# Defining the Biological and Mechanistic Implications of XPO1 Mutations in Hematologic Malignancies

> **NIH NIH K08** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2021 · $213,106

## Abstract

Candidate: Justin Taylor is an Instructor in Medicine at Memorial Sloan Kettering Cancer Center and
Attending on the Leukemia Service at Memorial Hospital. He has been working with his proposed K08 mentor,
Dr. Omar Abdel-Wahab, to learn about targeting splicing factor mutant leukemias in translational preclinical
models and now has begun independent work to discover the role of XPO1 hotspot mutations in hematologic
malignancies as a potential therapeutic target. His goal is to develop an independent research program over
the next 5 years and have an independent laboratory doing translational hematologic malignancies research.
Career Development Plan: Dr. Taylor has strategically planned to address the necessary training and
mentoring that will be required for his successful career transition to independence over the next few years
through select coursework and a robust mentoring plan. He has also organized an advisory committee
composed not only of leaders in the field but also those able to directly impact his career advancement. This
will not only ensure that Dr. Taylor's research project progresses as planned, but also that his progress is
recognized by promotion and support in garnering independent research funding. He has a very exciting
research project that is sufficiently different from his mentor's research to avoid competition or overlap.
Research Plan: Large discovery sequencing projects of cancer sub-types, such as The Cancer Genome
Atlas, have identified a multitude of novel recurrent mutations in protein coding genes. The ultimate goal of
these sequencing efforts is to lead to improved therapies for patients with cancer and will require
understanding how these mutations mechanistically contribute to carcinogenesis. However, even when the
function of a gene is known, the biological effect of the mutation cannot always be inferred from the coding
sequence. In this proposal, we plan to discover the biological relevance of somatic mutations in the nuclear
transport protein XPO1. Somatic mutations in XPO1 have been demonstrated in solid and hematologic
malignancies, including ~10% of cases of chronic lymphocytic leukemia and 25% of cases of primary
mediastinal B-cell lymphoma and classical Hodgkin lymphoma. Selective inhibition of nuclear export by
inhibiting XPO1 has been utilized as an antineoplastic agent in current Phase I/II clinical trials. Yet, despite
recognition of XPO1 as a potential driver of cancer, there has been no direct demonstration of the oncogenic
potential of somatic mutations in XPO1. We plan to explore the effects of these mutations by using isogenic
cell lines, genetically engineered mouse models and human tissues. Furthermore, since XPO1 is a nuclear
exporter, we will study the effect of these genetic alterations on protein subcellular localization. Lastly, we aim
to determine the effects of XPO1 mutations on response to XPO1 inhibitors currently in development. The end
goal of this research will be to discover th...

## Key facts

- **NIH application ID:** 10245306
- **Project number:** 5K08CA230319-04
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Justin Taylor
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $213,106
- **Award type:** 5
- **Project period:** 2018-08-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10245306

## Citation

> US National Institutes of Health, RePORTER application 10245306, Defining the Biological and Mechanistic Implications of XPO1 Mutations in Hematologic Malignancies (5K08CA230319-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10245306. Licensed CC0.

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