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Dipali Sharma, PhD
Professor of Oncology
Kimmel Cancer Center
Johns Hopkins University, School of Medicine
Goal: To understand the molecular links between obesity and breast cancer and develop new strategies to counter these changes.
Impact: Dr. Sharma is exploring the genes, molecules, hormones, and cellular processes that may cause and promote cancer in obese people. Her work may lead to novel natural approaches that could potentially lower the risk of breast cancer.
What’s next: She and her team will continue to examine obesity-driven changes in breast tumor microenviroment, with a special emphasis on fat cells, microbiome, and metabolite levels.
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 are 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: Dr. Sharma has shown that an obesity-related condition known as hyperleptinemia is a major factor not only in breast cancer progression and metastasis but also in cancer initiation. It also appears to interfere with tamoxifen efficacy.
Additionally, using meta-analyses, she and her colleagues studied dysbiosis—a microbial imbalance or maladaptation on or inside the body—in breast cancer patients. They identified key changes in the microbiome and performed detailed molecular and functional analyses of key bacteria and their metabolites. They also observed distinct changes in microbiota—the variety of bacteria, viruses, fungi, and other single-celled animals that live in the body—in the obese state.
What’s next: Dr. Sharma will continue to study the link between the microbiome and tumor microenvironment.
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.