Zhengping Zhuang, M.D., Ph.D.
Building 37, Room 1000 Bethesda, MD 20892
The root of Dr. Zhuang’s research is based on the inherited and somatic mutations that result in cancer and understanding how they can contribute to the development and progression of tumors, and particularly brain tumors. The laboratory utilizes clinical, translational, and basic approaches to study the basic science as a foundation that gives way to understanding the pathological changes that are present in tumors. There are three on-going multidisciplinary projects: 1) investigation of hypoxia signaling and tumor development, 2) investigation into the impact of patient-derived IDH1 mutant mosaicism on brain tumor development, and 3) development of therapeutics for cancers of the central nervous system. Project 1 centers around investigation of gain-of-function of hypoxia inducible factor 2a (HIF2a), which was first found in a combined clinical and scientific effort culminating in the discovery of Pacak-Zhuang syndrome. In this project, his lab is investigating the unusual phenotypes recently identified in the patients with the syndrome and the mouse model, including sexual dimorphism and HIF2a gene genomic imprinting. The findings in these studies will substantially advance our understanding of HIF2a impact on biology and pathobiology, including this syndrome and hypoxia signaling in brain tumors. Project 2 began with a critical observation of two patients, identical twins, with low-grade gliomas. This observation provides important information that IDH1 mutation in early development has two possibilities: 1) it may remain quiescent or in the “pre-tumor state” throughout development or 2) it may acquire additional mutations which allow the cell to transform to a tumor. Since Dr. Zhuang discovered glutamine synthestase, which is important in IDH-mutant tumors and astrocytoma specifically, the lab is well-primed to deduce the basic physiology that can result in a brain tumor. The research group was able to deduce using deep PCR techniques that an inherent and embryonic IDH1 mutation triggered a tumor with p53. His lab also uses induced pluripotent stem (iPS) cells to determine how the IDH mutation can drive tumor growth by studying the 2-hydroxyglutarate (2-HG) and glutamate cycle. Project 3 has several arms. First, Dr. Zhuang’s lab continued to work on the development of an immunomodulator called LB100, which acts by inhibition of protein phosphatase 2A. This has entered clinical trials. Second, his lab have developed CAR-T cells aimed at hypoxia signaling downstream product, carbonic anhydrase IX. Third, they have developed a modulator of HIF2a, which has allowed to further explore the pathway.
Dr. Zhuang received his Doctor of Medicine (M.D.) degree from Shanghai Jiao Tong University School of Medicine (formerly Shanghai Second Medical University) in China and completed a short residency in General Surgery at Ruijin Hospital affiliated with the medical school before moving to the United States to pursue a Doctor of Philosophy (Ph.D.) degree in Pharmacology from Wayne State University in Detroit, Michigan. Following his doctorate, he was a postdoctoral fellow at Massachusetts General Hospital for a year and shortly thereafter relocated back to Michigan to be a resident in Translational Medicine at Henry Ford Hospital. He then served as a research associate at University of Michigan and moved to the NIH in 1993 as a resident in Anatomic Physiology at NCI’s Department of Pathology. He was named Special Expert and Staff Pathologist for the Surgical Neurology Branch, a position he served for 17 years. Dr. Zhuang joined the Neuro-Oncology Branch in 2017 as a Senior Investigator.
In addition to his extensive research experience and tenure in multiple branches at NIH, Dr. Zhuang is also licensed to practice medicine in the District of Columbia and holds a completion certificate for an Anatomic Pathology Residency. He also currently holds 5 patents, with 11 patents pending, highlighting the novelty of his research endeavors.
Honors, Awards and Leadership
- Isolation of cellular material under microscopic visualization using an adhesive/extraction reagent tipped probe, US Patent #5843644
- Isolation of cellular material under microscopic visualization, US Patent #6010888
- Isolation of cellular material under microscopic visualization, US Patent #6204030
- Isolation of cellular material under microscopic visualization, US Patent #6569639
- The gene associated with Multiple Endocrine Neoplasia type 1, menin polypeptides, and uses thereof, US Patent # 7358347
- The Federal Technology Transfer Award, 2019
- The Federal Technology Transfer Award, 2018
- Cy Katzen Humanitarian Award, 2014
- Federal Laboratory Consortium Award for Excellence in Technology Transfer, 2010
- NIH APAO Outstanding Achievement Award, 1999
- Gordon F. Vawter Award, Society for Pediatric Pathology, 1996
- NCI New Invention and Technology Development Award, 1995
- American Society of Clinical Pathologists Resident Award in Anatomic Pathology, 1994
- Stowell-Orbison Award for Pathologist-in-training, U.S. and Canadian Academy of Pathology, 1994
Gordon IK, Lu J, Graves CA, Huntoon K, Frerich JM, Hanson RH, Wang X, Hong CS, Ho W, Feldman MJ, Ikejiri B, Bisht K, Chen XS, Tandle A, Yang C, Arscott WT, Ye D, Heiss JD, Lonser RR, Camphausen K, Zhuang Z. Protein Phosphatase 2A Inhibition with LB100 Enhances Radiation-Induced Mitotic Catastrophe and Tumor Growth Delay in Glioblastoma. Mol Cancer Ther. 2015;14(7):1540-1547.
Yang C, Swallows CL, Zhang C, Lu J, Xiao H, Brady RO, Zhuang Z. Celastrol increases glucocerebrosidase activity in Gaucher disease by modulating molecular chaperones. Proc Natl Acad Sci U S A. 2014;111(1):249-54.
Pacak K, Jochmanova I, Prodanov T, Yang C, Merino MJ, Fojo T, Prchal JT, Tischler AS, Lechan RM, Zhuang Z. New syndrome of paraganglioma and somatostatinoma associated with polycythemia. J Clin Oncol. 2013;31(13):1690-8.
Zhuang Z, Yang C, Lorenzo F, Merino M, Fojo T, Kebebew E, Popovic V, Stratakis CA, Prchal JT, Pacak K. Somatic HIF2A gain-of-function mutations in paraganglioma with polycythemia. N Engl J Med. 2012;367(10):922-30.
Lu J, Kovach JS, Johnson F, Chiang J, Hodes R, Lonser R, Zhuang Z. Inhibition of serine/threonine phosphatase PP2A enhances cancer chemotherapy by blocking DNA damage induced defense mechanisms. Proc Natl Acad Sci U S A. 2009;106(28):11697-702.
Related Scientific Focus Areas
Genetics and Genomics
This page was last updated on April 14th, 2022