Dr. Wu’s research at the Neuro-Oncology Branch is primarily focused on the clinical aspects of gliomas, which are rarely fully curable—whether or not they’re diagnosed as low- or high-grade tumors. Gliomas also exhibit high levels of heterogeneity, making them challenging to treat long-term. Isocitrate dehydrogenase (IDH) genes are mutated in approximately five percent of all gliomas and eighty percent of low-grade gliomas, causing 2-hydroxyglutarate (2-HG) to accumulate and leading to increased tumorigenic potential. While individuals with IDH-mutant low-grade gliomas often have slower disease progression and respond more favorably to treatment than those with IDH wildtype tumors, almost all cases eventually transform into more aggressive high-grade gliomas that rapidly progress.
As there are significant gaps in knowledge regarding how and why this transformation to high-grade disease occurs, the first facet of Dr. Wu’s research focuses on developing a diagnostic tool to detect this transformation as early as possible in patients. This project utilizes the fact that levels of 2-HG and/or metabolic flux may change as high-grade transformation takes place. This is because glioma cells must undergo a metabolic shift to aerobic glycolysis, in order to support their rapid growth. The level of 2-HG can be detected using 1H based magnetic resonance spectroscopic imaging (MRSI), and the metabolic flux can be detected by administering a 13C hyperpolarized pyruvate MRSI noninvasively into the patient—resulting in real-time tracking of the tumor’s changes. These techniques will hopefully assist in uncovering the intracellular changes that indicate tumor progression without the need for biopsy or surgery.
Once gliomas transform to high-grade status, those with increased mutational burden may respond better to immunotherapy. One key feature of high-grade gliomas is the enormous intra- and inter-tumoral heterogeneity that drives their aggressiveness and therapy resistance. To combat this, Dr. Wu’s second project elucidates whether TG02, a multi-kinase inhibitor, primarily inhibits cyclin-dependent kinase 9 (CDK9) and can target multiple cancer survival pathways simultaneously. This agent can cross the blood-brain barrier, making it a favorable candidate for glioma treatment. It has also shown preclinical benefit when combined with Temozolomide, a common alkylating chemotherapeutic agent in brain tumor treatment. This research has led to an actively recruiting Phase I/II clinical trial for patients with recurrent high-grade gliomas.
Dr. Wu received her Doctor of Medicine degree from Capital Medical University in Beijing, China prior to moving to the United States and pursuing her Ph.D. in neuroscience from the University of Texas Medical Branch at Galveston. She subsequently completed an NIH postdoctoral fellowship under William D. Willis, who was a significant contributor to the fields of pain and neuroscience and a lifelong mentor to Dr. Wu. Following her Ph.D., she completed an internship in internal medicine at Texas Tech University Medical Center, followed by a neurology residency at The University of Texas Health Science Center (where she also served as the chief resident), and a Neuro-Oncology fellowship at The University of Texas MD Anderson Cancer Center. She then joined the University of North Carolina (UNC) at Chapel Hill as a tenure-track assistant professor in the Department of Neurosurgery and Neurology. She served as the co-director of the Brain Tumor Program at the Lineberger Comprehensive Cancer Center and developed a clinical and translational research program in neuro-oncology at UNC. Dr. Wu joined the Neuro-Oncology Branch (NOB) in 2015 as a staff physician, and soon became the director of the Neuro-Oncology Fellowship Program as well as a tenure-track investigator overseeing multiple clinical trials.
Dr. Wu is certified both by the American Board of Psychiatry and Neurology (ABPN) in neurology and the United Council for Neurologic Subspecialties (UCNS) in neuro-oncology. She has published over 50 peer-reviewed articles while also serving as an invited reviewer for several prestigious journals. She has received impressive awards over her training and clinical tenure, including the William James Miller Endowed Fellowship Award in Neuro-Oncology and the NIH/NCI Paul Calabresi Clinical Oncology Scholar Award. In 2018, she was awarded the NIH-Lasker Clinical Research Scholar Award—a prestigious opportunity that provides funding and support for exceptional clinical researchers to develop their clinical research programs.
Honors, Awards and Leadership
- NIH-Lasker Clinical Research Scholar - 2018
- NIH/NCI Paul Calabresi Clinical Oncology Scholar Award (K12 Career Award) - 2011-2014
- Junior Faculty Scholarship for “Translational and Clinical Research Course for Clinician-
- Scientist” (American Neurological Association) - 2011
- William J. Miller Endowed Fellowship Award in Neuro-Oncology (MD Anderson Cancer Center) - 2009
- Frank M. Yatsu MD Excellence in Residency Award (University of Texas Health Science Center) - 2008
- Teva Neuroscience Excellence in Teaching Award (University of Texas Health Science Center) - 2008
- Residents’ Scholarship Award (American Academy of Neurology) - 2006
- Jeanne B. Kempner Scholar Award (Jeanne B. Kempner Research Foundation) - 2000-2001
- Curtis W. Lambert Scholarship Award (University of Texas) - 1999
- George Sealy Excellence Research Award in Neurology (University of Texas) - 1998
- Anatomy and Neuroscience Research Award (39th National Student Research Forum) – 1998
Societies and Initiatives
- Center for Cancer Research (CCR) Science Board Member, NCI, NIH (2016 to present)
- Regular Study Section Member, Grant Reviewer, CSR, NIH (2019 to present)
- Clinical Oncology Study Section (CONC), CSR, NIH
- Society for Neuro-Oncology 2008 - present
- Society for Neuroscience (2000-2010)
- American Society of Clinical Oncology (ASCO) (2008-2015)
- Collaborative Ependymoma Research Network (CERN), 2011- present Brain Tumor Trials Collaboratives Consortium (BTTC), 2011- present
- Ranjan S, Quezado M, Garren N, Boris L, Siegel C, Lopes Abath Neto O, Theeler BJ, Park DM, Nduom E, Zaghloul KA, Gilbert MR, Wu J. Clinical decision making in the era of immunotherapy for high grade-glioma: report of four cases. BMC Cancer. 2018;18(1):239.
- Su YT, Chen R, Wang H, Song H, Zhang Q, Chen LY, Lappin H, Vasconcelos G, Lita A, Maric D, Li A, Celiku O, Zhang W, Meetze K, Estok T, Larion M, Abu-Asab M, Zhuang Z, Yang C, Gilbert MR, Wu J. Novel Targeting of Transcription and Metabolism in Glioblastoma. Clin Cancer Res. 2018;24(5):1124-1137.
- Wu J, Frady LN, Bash RE, Cohen SM, Schorzman AN, Su YT, Irvin DM, Zamboni WC, Wang X, Frye SV, Ewend MG, Sulman EP, Gilbert MR, Earp HS, Miller CR. MerTK as a therapeutic target in glioblastoma. Neuro Oncol. 2018;20(1):92-102.
- Lu Y, Kwintkiewicz J, Liu Y, Tech K, Frady LN, Su YT, Bautista W, Moon SI, MacDonald J, Ewend MG, Gilbert MR, Yang C, Wu J. Chemosensitivity of IDH1-Mutated Gliomas Due to an Impairment in PARP1-Mediated DNA Repair. Cancer Res. 2017;77(7):1709-1718.
- Wu J, Armstrong TS, Gilbert MR. Biology and management of ependymomas. Neuro Oncol. 2016;18(7):902-13.
Related Scientific Focus Areas
This page was last updated on Wednesday, December 7, 2022