Terrence Wong, MD, PhD

University of Michigan

Titles + affiliations

Assistant Professor of Internal Medicine
University of Michigan Medical School


The Role of SRCAP in Hematopoiesis and Leukemogenesis


Mutations in SRCAP have recently been identified in hematologic disorders such as AML, suggesting the importance of this gene in leukemogenesis. SRCAP is responsible for the deposition of H2A.Z into chromosomes, which remains a poorly understood mechanism of epigenetic regulation. We used a novel mouse model of Srcap loss to determine that it is essential for normal hematopoiesis including stem cell function. Hematopoietic cells lacking this gene had upregulation of p53, a marker of cellular stress. Based on this data and previously identified roles of SRCAP and H2A.Z in the response to DNA damage, we hypothesize that SRCAP is essential for the maintenance of genomic integrity and that disruption of SRCAP function may promote the development of leukemia. Using a mouse model of Srcap loss, mouse leukemia models, and human cell lines, we will determine whether loss of Srcap cooperates with other mutations identified in AML such as AML1-ETO to promote leukemogenesis and assess the impact of Srcap loss on genomic integrity in both non-malignant hematopoietic and leukemic populations. We will then investigate how SRCAP loss impacts H2A.Z occupancy and whether this correlates with sites of genomic damage, altered genome accessibility, or gene expression changes. These studies will significantly increase our understanding of H2A.Z biology. They will also provide insights on how leukemic clones maintain genomic integrity, which may reveal new therapeutic vulnerabilities in AML.


Leukemia Research Foundation grant
$100K awarded in 2022

Disease focus
Acute myeloid leukemia (AML)

Research focus
Causes/risk factors (genetics)