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City of Hope Research Spotlight, April/May 2025

New insights into midlife weight gain, a potential therapeutic target for acute myeloid leukemia and the cumulative impact of subtle workplace discrimination

2025-07-08
(Press-News.org) LOS ANGELES — City of Hope® Research Spotlight offers a glimpse at groundbreaking scientific and clinical discoveries advancing lifesaving cures for patients with cancer, diabetes and other chronic, life-threatening diseases. Each spotlight features research-related news, such as recognitions, collaborations and the latest research defining the future of medical treatment.

To learn more about research at City of Hope, one of the largest and most advanced cancer research and treatment organizations in the United States with its National Medical Center named a Top 5 “Best Hospital” in the nation for cancer care by U.S. News & World Report, subscribe to City of Hope Research Spotlight.

Study Helps Explain Why Belly Fat Increases in Middle Age

As people reach middle age, they often gain more body fat, especially in the belly. This fat, which accumulates around the organs, is linked to age-related metabolic disorders, including diabetes.

City of Hope researchers investigated this process at the cellular level. Their aim: to understand how the process of adipogenesis, or the formation of fat cells, changes with age.

Led by City of Hope staff scientist Guan Wang, Ph.D., and Qiong (Annabel) Wang, Ph.D., associate professor in the Department of Molecular & Cellular Endocrinology at City of Hope, the team conducted a mouse study to investigate the role of adipose progenitor cells (APCs), a type of cell that may develop into fat.

They found that APCs were mostly dormant in young mice. However, they became much more active in middle age, leading to the rapid proliferation of new fat cells. This was the main driver leading to an increase in belly fat, especially in male mice. The team identified a new type of cell, called committed preadipocyte, age-enriched (CP-A), which increases in middle age and is especially good at creating fat cells. Researchers also found that a protein called LIFR plays an important role in turning CP-A into fat.

These insights could be an important clue to preventing or treating midlife weight gain and age-related metabolic disorders. For more information, see the paper in Science.

Researchers Validate a New Therapeutic Target for Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is an aggressive, often deadly form of blood cancer. It occurs when immature white blood cells, called myeloid blasts, begin to multiply uncontrollably.

New research led by Flavia Pichiorri, Ph.D., M.S., a professor in the Department of Hematologic Malignancies Translational Science at City of Hope, has further validated CD84 as a potential target for AML. The team conducted cell and mouse studies to investigate the role of CD84, which is overexpressed in AML cells. They found that CD84 plays an important role in helping leukemia cells survive.

Researchers observed that leukemia cells with high levels of CD84 were more likely to survive and grow, while blocking CD84 slowed down the cancer. When scientists looked closer at how CD84 was helping AML cells, they found that it regulated the cells’ energy and metabolism. It also helped protect the cells’ mitochondria, tiny structures that help cells turn nutrients into energy, from oxidative stress.

The findings build upon the earlier identification of CD84 as overexpressed in AML and suggest that CD84 could be a potential vulnerable target to fight the disease.

For more information, see the study in the Journal of Clinical Investigation, with co-first authors Yinghui Zhu, Ph.D., and Mariam Murtadha, Ph.D., Beckman Research Institute of City of Hope staff scientist.

* City of Hope licensed certain CD84 targeting technology to Slam Bio. Dr. Pichiorri is co-inventor of that technology; she and City of Hope may receive royalties from the company. Dr. Pichiorri is a paid consultant to the company.

Subtle Challenges to Women’s Authority Increases Burnout

It’s widely thought that women face discrimination in the workplace, but only 18% of women report personally experiencing gender discrimination.

Now a new City of Hope investigator-led study shows how subtle challenges to women’s authority accumulate over time, leading to increased rates of burnout, discouraging women from staying in male-dominated careers. Importantly, the study showed how these repeated challenges may have a negative effect on women even when they don’t perceive it as discrimination.

The team, led by Amy Y. Chen, M.D., M.P.H., M.B.A., F.A.C.S., chief of surgery and director of thyroid oncology at City of Hope Cancer Center Atlanta, recorded the workplace experiences of female and male surgeons at four U.S. surgical residency programs over five months.

Researchers found that female surgeons were more likely than men to have their role challenged or their authority questioned. One surgeon said she was mistaken for janitorial staff; another said a scrub tech refused to pass her instruments during surgery. Regardless of gender, surgeons who experienced more frequent or intense challenges to their authority were more likely to report burnout and less likely to plan to continue in their career.

The findings offer new insight into how even hard-to-detect discrimination can increase burnout and turnover among health care professionals, and how women may be impacted by sexism even when they aren't sure it's happening. To learn more, read the article in PNAS.

Awards and Honors

Miguel Zugman, M.D., City of Hope postdoctoral medical oncology research fellow, received a 2025 Conquer Cancer endowed merit award from the ASCO Foundation that was presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

City of Hope former chief fellow Alexis LeVee, M.D., was a recipient of the 2025 Conquer Cancer Young Investigator Award, which is awarded by the ASCO Foundation to promising young physicians during their final years of training.

Research Funding

Virginia Sun, Ph.D., M.S.N., R.N., and Saro Armenian, D.O., M.P.H., received a $5.3 million grant from the Department of Defense’s Congressionally Directed Medical Research Programs for a project entitled “Digital Health Intervention for Self-Management and Telemonitoring in Chimeric Antigen Receptor-T Cell Therapy.”

Jeffrey Y.C. Wong, M.D., Flavia Pichiorri, Ph.D., M.S., and John Shively, Ph.D., received a $3.7 million grant from the National Institutes of Health/National Cancer Institute for a project entitled “Anti-CD38 Radioimmunotherapy and Total Marrow Irradiation for Treatment of Relapsed and Refractory Acute Myelogenous Leukemia.”

Saswati Chatterjee, Ph.D., and Vinodh Narayanan, M.D., clinical professor at Translational Genomics Research Institute (TGen), part of City of Hope, received a $3.6 million grant from the National Institutes of Health/National Institute of Neurological Disorders and Stroke for a project entitled “High Fidelity Genome Editing for the Correction of MECP2 Mutations and Physiologic Regulation of Expression in Rett Syndrome.”

Hua Yu, Ph.D., received a $2.9 million grant from the National Institutes of Health/National Cancer Institute for a project entitled “The Role of IL-6/STAT3 Signaling in CIC-DUX4 Fusion Sarcoma Metastasis and Immunosuppression.”

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About City of Hope

City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest and most advanced cancer research and treatment organizations in the United States, and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center that is ranked a Top 5 “Best Hospital” in the nation for cancer care by U.S. News & World Report at its core, City of Hope’s uniquely integrated model spans cancer care, research and development, academics and training, and a broad philanthropy program that powers its work. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM. For more information about City of Hope, follow us on Facebook, X, YouTube, Instagram and LinkedIn.

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[Press-News.org] City of Hope Research Spotlight, April/May 2025
New insights into midlife weight gain, a potential therapeutic target for acute myeloid leukemia and the cumulative impact of subtle workplace discrimination