Federico Gaiti

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Scientist, Princess Margaret Cancer Centre

https://orcid.org/0000-0001-5111-8816
Keywords: cancer evolution, single-cell, multi-omics, epigenetics, tumour microenvironment, genotype, cellular states, plasticity, lineage tracing

Dr. Gaiti is a Scientist at the Princess Margaret Cancer Centre, University Health Network, and Assistant Professor in the Dept. of Medical Biophysics at the University of Toronto. He earned his PhD in evolutionary biology and genomics from the University of Queensland (Australia), where he focused on understanding the evolutionary origin of two major players in human gene regulation: long non-coding RNAs and chromatin marks. As a postdoctoral fellow, he joined Dr. Dan Landau’s laboratory at Weill Cornell Medicine and New York Genome Center. He studied the epigenetic determinants of cancer evolution using novel single-cell multi-omics experimental and computational approaches in blood disorders (leukemia) and brain tumors (glioma). His works has been recognized by prestigious postdoctoral fellowships and awards, including the NIH Pathway to Independence Award (K99/R00), the American Society of Hematology Scholar Award, the Lymphoma Research Foundation Postdoctoral Fellowship, and the Leukemia & Lymphoma Society Award. Dr. Gaiti is now developing and applying these single-cell multi-omics approaches to answer the fundamental question of how malignant cellular states in cancer are jointly determined by genetic and epigenetic alterations. Dr. Gaiti is committed to a career in basic cancer research with translational impact, making discoveries that would offer improved therapeutic options to directly address cancer evolution.

Our research focuses on providing novel insights into a central aspect of human biology – somatic evolution of cancer cells. Cancer progression, relapse, and resistance to therapy are the result of an evolutionary optimization process, in which genetic alterations generate diversity. This genetic diversity provides the critical substrate for malignant cells to evolve and adapt to the selective pressures provided by a therapeutic intervention. However, in addition to genetic diversity, there is a whole host of heritable layers of information, like epigenetic layers, that fuel cancer evolution. Thus, the study of cancer requires the integration of multiple heritable dimensions at the resolution of the single cell — the fundamental unit of somatic evolution.

The goal of our research program is to develop and apply computational and experimental genomics and epigenomics approaches for the study of cancer evolution and analysis of single-cell multi-omics data, empowering us to simultaneously interrogate the multi-faceted axes of diversity that drive tumor evolution. From a clinical perspective, the evolutionary plasticity of cancer cells is one of the major reasons for partial therapeutic success in oncology, emphasizing the key challenge associated with attempts at eradicating specific malignant cellular subsets. Understanding of the mechanisms underlying this evolutionary process, which contributes to greater diversity of subpopulations within the cancer, is therefore critical to discover fundamental principles in evolutionary biology and biological regulation of cancer cells and to better inform the future design and application of more effective therapeutic options.

Current efforts in the lab focus on understanding:

1. Role of non-genetic/epigenetic alterations (DNA methylation or chromatin factors) in dictating malignant cell states.

2. The phenotypic plasticity of malignant cell states.

3. The impact of cell extrinsic factors (such as tumor microenvironment) on malignant cell states.

For more information, please visit the Gaiti Lab website.

For a list of Dr. Gaiti's publications, please visit PubMed, Scopus or ORCID. 

Scientist, Princess Margaret Cancer Centre

Assistant Professor, Department of Medical Biophysics, University of Toronto