Since 2014, the American Association for Cancer Research (AACR) has provided the opportunity for graduate students, postdocs, and assistant professors to give high-profile presentations at the AACR Annual Meeting as part of its NextGen Stars Program. This year, 11 early-career researchers were selected based on their outstanding applications.

Learn more about one of the newest NextGen Stars below, and check out the Q&As with other members of the NextGen Stars Class of 2025.

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Stephanie Xie, PhD
AACR NextGen Stars Class of 2025
Affiliate Scientist
University Health Network Princess Margaret Cancer Centre, Toronto, Ontario

Abstract Presentation:
Inflammatory memory and selective advantage in human clonal hematopoiesis

Session Details:
SY02 – Clonal Hematopoiesis and Beyond: The Aging Immune System in Cancer
Monday, April 28, 10:15-11:45 a.m. CT
Room S404, McCormick Place South (Level 4)

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What is the subject of your research?

My research focuses on the functional characterization of stemness programs in human hematopoietic stem cells (HSCs) and how they are perturbed in hematological malignancies. I have a particular interest in understanding how metabolic and inflammatory stress response programs in human HSCs are directly linked to risk for diseases associated with aging and inflammation, e.g., cancer.

We recently found that inflammatory stress in a human hematopoiesis xenograft model replicates many of the transcriptional and epigenetic changes enacted during aging, but only in a subset of cells termed HSC inflammatory memory (HSC-iM). HSC-iM accumulates during aging and in individuals with clonal hematopoiesis of indeterminate potential (CHIP), an aging-associated phenomenon in which HSCs acquire somatic mutations that result in clonal expansion of mutated blood cells. As many of the mature myeloid cells that respond to inflammation are extremely short-lived, HSC-iM may be the missing link to discovering how inflammation in some people drives cancer risk and progression as we age.

What sparked your interest in this area of research, and why is it important?

A fundamental challenge in cancer research is to understand why some people develop cancer and others age well. Understanding the molecular mechanisms that lead to that dichotomy could lead to meaningful methods for holding the risk for cancer in check and promoting healthy aging.

It makes sense to me to focus on our tissue stem cells, such as HSCs, as their entire job is to sustain tissue integrity for our lifetime. Blood is a remarkably proliferative tissue. We produce upwards of half a trillion new blood cells each day. Blood cells also infiltrate all other tissues in our body. But if something goes wrong in a single HSC clone, such as the acquisition of a somatic mutation that predisposes for cancer (such as CHIP), then all the progeny will inherit this mutation. For example, if this mutation promotes inflammation, it could have far-reaching systemic ramifications.

I have a long-standing interest in the molecular mechanisms underlying aging and longevity dating back to my PhD days. My thesis work, supervised by Peter Sorger, PhD, was focused on genome integrity mediated by the spindle assembly checkpoint. I was also inspired by the interactions with Leonard Guarente, PhD, and his research group and their pioneering work on the genetics of aging. I was particularly struck by how metabolism could directly impact physiology. I have benefited from outstanding and supportive mentorship from David Scadden, MD, and John Dick, PhD, FAACR, to pursue my interest in metabolic regulation of HSCs in mice and humans. Such inquiry has brought me to my current research program to understand how human HSCs respond and adapt to inflammatory stress and that metabolic intervention could be the key to mitigating the detrimental impacts of inflammation on HSCs.

What (or who) inspired you to apply for the NextGen Stars program?

The goals of the AACR—to prevent and cure cancer—resonate deeply with me. I believe the pathway to achieving those goals is through basic research. We are living in a world where our population continues to age. We passed a pivotal inflection point in 2020 when the number of people over age 60 eclipsed children that are 5 years of age or younger. We really must continue to support research on preventing cancer and supporting healthy aging. The NextGen Stars program is an opportunity to call attention to a basic research program focused exclusively on primary human tissue stem cell research with underlying goals of understanding cancer risk and prevention.

What do you hope to take away from your experience as a NextGen Star and your time at the AACR Annual Meeting 2025?

The opportunity to interact with the best and brightest in the world of cancer research is very exciting. I am looking forward to making new connections and gaining valuable knowledge that crosses research fields.