Associate Professor of Oncology
Kimmel Cancer Center
Johns Hopkins University, School of Medicine
Seeking to understand the molecular changes caused by obesity that promote breast cancer and to develop new strategies to counter these changes.
Laboratory studies are ongoing to characterize the chemo-preventive effect of a natural chemical from magnolia trees that inhibits the pro-tumor environment associated with obesity.
These studies could lead to a natural approach that could potentially lower the risk of breast cancer.
Obesity is a known risk factor for post-menopausal breast cancer and is associated with worse outcome in breast cancer patients at any age, but the reasons for this are poorly understood. Dr. Sharma's team is studying how molecular changes caused by obesity promote breast cancer development, progression, and metastasis, with the goal of developing new preventive strategies.
Her work has shown that fat cells and cancer cells talk to each other, leading to a vicious cycle that promotes the release of pro-cancer cytokines (chemicals released by fat cells) and inflammatory molecules. Her studies further suggest that leptin, a protein found at high levels in obese individuals, is a major cause of breast cancer initiation, progression, and metastasis. Conversely, adiponectin, a protective cytokine secreted from fat cells, can cause a natural cell death in breast cancer cells.
In laboratory studies, Dr. Sharma showed that a natural compound called honokiol, found in the bark of magnolia trees, prevents leptin-induced cancer growth and metastatic potential of breast cancer cells. Recent studies from Dr. Sharma’s lab show the potential of honokiol in inhibiting stem cell-like behavior in breast cancer cells, an aggressive characteristic which is strengthened in the presence of high leptin levels.
In the coming year, the team will continue to evaluate the molecular crosstalk between honokiol and the leptin pathway to determine whether honokiol may be effective in preventing obesity-related breast cancer.
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. 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.