Dr. Erxi Wu's Lab

Research Goals

The Wu’s lab focuses on four areas:

1. Cancer (brain tumors, neuroblastoma, pancreatic cancer, etc.) therapeutics targets, cancer stem cell biology
3. Drug binding targets, drug discovery, and natural products
4. Blood biomarkers in cancer and other diseases
5. Therapeutics of neurodegenerative diseases

Identification of novel anti-cancer agents for cancers
We have investigated natural products as anticancer agents for more than two decades. We first used the bioactivity-directed strategy to identify the active compounds for anticancer activity. We further studied these compounds using modern technologies such as molecular biology, and functional genomics, proteomics, etc. to study their efficacy and mechanism in vitro and in vivo. We found that these active compounds can effectively induce cancer apoptosis and cell cycle arrest via various molecular mechanisms. In addition, we take novel approaches to identify the binding targets of these active compounds and other promising anticancer agents in the cells, e.g., we are the first to identify nucleolin as a functional binding protein for salinomycin in neuroblastoma and found that salinomycin may overcome the gemcitabine therapy resistance in pancreatic cancer.

New platform for early detection and prognosis for glioblastoma multiforme (GBM)
We have established a platform for blood biomarker study by using global gene expression profiling of peripheral whole blood. Poor survival of GBM patients (~14.6 months) may result from delayed diagnosis, which typically occurs after individuals display neurological symptoms and require expensive diagnostic magnetic resonance imaging analyses. However, prognoses for patients with low-grade tumors are better than patients with high-grade tumors. Thus, there is a critical unmet need for early cost-effective diagnosis of GBM so that appropriate and potentially life-saving treatment can be initiated before the tumor has progressed and/or neurological function has been impaired. Whole blood is an attractive medium for the identification of disease biomarkers because of its critical roles in immune response, metabolism, communications with cells, and formation of extracellular matrices in various tissues and organs throughout the human body, as well as the simplicity and less invasive nature of sample collection.

Mechanistic studies in medulloblastoma (MB) progression and metastasis
We recently found that the omega-3 fatty acid, docosahexaenoic acid (DHA), and the cancer chemotherapeutic drug etoposide synergistically inhibit MB cell proliferation and induce cell death accompanied with a marked reduction in the expression of CD44 standard form (CD44s). Through collaboration with Dr. Michael Taylor’s laboratory at The Hospital for Sick Children, Toronto, Canada, we found that MB patients having elevated levels of CD44 had poorer outcomes. Additionally we showed that PDGFRβ instead of PDGFRα is a therapeutic target for MB because knockdown of PDGFRβ, but not PDGFRα almost completely eliminated CD44 expression. These findings support our hypothesis that CD44s and PDGFRβ play an important role in MB progression and metastasis.

Novel α-synuclein (α-Syn) pathology and mouse models in synucleinopathies
We have made several novel α-Syn pathological findings in synucleinopathies with my postdoctoral research associates. It recently indicates that Parkinson’s disease (PD) pathology may originate in the vagal nerves from the gut and propagate to the brain. However, less is known about that of multiple system atrophy (MSA), a fatal adult-onset neurodegenerative disorder without effective therapy. Both PD and MSA belong to synucleinopathies. Recently, we show that MSA has different physiological homeostasis and molecular pathways from PD. Thus, we have broadened the landscape of the physiological homeostasis and molecular pathways of synucleinopathies. We found that misfolded α-synuclein (α-Syn) aggregates indeed exist in detrusor or external urethral sphincter in MSA patients.