Cancer is a remarkably heterogenous disease at all aspects. This complexity represents one of the major challenges to develop precise diagnoses and effective treatments. As such, we work toward a better understanding of cancer heterogeneity and subsequently better therapeutic approaches.

1. Cancer Stem Cells.
Over the past decade, cancer cell subpopulations with stem cell-like characteristics are identified in a wide range of human cancers, including glioma. These cells are named cancer stem cells or cancer initiating cells. Cancer stem cells have extended capacity of self-renewal and can give rise to multiple lineages of differentiated progenies. Cancer stem cells in glioma and several other cancer types exhibit preferential resistance toward conventional chemoradiotherapy and targeted therapies. Therefore, these cells are blamed to produce recurrent tumors. Our laboratory has a specific interest in the mechanisms that mediate resistance to radiation and other therapeutics in glioma stem cells. To this end, we are currently working on the Notch signaling pathway and other targets to develop glioma stem cell-targeted strategies.

2. Personalized Medicine.
The oncogene addiction model describes the dependence of certain cancers on the products of one or a few oncogenes. This model represents the paradigmatic and most successful rationale for targeted cancer therapy, which has led to remarkable clinical success in some molecularly defined subsets of cancers, such as BCR-ABL-driven chronic myelogenous leukemia, EGFR-mutated non-small cell lung cancer, and so on. With rapidly evolving new technology, the Cancer Genome Atlas (TCGA) project and other studies have greatly improved our understanding of the genetic landscape of human cancers. Through multi-institutional collaborations, we have collected a large panel of patient-derived glioblastoma samples. We are working with other groups to characterize the genome and epigenome of these samples. On the basis of this platform, we are now working to identify novel links between tumor genotypes and phenotypes with a goal to develop molecular-guided treatments.

3. Epigenetic therapy.
Our genetic information is packed in chromatins. Epigenetics include all chromatin-based events that are essential for translating genetic information into cellular functions. It has become increasingly recognized that epigenetic abnormalities are critically implicated in cancer initiation and progression. Recurrent mutations altering epigenetic regulation are increasingly identified in human cancers, including glioblastoma (e.g. IDH1/2, histone H3). Strikingly, the most recent TCGA study shows that nearly half of glioblastoma tumors carry at least one mutation that affects an epigenetic regulator. We recently identified crucial functions of the BET family bromodomain proteins in proliferation and survival of glioblastoma with diverse genetic profiles. The BET proteins are epigenetic readers that specifically bind to acetylated histones and direct active transcription. Inhibition of BET proteins by small molecular inhibitors or shRNA shows that BET proteins are implicated in transcription of many important oncogenes. As such, targeting BET bromodomain proteins is expected to generate broad anti-neoplastic effects in glioblastoma and many other cancer types. On the basis of these findings, we want to develop more effective combinations that can improve FDA-approved drugs or drugs currently in pipeline. We are also interrogating the role of BET bromodomain proteins in other cancer types based on some key targets genes that we have identified.


The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. LZAP: A break on phosphorylation. Wang J (2017) Cell Cycle 16(19): 1737-1738
    › Primary publication · 28118073 (PubMed) · PMC5965456 (PubMed Central)
  2. The MAPK Pathway Regulates Intrinsic Resistance to BET Inhibitors in Colorectal Cancer. Ma Y, Wang L, Neitzel LR, Loganathan SN, Tang N, Qin L, Crispi EE, Guo Y, Knapp S, Beauchamp RD, Lee E, Wang J (2017) Clin Cancer Res 23(8): 2027-2037
    › Primary publication · 27678457 (PubMed) · PMC5368030 (PubMed Central)
  3. BET bromodomain inhibitors suppress EWS-FLI1-dependent transcription and the IGF1 autocrine mechanism in Ewing sarcoma. Loganathan SN, Tang N, Fleming JT, Ma Y, Guo Y, Borinstein SC, Chiang C, Wang J (2016) Oncotarget 7(28): 43504-43517
    › Primary publication · 27259270 (PubMed) · PMC5190040 (PubMed Central)
  4. Bone morphogenetic protein signaling promotes tumorigenesis in a murine model of high-grade glioma. Hover LD, Owens P, Munden AL, Wang J, Chambless LB, Hopkins CR, Hong CC, Moses HL, Abel TW (2016) Neuro Oncol 18(7): 928-38
    › Primary publication · 26683138 (PubMed) · PMC4896540 (PubMed Central)
  5. InsR/IGF1R Pathway Mediates Resistance to EGFR Inhibitors in Glioblastoma. Ma Y, Tang N, Thompson RC, Mobley BC, Clark SW, Sarkaria JN, Wang J (2016) Clin Cancer Res 22(7): 1767-76
    › Primary publication · 26561558 (PubMed) · PMC4818693 (PubMed Central)
  6. Insulin-mediated signaling promotes proliferation and survival of glioblastoma through Akt activation. Gong Y, Ma Y, Sinyuk M, Loganathan S, Thompson RC, Sarkaria JN, Chen W, Lathia JD, Mobley BC, Clark SW, Wang J (2016) Neuro Oncol 18(1): 48-57
    › Primary publication · 26136493 (PubMed) · PMC4677408 (PubMed Central)
  7. Critical functions of RhoB in support of glioblastoma tumorigenesis. Ma Y, Gong Y, Cheng Z, Loganathan S, Kao C, Sarkaria JN, Abel TW, Wang J (2015) Neuro Oncol 17(4): 516-25
    › Primary publication · 25216671 (PubMed) · PMC4483068 (PubMed Central)
  8. Cancer stem cells in glioma: challenges and opportunities. Wang J, Ma Y, Cooper MK (2013) Transl Cancer Res 2(5): 429-441
    › Primary publication · 24634854 (PubMed) · PMC3952560 (PubMed Central)
  9. JNK signaling mediates EPHA2-dependent tumor cell proliferation, motility, and cancer stem cell-like properties in non-small cell lung cancer. Song W, Ma Y, Wang J, Brantley-Sieders D, Chen J (2014) Cancer Res 74(9): 2444-54
    › Primary publication · 24607842 (PubMed) · PMC4008716 (PubMed Central)
  10. Inhibition of BET bromodomain targets genetically diverse glioblastoma. Cheng Z, Gong Y, Ma Y, Lu K, Lu X, Pierce LA, Thompson RC, Muller S, Knapp S, Wang J (2013) Clin Cancer Res 19(7): 1748-59
    › Primary publication · 23403638 (PubMed) · PMC4172367 (PubMed Central)
  11. LZAP, a putative tumor suppressor, selectively inhibits NF-kappaB. Wang J, An H, Mayo MW, Baldwin AS, Yarbrough WG (2007) Cancer Cell 12(3): 239-51
    › Primary publication · 17785205 (PubMed)