# Nuclear body assembly and function in telomerase-free cancer cells

> **NIH NIH K22** · CARNEGIE-MELLON UNIVERSITY · 2020 · $166,088

## Abstract

My overall career goal is to become an established cancer cell biologist who employs multidisciplinary
approaches to determine how phase transition is used to promote cancer cell growth and to develop
strategies targeting these processes for cancer therapy. My interest in self-assembly of biological matter
originated from my Ph.D. work on molecular dynamics in lipid bilayers and postdoctoral work on phase
separation of RNA granules. Supported by the Physical Science Oncology Center (PSOC) at Penn, I started
working in cancer in my current postdoctoral position at Penn since 2015 and became interested in cell and
molecular physics of cancer. I decided to focus my independent research in this area and initiated a project
that I will bring with me to my future laboratory. My project concerns telomerase-negative cancer cells that rely
on an alternative lengthening of telomeres (ALT) pathway to maintain telomere length. The presence of ALT-
associated promyelocytic leukemia nuclear bodies (APBs) is a unique characteristic of ALT and is used for
diagnosis. APBs are essential for telomere maintenance in ALT, but both how they form and how they function
in telomere lengthening, which is a crucial part of the ALT cancer phenotype, are unknown. I observed that
APBs induced by DNA damage at telomeres exhibit behavior characteristic of liquid phase condensation,
leading me to hypothesize that telomere shortening in ALT cells induces nucleation of APB
condensates as a mechanism for telomere elongation. The liquid nature of APBs would promote
coalescence of APBs to cluster telomeres within APBs, another characteristic of ALT cells. Meanwhile,
condensation of APB droplets can concentrate DNA repair factors, providing opportunities for telomeres to use
one another as repair templates to elongate within APBs. I developed an optogenetic approach and induced de
novo assembly of APBs that exhibit liquid behavior and coalesce to drive telomere clustering. In this K22, I will
test my hypothesis for APB function to provide a basis for cancer therapy targeting APBs. Aim 1 focuses on the
dependence of APB function on their material properties by asking how APB formation drives telomere
clustering, and Aim 2 focuses on the dependence of APB function on their chemical composition by testing
whether APB formation is sufficient for telomere synthesis. I am negotiating my offers for the position of
Assistant Professor and plan to start my independent career earlier next year. With my multidisciplinary training
background and exciting preliminary data that supports my hypothesis, I am well positioned to achieve my
career objectives as an independent cancer researcher. However, to make the transition into cancer research
smooth and successful, further training to gain knowledge and technical expertise in cancer biology,
particularly on DNA repair and telomere biology, is much needed. Therefore, additional protected time from this
K22 is crucial for me to focus on research, imme...

## Key facts

- **NIH application ID:** 9910375
- **Project number:** 5K22CA237632-02
- **Recipient organization:** CARNEGIE-MELLON UNIVERSITY
- **Principal Investigator:** Huaiying Zhang
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $166,088
- **Award type:** 5
- **Project period:** 2019-04-08 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9910375

## Citation

> US National Institutes of Health, RePORTER application 9910375, Nuclear body assembly and function in telomerase-free cancer cells (5K22CA237632-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9910375. Licensed CC0.

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