Uma Arora
Research Fellow, Broad Institute
3 active projects
myeloid-disease-burden
Scientific Questions Being Studied
Exploration of genetic determinants and predisposition to myeloid disease. What genetic landscape exists for these collection of diseases? Does this landscape differ in currently under-represented groups in genetics? How do blood traits apply in this context?
Project Purpose(s)
- Disease Focused Research (myeloid disease and blood traits)
- Ancestry
Scientific Approaches
Phenotype, Array, Exome, Genome sequences Methods: association testing, finemapping, and other related tools/methods
Anticipated Findings
We expect this work to contribute to the understanding of HSC (human hematopoietic stem cell) biology and how it is altered in these disease states.
Demographic Categories of Interest
- Race / Ethnicity
Data Set Used
Controlled TierResearch Team
Owner:
Duplicate of Hereditary blood disorders
Scientific Questions Being Studied
The genetic etiology of many hereditary blood disorders is not comprehensively known. Furthermore, when the genes are known, there is often variable expressivity in terms of phenotypic manifestation of the disease. We want to explore the interaction between rare disease-causing genetic variants and common genetic variants governing related traits and how they impact phenotypic manifestation of the disease. This is important to gain a comprehensive understanding of the effects of genetic background on disease incidence and susceptibility. This information is valuable when making decisions about using genetic testing to diagnose diseases or for genetically informed personalized therapies.
Project Purpose(s)
- Ancestry
Scientific Approaches
We are going to use GWAS summary statistics from blood cell traits to calculate a polygenic score for individuals for each blood cell trait. We are also going to perform RVAS analyses for blood diseases. We will then perform additional statistical tests and analyses to explore the relationship between rare variants and common variants involved in disease and blood cell traits.
Anticipated Findings
We anticipate understanding the interaction between rare disease-causing variants and common genetic variants for hereditary blood disorders.
Demographic Categories of Interest
This study will not center on underrepresented populations.
Data Set Used
Controlled TierDuplicate of Genetic resilience to hematological malignancies
Scientific Questions Being Studied
Somatic mosaicism is a widespread phenomenon that occurs increasingly with age in all human tissues. Clonal hematopoiesis (CH) is a prevalent form of somatic mosaicism in human blood. While blood cancer is highly heritable, and CH is widespread and a risk factor for developing blood cancers, the varying susceptibility of individuals with CH to develop blood cancer suggests the existence of genetic resilience variants that modulate the impact of acquired somatic mosaicism to prevent progression to cancer. Uncovering resilience loci will fill a critical knowledge gap on the molecular mechanisms involved in preventing transformation to malignancy, even in the setting of premalignant clonal expansions - a critical open question in the field of cancer biology. Long term, this work may help empower therapeutic strategies for preventing transformation into blood cancer.
Project Purpose(s)
- Disease Focused Research (Hematological malignancies)
- Ancestry
Scientific Approaches
Taking advantage of data from human population cohorts where blood cancers have been measured (primarily All of Us and UK Biobank cohorts), I will conduct well-powered genetic studies to elucidate the effects of germline and somatic resilience variants that can protect from the progression of clonal hematopoiesis (CH) into blood cancers. To uncover germline resilience variants, I will perform genetic association studies and statistical modeling focused on individuals with CH. Somatic resilience variants can be identified through the comparison of individuals with CH who remain healthy or progress to acquire a blood cancer. Upon identifying germline and somatic resilience variants, I will apply single-cell integrative functional genomics, genome editing, and cellular barcoding approaches to define the molecular mechanisms underlying resilience in the setting of hematopoietic clonal mosaicism.
Anticipated Findings
This work will address an important open question regarding the differences in the propensity for somatic mosaicism to evolve into cancer. Long term, this work may help empower therapeutic strategies for preventing transformation into blood cancer.
Demographic Categories of Interest
This study will not center on underrepresented populations.
Data Set Used
Controlled TierRequest a Review of this Research Project
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