Johns Hopkins University School of Medicine Baltimore, Maryland
Professor of Oncology Sidney Kimmel Comprehensive Cancer Center
Unveiling the molecular links between obesity, the microbiome, and breast cancer and developing strategies to disrupt them.
Obesity is an important risk factor for breast cancer—a five-unit increase in BMI is associated with a 12 percent increase in breast cancer risk. In the United States, about 36 percent of adults are obese based on BMI, while approximately 13 percent of the world population is obese, and the prevalence is increasing globally. Dr. Sharma and her team study the molecular changes induced by obesity that promote breast cancer development, progression, and metastasis. They also focus on the intersections between obesity and the microbiome (the bacteria that reside throughout our body). Many studies found that the complex makeup of the microbiome changes with disease or other alterations to our physiology—like fluctuations in weight—and these changes in bacterial populations may have profound effects on the body. Dr. Sharma’s team is working to unveil how obesity, and obesity-induced changes in the microbiome, may influence breast cancer.
The team’s findings include the presence of a specific bacteria in malignant mammary tumors in laboratory models, Bacteroides fragilis, that promotes breast cancer progression. They also found that high leptin levels (hyperleptinemia) associated with obese state is a major factor in breast cancer growth, metastasis and in cancer initiation. After screening a library of bioactive molecules, they have shown the efficacy of oral regimens of a selection of these compounds in achieving inhibition of breast tumor growth and metastasis in laboratory models. They have also observed an important role of adipocytes, fat cells, in the breast tumor microenvironment and are investigating strategies to abrogate the impact of adipocytes on breast cancer.
Dr. Sharma’s team will continue to examine obesity-driven changes in breast tumor microenvironment to elucidate the underlying molecular mechanisms and develop preventive and therapeutic strategies to reprogram these multifaceted networks. The team has discovered important microbes that promote breast cancer initiation and progression, but microbes with protective effects have also been discovered. Together, these proposed studies will help develop better prevention and treatment strategies.
Dr. Dipali Sharma is a 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.
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. 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.
2011
The GHOST Award
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