1). Modulation of clonal hematopoietic development by inflammation
2). Non-genetic modifiers of somatic mutation effects in cancer
3). Cell fate decisions of hematopoietic stem cells
4). Single-cell multi-omics technology development
Cancer represents an evolutionary process through which growing malignant populations genetically diversify, leading to tumor progression and resistance to therapy. In addition to genetic diversity, the cell-to-cell variation that fuels evolutionary selection also manifests in cellular states, epigenetic profiles, spatial distributions and microenvironmental interactions. Therefore, the study of cancer requires the integration of multiple heritable dimensions at the resolution of the single cell - the atomic unit of somatic evolution. Thus, the Nam lab focuses on the development and application of single-cell multi-omics methods that enable the integration of multiple data modalities to inform the study of cancer. A centerpiece of these efforts was the development of Genotyping of Transcriptomes, by which we can determine the somatic mutation status together with whole transcriptomic data within the same thousands of single cells. By applying this technology to neoplastic blood development, we demonstrated that somatic mutations skew differentiation trajectories of hematopoietic stem cells. We also discovered that the downstream effects of somatic mutations are variable as a function of the underlying cell identity, revealing cell identity as a critical non-genetic modifier of somatic mutation effects.
Figure 1.
Representative heritable dimensions of a cancer cells that can be captured via single-cell multi-omics
Figure 2.
a. Workflows of combining single cell genotyping and whole transcriptomes. b. Wildtype (left) versus mutated (right) stem cells differentiate along distinct differentiation topographies. c. Somatic mutations impart distinct downstream effects in different cell states or identities.
Biography
Anna Nam received her bachelor’s degree at Davidson College and MD at University of Missouri. During medical school, she participated in the Howard Hughes Medical Institute-NIH Research Scholars (‘Cloisters’) Program. She completed her residency training in Anatomic Pathology and fellowships in Hematopathology and Molecular Genetics Pathology at WCM. For her post-doctoral training, she conducted single-cell genomics research with Dr. Dan Landau at WCM and the New York Genome Center. She was appointed Assistant Professor of Pathology and Laboratory Medicine in 2020, to start her research laboratory and serve on the molecular hematopathology service.
Distinctions:
American Society for Clinical Investigation Young Physician-Scientist Award (2021)
Burroughs Wellcome Fund Career Awards for Medical Scientists (2020)
NIH Director's Early Independence Award (2020)
K08 Clinical Investigator Award, NHLBI (2020)
Alpha Omega Αlpha (2013)
Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program (2011)
