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Dipali Sharma, PhD
Professor of Oncology
Kimmel Cancer Center
Johns Hopkins University
Goal: To understand the molecular links between obesity and breast cancer and to develop innovative bioactive strategies to counter these changes.
Impact: Obesity is an important risk factor for breast cancer, and the prevalence of obesity is increasing globally. Dr. Sharma is investigating the effect of obesity on the microbiome and metabolome (small chemicals produced during metabolism) to better understand its impact on breast cancer progression. By providing a greater understanding of the molecular underpinnings of the obesity-breast cancer connection her work has the potential to impact a growing population of obese individuals who may be at risk of developing breast cancer.
What’s next: Dr. Sharma identified key changes in the microbiome in breast cancer patients and performed detailed analyses of key bacteria and their metabolites. She is now working toward revealing the link between the microbiome and the tumor environment (non-tumor cells, such as fat cells and immune cells, along with breast tumor cells) and testing bioactive molecules to reprogram the obese-microbiome.
Obesity is a risk factor for many types of cancer, including breast cancer after menopause, so it’s crucial to understand this relationship in order to develop better prevention strategies. Dr. Sharma is investigating how specific microbiome changes in those who are obese can impact breast cancer progression, which may inform the development of strategies to combat the molecular effects of these microbial alterations.
Full Research Summary
Research goal: Understanding the molecular underpinnings of the obesity-breast cancer connection and developing strategies to break it.
Impact: Obesity is an important risk factor for breast cancer, and the prevalence of obesity is increasing globally. Approximately 13 percent of the world population is obese; in the United States, about 36 percent of adults are obese. A 5-unit increase in BMI is associated with a 12 percent increase in breast cancer risk. Dr. Sharma aims to determine the molecular changes induced by obesity that promote breast cancer development, progression, and metastasis, and develop new strategies to counter these changes.
Current investigation: She and her team have been testing Honokiol, a bioactive compound derived from the bark of magnolia trees, which appears to inhibit breast tumor growth and metastasis in those
with high leptin levels (hyperleptinemia), which is associated with obesity. They have also been studying adipocytes (fat cells) in the breast microenvironment and how they impact breast tumor progression and are evaluating various strategies to evade the impact of adipocytes on breast cancer.
What she’s learned so far: Using meta-analyses, Dr. Sharma and her team studied microbial imbalance in breast cancer patients and identified key changes in the microbiome. They performed detailed molecular and functional analyses of key bacteria and their metabolites and observed distinct changes in microbiota in obesity.
What’s next: Dr. Sharma will continue investigating whether orally administered Honokiol can be a bioactive approach to inhibit breast cancer growth. She and her team will also work toward elucidating the link between the microbiome and the tumor microenvironment (adipocytes, macrophages, and breast cancer cells) and evaluating bioactive strategies to reprogram the obese-microbiome.
Dr. 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, Johns Hopkins.
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.