I am an Assistant Professor of Internal Medicine and Cancer Biology. The long-term goal of my research is to understand how altered hematopoiesis resulting from somatic mutations and/or epigenetic dysregulation impacts both malignant and non-malignant disease. During my PhD training at The University of Chicago, I worked with Dr. Tao Pan to investigate how the transcriptional process impacts in vivo RNA folding. After graduate school, I completed my residency in internal medicine and fellowship in hematology/oncology at Washington University in St. Louis. I performed my post-doctoral research with Dr. Daniel Link, studying how aging-associated somatic mutations impact the behavior of hematopoietic stem cells (HSCs) under cellular stress. One of our seminal findings was that HSCs harboring aging-associated TP53 mutations gain a competitive fitness advantage under the selective pressure of cytotoxic therapy, allowing them to clonally expand and potentially progress to therapy-related AML/MDS. Since starting my own independent research program at the University of Michigan, I have continued to investigate how somatic mutations impact hematopoiesis and how mutant hematopoietic populations impact human health. Clinically, I primarily treat patients with hematologic malignancies on the inpatient leukemia and bone marrow transplant wards.
Hematopoietic stem cells (HSCs) acquire somatic mutations with age. Some of these mutations provide HSCs with a competitive fitness advantage, allowing them to clonally expand (termed clonal hematopoiesis). Patients with clonal hematopoiesis are at increased risk for the future development of a hematologic malignancy. These patients also have an increased risk of suffering morbidity and mortality from non-hematologic diseases such as cardiovascular disease. The mutant clone is hypothesized to directly contribute towards these adverse clinical outcomes. We are interested in investigating the mechanisms through which expanded hematopoietic clones carrying certain mutations progress towards hematologic malignancy and/or interact with other aging-related disorders to induce end-organ disease. To better understand these mechanisms, we are utilizing multiple orthogonal approaches including mouse models, in vitro cell culture systems, and the analysis of patient samples. Understanding the biology of clonally expanded HSCs with aging-acquired mutations will be an area of increasing clinical significance with the currently aging population.
Research Opportunities for Rotating Students
Some ongoing projects in the Wong lab include:
1) Role of SRCAP in normal and malignant hematopoiesis
2) Impact of mutant hematopoietic populations in potentiating end-organ disease