Research Focus

Throughout history, natural products have been a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. The research interests of Dr. Chang are on the isolation, characterization, and biological evaluation of natural products of higher plant origin and microbes. Her long-term goal is to identify leads and compounds derived from natural products that are active against cancer and/or inflammation. Her research project will be performed through collaborations between different disciplines at the UH Cancer Center to guide the identification of natural products as anticancer drug leads.

Dr. Chang has worked on the Signal Transducer and Activator of Transcription Factor (STAT)3 inhibitors as cancer chemotherapeutic targets in the past. It is widely accepted that chronic inflammation plays a key role in cancer. Nuclear factor kappa B (NF-κB), an inducible transcription factor, is responsible for different cellular responses like the regulation of expression of pro-inflammatory cytokines and cell cycle-regulatory components. Abnormal NF-κB upregulation may play vital roles of inflammation-induced carcinogenesis. The central role of NF-κB in those pathologies makes it a target for the treatment of inflammatory diseases such as cancer. Currently, her work focuses on targeting the aberrant NF-κB pathways (UH Cancer Center collaborator, publications and a US patent). Her team is also interested in Thioredoxin reductase (TrxRs) as a potential chemotherapeutic target for anticancer drug development. TrxR isoform 1 have been observed in various malignancies including lung and hepatocellular carcinomas than in normal tissues.

Currently, Dr. Chang's team is studying Vernonia cinerea, Physalis peruviana (poha berry), Waltheria indica (ʻuhaloa), Osteomeles anthyllidifolia (ʻūlei), and a few native Hawaiian healing plants with potential anticancer activity. Her team is also evaluating the potential of Hawaiian medicinal plants as anticancer leads. The crude organic extract from the whole poha plant has anti-inflammatory activity in vitro, having shown inhibition of MDA-MB-231 breast cancer cells. The identification of bioactive lead compounds from these plants is underway. Waltheria indica is often used in Hawaiian traditional medicine to treat throat ailments, cough and respiratory infections. The extract and compounds exhibited significant inhibitory activity on TNF-α induced NF-κB activation at 20 µg/mL in Luc-HEK293 cells percentages inhibition in the range of 46.5-92.9%. In particular, a series of natural products (lignanoids and alkaloids) are isolated from Waltheria indica.

Dr. Chang has several papers published in this area, and a US Patent (PCT/US14/043523) and provisional disclosures with collaborators.