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Senthil Muthuswamy, PhD
Director, Program in Cell Biology,
Beth Israel Deaconess Medical Centre,
Associate Professor, Department of Medicine,
Harvard Medical School
Seeking to advance vaccine development in breast cancer.
Laboratory studies are conducted to explore novel therapeutic strategies and vaccine development to improve the treatment and prevention of metastasis.
These studies may lead to advancements to benefit patients with advanced breast cancer and those at high risk of developing invasive breast cancer.
Resistance to anti-estrogen (endocrine) therapies is a persistent clinical challenge and new treatments are urgently needed to prevent these tumors from progressing and spreading to other tissues. Dr. Muthuswamy is pursuing groundbreaking research that may provide new treatment and prevention options.
Tissue architecture is a critical component in organ function and health. A key factor in maintaining tissue architecture are a class of proteins called polarity proteins. While these proteins are typically viewed as tumor suppressors for their role in maintaining tissue architecture, Dr. Muthuswamy's team discovered an unexpected tumor-promoting role of polarity proteins through direct action on tumor cell growth and altering immune cell function.
In their BCRF project, the team will exploit these insights and determine whether these proteins may be candidates for drug development for breast cancer patients with metastatic, estrogen receptor-positive breast cancer. They are pursuing two separate but related studies.
In one study, they will explore whether targeting a polarity protein called LLGL2 can prevent tumor formation in laboratory models of endocrine-resistant, metastatic disease. The second study builds on the discovery of a novel function of another polarity protein called SCRIB in regulating immune function.
They hope information obtained from this work will lead to the development of a personalized breast cancer vaccine. Although therapeutic vaccination is proving to be successful for patients with a type of leukemia, it has not been successful for breast cancer.
Dr. Muthuswamy’s team believes they can develop effective breast cancer vaccines for both advanced cancers and for pre-malignant disease to prevent progression. These two complimentary approaches may benefit patients with metastatic disease and prevent cancer development in patients with high-risk premalignant disease.
Senthil K. Muthuswamy, Ph.D., is the Director of the Cell Biology Program at the Cancer Centre at Beth Israel Deaconess Medical Centre, Harvard Medical School. Dr. Muthuswamy received his Ph.D. from McMaster University, Canada and did his postdoctoral fellowship with Joan Brugge at Harvard Medical School. He began his independent faculty position at Cold Spring Harbor Laboratory, New York and subsequently moved to Princess Margaret Cancer Centre as the Margaret Lau Chair in Breast Cancer Research. In 2015, he moved to BIDMC to direct the Cell Biology program at the Cancer Center at BIDMC. Dr. Muthuswamy is a recipient of Rita Allen Scholar award, V Foundation scholar award, US Army Era of Hope Scholar Award, and the Canadian Society of Biochemistry and Molecular & Cellular Biology young scientist award for outstanding research achievements.
His laboratory pioneered both the development and use of three-dimensional culture methods for modeling carcinoma of breast and pancreas and understanding the unexplored role played by cell polarity proteins in regulating the biology of cancer. He was the first to identify cell polarity proteins, such as PARD6, PARD3 and SCRIB, as critical regulators of cell death, cell proliferation and metastasis either by themselves or in cooperation with oncogenes, such as ERBB2 and MYC, in breast cancer. His group continues to investigate and discover how cell polarity proteins regulate cell biology of cancer and normal cells and its impact on stress adaptation and therapy resistance.
He recently launched a new initiative in his lab to bridge cancer biology and clinical cancer care, called “Microscope to Stethoscope”. His team is developing and implementing personalized tumor organoid culture platforms to assist patients and oncologists by performing a lab-based screen of available treatment options to identify the best possible cancer treatment for each patient. This effort is married to his long-standing interest in using patient-derived tumor models for translational and discovery research to find better cancer treatments.