Dipali Sharma, PhD
Associate Professor of Oncology
Kimmel Cancer Center
Johns Hopkins University
2013-2014 BCRF Project:
(The Planet Fitness Award)
Approximately 90,000 people die each year from obesity-related cancers. High levels of the protein hormone leptin, a gatekeeper of fat metabolism and characteristic of an obese state, are associated with aggressive cancer progression. The overall goal of Dr. Sharma’s research project is to understand the molecular changes induced by obesity to promote breast cancer development, progression and metastasis, and to develop new strategies for blocking the molecular connection between obesity and breast cancer. Dr. Sharma’s lab has shown that high leptin levels (hyperleptinemia) associated with obese state is a major cause of breast cancer progression and metastasis. After screening a library of bioactive molecules, these investigators selected honokiol, a bioactive compound derived from the bark of magnolia tree. They showed the efficacy of honokiol in achieving inhibition of breast tumor growth and elucidated underlying molecular mechanisms. Recent studies from this team show that honokiol treatment can inhibit leptin-induced growth and the metastatic potential of breast cancer cells. They report that honokiol effectively reverses leptin-induced epithelial-mesenchymal transition and blocks migration/invasion of breast cancer cells in high-leptin conditions. These studies have laid a foundation for the further development of honokiol as an effective agent to disrupt obesity-breast cancer axis.
Dr. Sharma reports that her team has found the molecular signaling axis directly inhibited by honokiol to provide mechanistic insight. These mechanistic observations have also empowered the researchers to examine novel combination therapy regimens. They will further evaluate the molecular crosstalk between honokiol and leptin pathway and identify the key nodes. They will examine the potential of honokiol in preventing breast cancer in obese state.
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.