Research on Metabolism and Cytokine Signaling Provides Clues to Disease Development

Learn how Jianhua Xiong, Ph.D., of Johns Hopkins All Children’s Institute for Fundamental Biomedical Research unravels some of the secrets of cell biology.

Jianhua Xiong, Ph.D.

Jianhua Xiong, Ph.D.

Published in Johns Hopkins All Children's Hospital - Fall 2021

Few of us spend much time thinking about fatty acid oxidation (FAO), metabolism, and cytokine signaling. Fortunately, Jianhua Xiong, Ph.D., does. His decade of research has been so important that he was recently recruited as a scientist and member of Johns Hopkins All Children’s Institute for Fundamental Biomedical Research and is now an assistant professor in the Division of Endocrinology, Diabetes and Metabolism at the Johns Hopkins University School of Medicine.

The Path to St. Petersburg

“I found cell biology amazing, and I was fascinated by the work that living cells do,” Xiong says with the same enthusiasm he had when he started his undergraduate studies. He has since devoted his career to unraveling some of the secrets of cell biology and, specifically, cellular metabolism, the integrated program of all chemical reactions within the body's cells that change food into energy for harmonic life.

Proud to have been the first in his family to go to university, Xiong graduated summa cum laude with a Bachelor of Science degree in biotechnology in 2007.

Beginning a Ph.D. program in 2007, Xiong investigated genetic regulators of estrogen receptors and their role in breast cancer, worked with high-throughput screening to identify small molecules and studied the role of microRNA in “cell signaling.” He received his Ph.D. in biotechnology in 2012 from the prestigious Peking University, the #1 university in China.

After receiving his Ph.D., he came to the United States for postdoctoral studies at the University of California, San Diego (UCSD) in the Division of Biological Sciences. While there, from 2012 to 2014, he investigated the mechanism of genetic stability in stem cells, among other questions.

Upon leaving UCSD, Xiong traveled to the National Institutes of Health’s National Heart, Lung, and Blood Institute (NHLBI), located just outside of Washington, D.C. At NHLBI he investigated mechanisms related to “cell fate” and aspects of the vascular and immune systems and their regulation. His work is fundamentally important to health and will eventually help us gain better understanding about the causes of some serious diseases and potentially open doors to cures.

He began his postdoctoral position at NHLBI working in the Center for Molecular Medicine (2014-2017). Next, he worked in the NHLBI Immunology Center (2017-2021) where he aggressively pursued the mechanisms behind alternative fates in living cells of the immune system. There, he focused much of his research on deciphering the connection between fatty acid oxidation (FAO), a key energy generating process, and cytokine signaling in immune cells which requires a major input of energy to allow the immune cells to ward off infection and limit disease development. Those fundamental processes are relevant to a broad range of diseases, including many inherited immunodeficiencies, cardiovascular disease and cancers, as well as autoimmune and allergic diseases.

Much of his work at NHLBI has led to a better understanding of how FAO regulates important biological processes in endothelial cells — cells that form a thin membrane that lines the inside of the heart and blood vessels throughout the body. These cells release substances that control blood vessel relaxation and contraction and the enzymes that control blood clotting, immune function and platelet action. Xiong spent time investigating a process by which FAO regulates a cell process called endothelial-to-mensenchymal transition (EndoMT). EndoMT, he explains, may contribute to a wide range of diseases affecting the heart, lungs and other organs when the process fails due to insufficient energy available because of a reduction in FAO. One therapeutic “counter move” might be to increase FAO during times when EndoMT is reduced because of a decrease in FAO. This hypothesis is based on Xiong’s research that was published in 2018 in the journal Molecular Cell.

During his time at NHLBI, Xiong also had additional training in Translational Research in Clinical Oncology at the National Cancer Institute (NCI) and in 2019 received training in bioinformatics and specifically next-generation sequencing data analysis.

When asked about his mentors, he smiles and says, “There have been so many, especially at NIH,” and cites two at NHLBI who were instrumental in their support — Warren Leonard, M.D., director of the NHLBI Immunology Center, and Toren Finkel, M.D., Ph.D., director of the NHLBI Center for Molecular Medicine.

Xiong is also developing into a mentor himself as while at NHLBI, he devoted time to “give back” by mentoring undergraduate students from Northern Virginia Community College.

A Passion for Metabolism and Cytokine Signaling

Xiong explains the yin and yang of metabolism — catabolism and anabolism. “Catabolism involves the breakdown of molecules and the release of energy, whereas, anabolism is the opposite because it consumes energy required to propel the metabolic reactions forward that build more complex molecules out of simpler building blocks.”

What fascinates him most, he says, is that the yin and yang of metabolism is kept in balance by a complex network of signaling pathways that are “re-wired” by the body and can quickly adapt to fit the metabolic needs of cells, and sometimes these adaptations can fail leading to disease.

“Finding ways to target the metabolic dependencies of abnormal cells may lead to promising therapies,” he suggests.

Xiong also continues to pursue a better understanding of “cytokine signaling.” He says that cytokines — small protein-chemical messengers — are crucial in controlling the growth and activity of immune system cells and other cells throughout the body. When released, cytokines instruct the immune system to do its job. Much of his work has focused specifically on cytokine signaling in T cells, one of the two major types of cells in the immune system that are triggered by cytokines to help protect the body from infection.

Building a Laboratory Team

Since his arrival at Johns Hopkins All Children’s, Xiong has been busy building his laboratory staff. He is in the process of recruiting two postdoctoral researchers to work at basic, molecular mechanistic levels to better understand the intersection between cell metabolism and cell “fate.” They will also be continuing to track down FAO’s role in changing the nature and structure of human cells, changes that can potentially cause serious disease and immune system disruption.

One of the new postdoctoral researchers will focus on the metabolic regulation of T cell differentiation and function, while the other will focus on endothelial cell function, metabolism and “cross-talk” with the immune system.

Much of this work will be basic “bench science,” but the research team will also work toward translating their findings from basic research to better understanding the causes and potential cures for myriad human diseases that affect both adults and kids – work that can eventually be incorporated into clinical practice. To do this, the lab partners he brings on board will, he says, be well-versed in systems cell biology to identify molecular and cellular targets that can be harnessed to develop new “immunotherapies,” or ways to enhance the immune system, and drug discovery.

“I am very excited about being here,” Xiong says.

“We are very excited to have recruited Dr. Jianhua Xiong to complement our developing program in the Institute for Fundamental Biomedical Research,” says Timothy Osborne, Ph.D., professor of Medicine and the associate dean for Basic Research at Johns Hopkins All Children’s Hospital. “He brings with him a unique expertise and perspective in the intersection between cellular metabolism and the immune system function, which is a very exciting area of current research.”