Our Research
Research in this laboratory aims to better understand the fundamental mechanisms that control apoptosis (a cell self-killing mechanism) and autophagy (a cell self-eating process). The ultimate goal of Dr. Wang’s research is to translate basic science discoveries to the development of new approaches for the treatment and prevention of cancer.
Human melanoma cells expressing mRFP-EGFP-LC3 were deprived of nutrients to induce autophagy. LC3 localizes to autophagosomal membranes during autophagy. As EGFP is quenched in the acidic environment upon lysosomal fusion, autophagosomes and autolysosomes are represented as yellow (RFP+; EGFP+) or red (RFP+; EGFP-) puncta, respectively.
Autophagy in Cancer
Autophagy (“self-eating”) is a cellular recycling process in which damaged proteins and/or organelles (i.e. “garbage”) are engulfed by double-membrane vesicles (i.e. “recycling trucks”) and delivered to the lysosome (i.e. “the recycling plant”) for degradation and recycling. Normal cells undergo autophagy as a house-keeping function to maintain the health of the cell.
Transformation is the process by which a normal cell changes to a cancer cell. Cancer cells possess two main abnormalities: 1) uncontrolled growth and 2) resistance to self-killing by apoptosis. Autophagy has important roles in transformation as well as cancer progression and response to cancer therapy.
During transformation, cells gain the ability to proliferate independent of external or internal cues. The rapid proliferation can trigger a “self-killing” process known as apoptosis to eliminate the “abnormal” cells and prevent further transformation. In addition, much as though a highly populated city generates more garbage, the rapidly proliferating cells produce more waste. Autophagy acts as a “self-repair” mechanism that attempts to remove the waste and restore the cell back to normal function, thus serving as a tumor suppressor.
If the rapidly proliferating cells acquire additional DNA mutations so that they can no longer self-repair by autophagy or self-kill by apoptosis, the cells transform to cancer cells.
Autophagy fuels the growth of cancer cells by providing nutrients and building blocks to the dividing cells. This is critical because the dense tumor environment makes it difficult for the cells to take up nutrients from the bloodstream. In addition, autophagy is induced in response to cancer therapies (e.g. targeted therapies, radiation, and chemotherapy) as a survival mechanism to eliminate the toxic materials generated by the therapies. Therefore, autophagy also functions as a tumor promoter.
Our Research
Our lab has a broad interest in understanding the molecular mechanisms of tumor cell survival and identifying targets for anticancer therapy. Some of the current questions that we are investigating include:
- What are the molecular mechanisms for phagophore elongation and closure?
- How should we target autophagy for cancer therapy?
- Why are some tumors more susceptible to autophagy inhibition than others, and what biomarkers can be used to identify these patients for personalized medicine?
- How does autophagy regulate extracellular vesicle secretion and tumor metastasis?
- What are the molecular mechanisms of drug resistance to targeted therapies in pediatric acute myeloid leukemia (AML), and how can we effectively target the vulnerabilities of drug-tolerant cells?
Our research is currently focused on the following areas:
Molecular Regulators of Autophagy
Targeting Autophagy in Cancer
Pediatric Acute Myeloid Leukemia
Recent Publications