Hematopoietic stem cells (HSCs) maintain the adult blood and immune systems throughout the lifetime
of an organism. While HSC transplants are used clinically for the curative treatment of patients with leukemias,
lymphomas, and immune disorders, the success of HSC transplants varies considerably, with some patients
having to undergo multiple transplants due to inefficient HSC engraftment. The goal of the proposed project is
to identify how the heparan sulfate proteoglycan, Syndecan-2, regulates HSC maintenance and regeneration.
Aim 1 will utilize newly generated tissue-specific knockout mice to analyze the contribution of Syndecan-2 in
regulating HSC engraftment, while performing a structure-function analysis of the molecular motifs of Syndecan-
2 in mediating engraftment and niche regeneration. Aim 2 will analyze the role of Syndecan-2 in regulating
hematopoietic recovery from stress by combining radiation injury and myelosuppression in vivo models of HSC
self-renewal. These experiments will demonstrate the role of Syndecan-2 in mediating HSCs maintenance and
regeneration, providing foundational knowledge to enable further study of how proteoglycans regulate HSCs.
The knowledge procured from the completion of the proposed aims is expect to have broad potential
contributions to patients undergoing chemotherapy and radiation therapy as a part of their treatment regimen for
variety of cancers, immune diseases, leukemias and anemias and therapeutic value from a public health
standpoint for treating patients that experience accidental radiation exposure.
My career goals are to become an assistant professor at a top-tier academic research institution. I aim
to lead a research program that investigates how proteoglycans regulate HSCs and the HSC microenvironment
at homeostasis and during stress. To achieve these goals, the proposed project has embedded training in
modeling HSC recovery from injury, while expanding my knowledge of glycobiology and growth factor signaling.
Under this award, I will pursue the proposed training with the mentorship of Dr. John Chute (UCLA), who has
substantial experience in translational modeling of HSC and niche regeneration, while supported by an Advisory
Committee with expertise in stem cell biology, growth factor signaling and proteoglycan biology. As a
postdoctoral fellow, I will present my work at international conferences and to my mentoring committee, which
consists of experts in the field. As junior faculty, I will receive training in laboratory management/leadership, grant
writing, negotiation, and mentoring to help me lead a successful research team. The proposed project will allow
me to transition to an independent research position while developing my skillset in HSC biology. UCLA has
superb research facilities, professional development resources and administrative support, which will provide
the necessary infrastructure to support my research and career development as a mentored postdoctoral fellow
and ultimately, my transition to independence.