# Determining the role of LSD1 in multiple myeloma through a multi-omics approach at single cell resolution

> **NIH NIH F31** · HARVARD UNIVERSITY · 2024 · $32,372

## Abstract

PROJECT SUMMARY / ABSTRACT
Multiple myeloma (MM) kills nearly 13,000 people annually in the United States1. MM is preceded by a less life-
threating blood condition, which is similar to MM, yet non-lethal and asymptomatic2. in fact, most people don’t
even know they have it. An outstanding question in MM research is why some patients diagnosed with the
precursor condition go on to develop the full disease and why others do not. This question has been approached
from a genetics standpoint, however there is no clear genetic link defining who goes on to develop MM from a
precursor condition and who does not. Bone marrow creates a microenvironment to support developing blood
cells. Multiple myeloma hijacks the bone marrow microenvironment (BMM) to favor its own growth3. Without a
genetic driver of cancer development, I hypothesize that the BMM is modified epigenetically to facilitate the
selective growth of MM.
Epigenetics encompasses that which influences the expression of genes without altering the genes themselves.
Chromatin regulators (CRs) are proteins that mediate epigenetic changes through altering the ability of a cell to
express a given gene. CRs carry out this process through modifying the histone proteins around which genes
are wrapped (histones and DNA taken together comprise chromatin, hence: chromatin regulators). In addition to
these very specific functions, CRs can also mediate interactions with transcription factors (TFs), the proteins that
turn the expression levels of genes up or down. A specific CR LSD1, which is known to repress or turn off genes,
has been the target of other blood cancer diseases and drugs designed to block LSD1 activity are quite effective
in models of acute myeloid leukemia (AML)45. These drugs work by disrupting an interaction between LSD1 and
another protein. When that interaction is disrupted, a master TF is able to turn on genes that cause AML cells to
die5. Despite some similarities between AML and MM, treatment with LSD1-targeting drugs actually enhances
the growth of MM6. Interestingly, a small subset of patients have been found to be predisposed to MM
development through a heritable set of mutations in LSD1 – these mutations mimic mutations that confer drug
resistance in AML5,6. While these mutations only make up a small fraction of MM cases, it points to LSD1 as a
key component in the development of MM7. I thereby hypothesize that LSD1 plays a role in the progression of
MM; this role is potentially specific to the BMM. The specific aims of this project can be summarized as follows:
 1. Develop a computational tool using novel techniques from machine learning and mathematics to learn
 about factors that drive the BMM to contribute to the progression of MM.
 2. Collect BMM samples from patients across a spectrum of MM development to analyze single cell gene
 expression and chromatin accessibility data to learn the ways in which the epigenome is altered as MM
 progresses in the BMM.

## Key facts

- **NIH application ID:** 10747335
- **Project number:** 5F31CA257625-04
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Michael Edward Vinyard
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $32,372
- **Award type:** 5
- **Project period:** 2021-01-04 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10747335

## Citation

> US National Institutes of Health, RePORTER application 10747335, Determining the role of LSD1 in multiple myeloma through a multi-omics approach at single cell resolution (5F31CA257625-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10747335. Licensed CC0.

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