ABSTRACT
The ultimate goal of this proposal is to verify an RNA liquid biopsy platform and transition it to have specific utility
for the study, and non-invasive assessment, of the hematopoietic bone marrow (BM) niche. In addition to their
reliance of material excreted from dying, diseased cells, cell-free DNA (cfDNA) platforms are limited to primarily
detecting changes in somatic genomic sequence, copy number, or methylation status. Many biological and
clinical events, such as hematopoiesis, fibrosis, and tumorigenesis, are executed via global changes in
transcriptional regulation. My PhD advisor Dr. Daniel Kim and I have established a platform for exRNA liquid
biopsy in human blood-plasma that has demonstrated significant diagnostic and monitoring potential in both
Pancreatic cancer and COVID-19 patients. I propose to continue this research to complete my PhD by
assessing diagnostic performance of the exRNA platform in a new cohort of 60 lung adenocarcinoma
(LUAD) patients with matched controls. Furthermore, I will apply my expertise in exRNA liquid biopsies to
assay the transcriptional dynamics of hematopoiesis and hematopoietic stem cells (HSCs) in the bone marrow
(BM) niche. Currently, bone marrow biopsies or aspirations are used to determine bone marrow health and
production. These techniques are costly and require sedation and/or pain relief for the subject and have the
potential to lead to long term discomfort, infection, excessive bleeding, and other side-effects. BM aspirations
remain a critical diagnostic and monitoring tool for HSC transplant recovery, leukemias and lymphomas, blood
cell pathologies, and infections of unknown origin but the primary readout remains identification and counting of
cell types. I hypothesize that hematopoietic lineages within the BM secrete exRNA that reflect cell state and
identity that can be used in a non-invasive RNA liquid biopsy for detailed study of transcription and populations
within the BM. I propose to identify exRNA expressed and secreted by HSCs and the remaining
hematopoietic lineage in order to develop a platform to deconvolute peripheral blood into constituent
hematopoietic cell types without the need for HSC mobilization.