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