Jin-Rong Zhou, PhD
Associate Professor of Surgery, Harvard Medical School
Director, Nutrition/Metabolism Laboratory, BIDMC
Hamid Abdolmaleky, MD
Reza Alam, MD
Lixia He, PhD
Sheng Yin, PhD
The long-term goal of my research is to define efficacious and safe nutritional and bioactive regimens for the prevention and therapy of cancer and other metabolic disorders. My laboratory has focused on evaluating the efficacy and safety of several bioactive natural compounds on the growth, progression, and metastasis of certain types of cancer in both in vitro and in vivo model systems, and investigating the mechanisms of action of these bioactive components. Since cancer stem cells are recognized to be responsible for drug resistance and metastasis of cancer, our special effort has been in identifying bioactive components for targeting cancer stem cells. Additionally, we have investigated the effects of bioactive components on blood glucose management, alleviation of chronic kidney disease, and prevention of autism. In the past year, my laboratory has focused on the following projects.
Tanshinones as potent anti-cancer and anti-cancer stem cell agents by targeting Aurora A and B kinases
Our studies have shown that tanshinones, which include cryptotanshinone (CT), tanshinone I (T1), and tanshinone IIA (T2A), have potent anti-proliferation and anti-cancer stem cell (CSC) self-renewal activities against several types of cancer cell lines. Further investigations showed that, among these tanshinones, T1 had the most potent activities and inhibited the growth of prostate tumors and lung tumors in animal models, with minimal side effects. Further mechanism studies demonstrated that downregulation of Aurora A and B kinases was an important mechanism shared by all three tanshinones. To further improve the anti-cancer activities of bioactive agents with additive and/or synergistic combination, our studies showed that the combination between CT and T1 or T2A had synergistic effect against prostate cancer in part via downregulation of aurora kinases, whereas the combination of T1 and T2A had an antagonistic effect associated with upregulation of aurora kinases. Our other studies also showed that T1 and resveratrol combination had a synergistic effect on inhibiting prostate cancer, in part via downregulation expression of aurora A and c-myc in a combined manner. We are in the processing to verify the efficacy of these synergistic combination regimens in clinically relevant animal models of cancer.
Bioactive components delay the development and progression of chronic kidney injury by inhibiting inflammation
We have also studied the effects of bioactive components, activated lactic acid (ALA), and a soy germ extract (SGE), on chronic kidney disease in vitro and in vivo. Both ALA and SGE showed anti-inflammatory and oxidative stress-suppressing activities in kidney cell models in vitro. Further in vivo study also showed the preventive efficacy of ALA or SGE on an adenine-induced chronic kidney injury animal model by inhibiting inflammation and reducing toxicity in the kidney that was associated with modulating inflammation biomarkers in blood and kidney samples. Additionally, these bioactive components had minimal side effect in vivo, supporting that these bioactive components may warrant further investigation for potential clinical application.
Anti-inflammatory effect of bioactive components for prevention of autism
In this research project, we have successfully established the iPSC-differentiated neuronal and astrocitic cell models for identifying active components and for mechanism studies. Our studies showed that autistic iPSC-derived astrocytes had significantly increased inflammation levels, compared with that of the normal controls. Using this novel cell model, we have identified several candidate bioactive agents that showed potent anti-inflammation activities in astrocytes. We are in the process of further verifying the in vivo efficacy to elucidate mechanisms of action of bioactive agents.
