The focus of Dr. Zhou's research is the discovery and characterization of small molecule natural products that regulate hypoxia signaling in mammalian cells. Hypoxia (decrease in oxygen tension) occurs under a number of pathological conditions and can affect a variety of organs that range from the brain to the heart. Our current research is to discover and characterize small molecule natural product regulators of hypoxia-inducible factors (HIFs), transcription factors that regulate cellular adaptation and survival under hypoxic conditions.

The three major components of our research are:
1) cell-based screening of natural product-rich extracts and pure compounds for regulators of HIF activities;
2) molecular characterization of natural product-based HIF regulators, identified through bioassay-guided isolation and structure elucidation;
3) investigation of cellular oxygen sensing and hypoxia signaling, employing natural products as molecular probes.

Using this natural product chemistry-based approach, we have discovered an array of small molecule natural products that regulate HIF activities. Current projects are aimed at the molecular investigation of these natural products. This research employs a combination of biochemical, cell biological, and molecular biological methods. Funding for our research is provided by NIH/NCI, NOAA, and the DOD.

"Samples" of Ongoing Research

 Figure 1.  Characterization of a novel inhibitor (compound 1) of mitochondrial electron transport chain complex I.

Copyright Yu-Dong Zhou 2009.

 Figure 2.  Methylalpinumisoflavone (compound 2) and rotenone (compound 3) inhibit hypoxia-stimulated tumor angiogenesis in vitro.

Figure 3.  Compound 1 inhibitis HIF-1 activation by blocking the induction of nuclear HIF-1a protein.

Copyright Yu-Dong Zhou 2009.