Dipali Sharma, PhD

2012-2013 BCRF Project:
(made possible by generous support from Planet Fitness)

Approximately 90,000 people die each year from obesity-related cancers. High levels of leptin, characteristic of an obese state, are associated with aggressive cancer progression. Dr. Sharma's overall research goal is to identify targets that can be disrupted to break the obesity-cancer connection. Her team is developing a non-endocrine, non-toxic and effective treatment regimen for inhibition of molecular connection between obesity and breast cancer utilizing honokiol, a bioactive compound derived from the bark of magnolia tree. Preclinical studies have shown that this compound has anti-inflammatory, anti-thrombosis, as well as anti-oxidant properties. Honokiol has also exhibited various anti-cancer functions such as apoptosis induction and growth inhibition in leukemia, multiple myeloma, colorectal, lung cancer and recently breast cancer. Her BCRF-supported project will assess Honokiol's ability to prevent breast cancer.

This research will provide the preclinical data necessary for the successful development of novel leptin antagonists for future translational studies, which can potentially impact a vast majority of breast cancer patients with high leptin levels due to obesity.

Mid-year Progress: Ongoing objective of this research project is to understand the molecular changes induced by obesity to promote breast cancer development, progression and metastasis and to develop a non-endocrine, non-toxic and effective prevention and treatment regimen for blocking the molecular connection between obesity and breast cancer. After screening a library of bioactive molecules, Dr. Sharma selected honokiol, a bioactive compound derived from the bark of magnolia tree. Recent studies from this lab show that honokiol treatment can inhibit leptin-induced growth and metastatic potential of breast cancer cells. These investigators report that honokiol effectively reverses leptin-induced epithelial-mesenchymal transition and blocks migration/ invasion of breast cancer cells. They also found the molecular signaling axis directly inhibited by honokiol to provide mechanistic insight. These studies have laid foundation for the further development of honokiol as an effective agent to disrupt obesity-breast cancer axis.

Bio:
Dr. Sharma is an Associate Professor in the Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. She obtained her doctorate in Molecular Biology and Oncology from the University of Delhi. She then completed fellowships at both the University of Maryland and the Sidney Kimmel Comprehensive Cancer Center training under the mentorship of Dr. Nancy Davidson.

The prevalence of obesity, an epidemic of major proportions in the United States today, has risen steadily over the last several decades. Research on the biological mechanisms underpinning the link between cancer and obesity is clearly a vitally important area, with major implications for both public health and fundamental cancer research. Dr. Sharma focuses on investigating the molecular links between obesity and cancer, emphasizing aspects that have potential clinical significance. Her studies on obesity-related hormones, adipocytokines, showed that leptin promotes the proliferative response and metastatic potential as well as modulates the expression of various genes involved in cell cycle, apoptosis and metastasis. Dr. Sharma is currently examining the potential of adiponectin as an antagonist using innovative approaches including nanotechnology to investigate these important aspects in obesity-breast tumorigenesis connection. She recently showed that adiponectin increases the expression of upstream kinase and tumor suppressor LKB1 and alters AMPK-mTOR-S6K pathway. This discovery has received much attention in the obesity-cancer field and beyond, especially since LKB1 is a master regulator kinase. To get to the bottom of obesity-cancer connection, her lab is exploring the genes, molecules, hormones and cellular processes that could cause and promote cancer in obese people. Using various physiologically relevant models and cell lines, their aim is to find molecular targets that can be disrupted to break the obesity-cancer axis. She is exploring new strategies to disrupt the obesity-cancer connection using novel small molecule inhibitors as well as bioactive food components. Her overall goal is to understand the molecular networks by which obesity affects carcinogenesis and discover novel agents to effectively disrupt obesity-cancer axis.