# Myc promoted changes to the glycocalyx in leukemia

> **NIH NIH F30** · STANFORD UNIVERSITY · 2020 · $50,461

## Abstract

PROJECT SUMMARY
The transcription factor c-MYC (MYC) is overexpressed in a majority of human malignancies and is associated
with aggressive cancer phenotypes and poor patient outcomes. Recently, MYC was implicated in promoting
leukemia's evasion of the immune system by up-regulating checkpoint proteins that suppress immune cell
function. However, our understanding of how MYC shapes the tumor microenvironment is incomplete.
Glycosylation of cancer cells could be part of the answer. Specifically, tumor cell oligosaccharides containing
sialic acid (sialosides) are known to engage Siglec receptors on white blood cells such as natural killer cells
and macrophages. The Siglecs are a family of receptors that, like the checkpoint proteins PD-1 and CD47,
contain signaling domains capable of preventing immune activation. Therefore, display of sialosides is a
strategy employed by tumors to evade the immune system. As a transcription factor and regulator of cellular
metabolism, MYC is a likely culprit behind cancer's presentation of sialosides that regulate the immune
system. I found that MYC directly regulates the sialyltransferases, the enzymes that append sialic acid to
oligosaccharides. This proposal builds off these findings with the goal of characterizing sialosides capable of
inhibiting the immune system in models of MYC driven leukemia. Using genetic and chemical tools, I will
delineate the mechanism of sialoside synthesis promoted by MYC in cancer (Aim 1). I will then study these
sialosides using in vivo models of leukemia to determine how MYC's modulation of glycosylation affects
macrophage function in particular, and the tumor microenvironment in general (Aim 2). A mechanistic
understanding of sialoside synthesis in MYC driven leukemias, and the downstream modulation of immune
function, will promote the development of novel immunotherapies targeting sialic acid and glycosylation.
The project presented herein will provide me with ample opportunities to develop academic and professional
skills as I continue my training to become a clinician investigator. The work I present will take place at Stanford
University in the lab of Carolyn Bertozzi, a prominent chemist and glycobiologist, who will mentor me as I
become an independent investigator. I will be further advised by oncologists and tumor immunologists Dean
Felsher, MD PhD; and Ravi Majeti, MD PhD. The resources and environment at Stanford are ideal for
supporting me toward becoming a hematologist-oncologist with my own laboratory.

## Key facts

- **NIH application ID:** 9950841
- **Project number:** 5F30CA232541-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Benjamin Arthur Humphers Smith
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,461
- **Award type:** 5
- **Project period:** 2019-09-16 → 2021-12-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9950841

## Citation

> US National Institutes of Health, RePORTER application 9950841, Myc promoted changes to the glycocalyx in leukemia (5F30CA232541-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9950841. Licensed CC0.

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