734-615-2589

Applications:
Bioinformatics, Biological Sciences, Genetics, Genomics
Methodologies:
Longitudinal Data Analysis, Statistics
Relevant Projects:

Hematopoietic stem cells (HSCs) acquire somatic mutations with age, resulting in a genetically heterogeneous population with each HSC possessing its own unique set of mutations. These HSCs compete against each other under the influence of cellular stress (e.g. inflammation, cytotoxic therapy, etc.) with HSCs carrying distinct mutations gaining a competitive advantage under specific conditions. Expanded mutant clones may have a significant impact on human health with some clones more likely to evolve into hematologic malignancies and others impacting non-hematologic aging-associated disorders such as cardiovascular disease. Through the next generation sequencing of patient cohorts, we are interested in determining how different cellular stressors impact the expansion of clones carrying specific mutations and how these mutant clones influence the pathogenesis and progression of aging-associated human disorders. We will then model these mutations in the laboratory to determine the molecular mechanisms underlying these interactions. Using this approach, we hope to identify those individuals at highest risk of developing certain diseases (e.g. AML, cardiovascular disease) and potentially abrogating the development of such disorders.

The hematopoietic population becomes increasingly genetically heterogeneous with age. Under certain cellular stressors (e.g. cytotoxic therapy), hematopoietic stem cells carrying specific mutations can clonally expand. Some of these expanded hematopoietic populations can impact human health (e.g. through the development of hematologic malignancy). By understanding the interaction of cellular stress and mutant clonal expansion, the potential exists to prevent the expansion of poor prognosis hematopoietic clones and/or diminish the impact of such clones on human disease in those cases where expansion has already occurred.

 

 

 

 

 

 

 

 

 


Terrence Wong

Assistant Professor

Department of Internal Medicine; Division of Hematology and Oncology

Terrence Wong is a Assistant Professor of Internal Medicine and Cancer Biology. The long-term goal of his research is to understand how altered hematopoiesis resulting from somatic mutations and/or epigenetic dysregulation impacts both malignant and non-malignant disease. During his PhD training at The University of Chicago, he worked with Dr. Tao Pan to investigate how the transcriptional process impacts in vivo RNA folding. After graduate school, he completed his residency in internal medicine and fellowship in hematology/oncology at Washington University in St. Louis. He 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 their 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 his own independent research program at the University of Michigan, he has continued to investigate how somatic mutations impact hematopoiesis and how mutant hematopoietic populations impact human health. Clinically, he primarily treats patients with hematologic malignancies on the inpatient leukemia and bone marrow transplant wards.