divide frequently and generate lots of other tumor cells, whereas others appear dormant. Recognizing that brain tumors are ecosystems composed of many different types of cells, we adopted technologies that enable genomic profiling of individual cells, including scRNA-seq and scATAC-seq. These platforms are leading to better understanding of how tumor cells interact with each other and with their microenvironment, how they escape treatment and the immune system. We are using this information to figure out ways to target tumor cells more effectively. Our wet and dry lab teams have been working together to generate single-cell -omics data from clinical specimens and our patient-derived models, perform informatics analyses to generate new hypotheses, and functionally test our predictions.

3D genome in brain tumors

The function of a cell is determined by which genes are turned on or off. As an example, neurons and astrocytes in the brain turn on different sets of genes. The genome is organized in three-dimensional (3D) space inside the nucleus to enable some genes to be turned on, while turning off other genes that are not needed in a given type of cell. Likewise, the function and behavior of tumor cells is impacted by 3D genome architecture. Our lab has deployed new techniques – including Hi-C – to reconstruct the 3D genome of brain cancer cells. These efforts are enabling us to understand the strategies used by the tumor to turn on genes that contribute to its aggressive behavior and to therapy resistance.

Preclinical studies

We use clinical samples – usually surgical tumor resections – to grow patient-specific cell lines in the lab. These cell lines allow us to model each patient’s disease, giving us a better understanding of how brain cancers behave in different patients. They also give us an opportunity to identify biological processes that are shared across patients and that could be exploited to design new treatments. These patient-derived models are used to understand how the genome and epigenome impact the function of malignant cells. We use molecular tools and genome engineering to turn off or on specific genes and then test their effect on cell fitness. We also transplant these patient-derived models in mice to explore efficacy of new molecular approaches in preclinical settings. Our preclinical models faithfully recapitulate salient features of the cancers we study and we are using them to translate our discoveries into better treatments for patients.