Acute myeloid leukemia, or AML
Jianjun Chen, Ph.D.
, is one of the most common and fatal forms of blood-related cancers. Despite increased knowledge about who is at risk for AML and improved treatment-adapted strategies to fight the disease, over 70 percent of AML patients do not survive more than five years postdiagnosis. Which is why Jianjun Chen, Ph.D.
, a new faculty member at City of Hope, dedicates much of his research program to learning more about the disease.
Chen, the Simms/Mann Family Foundation Chair in Systems Biology, joined Beckman Research Institute
of City of Hope as a full professor and vice chair of the Department of Systems Biology in October 2017. He is a scholar of The Leukemia & Lymphoma Society and was named “Researcher of the Year” by the Pamela B. Katten Memorial Leukemia Research Foundation in 2014. Chen is also a permanent member of the National Institutes of Health Developmental Therapeutics study section and his research program is currently supported by four R01 grants from the National Cancer Institute.
“My research focuses on understanding the genetic — and especially epigenetic — changes, as well as the underlying molecular mechanisms in hematopoietic malignancies like AML, and on developing effective novel therapeutic strategies based on such understanding to treat leukemia,” said Chen, who notes his move to Beckman was influenced by long-term friendships and collaborations with current City of Hope investigators such as Markus Müschen
, M.D., Ph.D., founding chair of the Department of Systems Biology and The Norman and Sadie Lee Foundation Endowed Professor in Pediatrics, and Guido Marcucci
, M.D., chair of the Department of Hematologic Malignancies Translational Science
and director of the Gehr Family Center for Leukemia Research.
“With an emphasis on both clinical and translational research in hematopoietic malignancies, City of Hope is a perfect place for me to eventually translate the discoveries from our basic and translational research into patient treatments,” Chen said.
More specifically, Chen’s lab — which he launched at the Department of Medicine at University of Chicago in 2009 and then moved to the Department of Cancer Biology at the University of Cincinnati College of Medicine prior to coming to City of Hope — aims to better understand the molecular mechanisms underlying the development and drug resistance of AML. To that end, Chen and his colleagues have identified a set of genetic and epigenetic changes that play essential roles in the initiation, progression, maintenance and/or drug resistance of AML.
Reducing the side effects of therapies for AML is also of particular interest to Chen, as current treatment for AML frequently involves intensive, postremission regimens with multiple cycles of high-dose chemotherapy that impairs quality of life for patients. As a type of cancer that becomes more common as people age, the incidence of AML is continually rising and most older patients cannot bear intensive chemotherapy, which results in very poor survival rates. Thus, there is an unmet need to develop therapeutics with high efficacy and less toxicity, said Chen.
By better understanding the molecular mechanisms at play, Chen hopes to develop novel and targeted treatment strategies for AML with both improved effectiveness and minimal side effects. He and colleagues have developed several small-molecule compound inhibitors and microRNA-carrying nanoparticles to selectively target cancer-related RNA/DNA epigenetic modifiers or other cancer-causing genes. These inhibitors and microRNA-carrying nanoparticles have shown promising anti-AML effects in preclinical animal model studies and therefore hold therapeutic potential.
The long-term goal of my lab is to further advance our understanding of cancer biology, and AML in particular, and to translate our discoveries from basic research into clinical application,” said Chen, whose science has not been slowed by his transition to City of Hope.
In the past two months alone, he and colleagues have been especially prolific, publishing four papers in major journals that outline advances in their work.
The studies — “Targeted inhibition of STAT/TET1 axis as a therapeutic strategy for acute myeloid leukemia,” published in the Dec. 13, 2017, issue of the journal Nature Communications, “R-2HG exhibits anti-tumor activity by targeting FTO/m6A/MYC/CEBPA signaling,” published online Dec. 14, 2017 in Cell, "METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA m6A Modification" published online Dec. 28, 2017, in Cell Stem Cell, and “Recognition of RNA N 6-methyadenosine by IGF2BP proteins Enhances mRNA Stability and Translation,” published on Feb. 23 in Nature Cell Biology — all point to ways in which AML and other cancers may be targeted in new ways.
“My lab has made important progress in translational research in leukemia as evidenced by establishment of novel prognostic systems for outcome prediction and risk stratification and development of novel targeted therapy strategies and tools,” said Chen.
Based on the outcomes of recent these studies, Chen’s lab has filed four provisional patents and is currently working on further preclinical animal model studies, with the translational research goal of launching clinical trials to improve cancer therapy in the near future.
“Indeed, the cancer-associated genetic and epigenetic changes identified by us could serve as biomarkers for early diagnosis, as targets for new drug design and cancer therapy, and as indicators for treatment responsiveness and prognosis, which may ultimately lead to improved patient care and wellness,” said Chen.