Grant Review Activities
- Review panel, Key Programs, National Science Foundation of China, 2017
- Review panel, General Research Fund, Research Grant Council, Hong Kong, 2017
- Ad hoc member, SEP-3 for Provocative Questions, NCI/NIH, 2017
- Review panel, Function and Efficacy of Nutrients Review Panel of National Institute of Food and Agriculture (NIFA), US Department of Agriculture (USDA), 2017
- Ad hoc manuscript reviewer: eight scientific journals
- Editorial board members: Health; Digital Chinese Medicine; Journal of Genetic, Molecular and Cellular Biology; Journal of Disease and Global Health; Single Cell Biology; World Journal of Clinical Oncology; International J. Tropical Disease & Health
- Editor: Frontiers in Biosciences
- Editor-in-Chief: Nutrition and Metabolic Insights (2012-present), Journal of Health Sciences (2013-present)
- Precision Medicine: Challenges and Opportunities; Jiangsu Oncology Medical Quality Control Center Annual Meeting/Cancer Chemotherapy Conference, Nanjing, China, 2016
- Soybeans for prevention of breast cancer: epidemiological associations and experimental evidence; 1st ICC Asia-Pacific Grains Conference, May 21-24, 2017, Xiamen, China, 2017
- Nutritional strategies to delay metastatic recurrence in cancer survivors; 13th China Nutrition Science Congress, Beijing, China, 2017
- Nutrition and Cancer Prevention; Center for Agro-Products Processing, Institute of Food Science and Technology, Chinese Agricultural Academy of Sciences, Beijing, China, 2017
- Target on cancer stem cells by natural bioactive components against metastatic recurrence; Food Safety and Technology Research Centre, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China, 2017
- Soybeans for prevention and therapy of breast cancer: beneficial or harmful?; Specialty Committee of Breast Diseases of World Federation of Chinese Medicine Societies Annual Meeting, Shanghai, China, 2017
- Chair, Diet & Cancer Research Interest Group, American Society of Nutrition, 2017
- Co-Chair, Diet and Cancer: Molecular and Cellular Targets Section, Experimental Biology Annual Meeting, Chicago, IL, 2017
- Chair, Nutrition and Chronic Diseases Section, 13th China Nutrition Science Congress, Beijing, China, 2017
- Member, Organizing Committee, 3rd World Congress on Cancer and Prevention Methods, Barcelona, Spain, 2017
- Vice Chairperson, The 1st Board of Specialty Committee of Breast Diseases, World Federation of Chinese Medicine Societies
- Distinguished Medical Expert, Jiangsu Provincial Commission of Health and Family Planning, China, 2016-2018
Teaching, Training, and Education
I have been training post-doctoral fellows on a daily basis for the past year. In addition, I served as the co-supervisor of graduate students and thesis defense committee member at the Nanjing University of Chinese Medicine, China, and at the Institute of Food Science Research, Spain.
Selected Research Support
Maternal anti-inflammatory diet for prevention of autism in offspring; Allen Foundation, 2015-2017; PI: Jin-Rong Zhou, PhD
Effects of bioactive agents on prevention of chronic kidney disease; Nichimo Biotics Co. and Lifetrade Co., Japan, 2015-2018; PI: Jin-Rong Zhou, PhD
Effects of Epimedium flavonoids extract (EFE) on osteoporosis and breast cancer; Kanion Pharmaceutical Co., China, 2017-2020; PI: Jin-Rong Zhou, PhD
Nutraceuticals for diabetes management: Efficacy evaluation and mechanism elucidation; Feihe Nutrition Laboratory, BIDMC, 2016-2018; PI: George Blackburn, MD, PhD/Elliot Chaikof, MD, PhD (Co-Investigator: Jin-Rong Zhou, PhD)
Wang S, Shen P, Zhou J, Lu Y. Diet phytochemicals and cutaneous carcinoma chemoprevention: A review. Pharmacology Research 2017;119:327-46.
del Castillo MD, Iriondo-DeHond A, Martinez-Saez N, Fernandez-Gomez B, Iriondo-DeHond M, Zhou J-R. Applications of recovered compounds in food products. In Handbook of Coffee Processing By-Products: Sustainable Applications. Edited by C. Galanakis, Eselvier, 2017;Chapter 6, pp 171-194.
Alam R, Abdolmaleky HM, Zhou J-R. Microbiome, inflammation, epigenetic alterations, and mental diseases. Am J Med Genet B Neuropsychiatr Genet 2017;174:651-60.