Department of Cancer Biology and Genetics
914 Biomedical Research Tower
460 W. 12th Avenue
Columbus, OH 43210
Ph: (614) 247-2792
The long-term interest of the lab is to understand the impact of physical environment and mental state on physiological processes and disease pathology and the underlying mechanisms. We have recently reported how an enriched environment not only improve brain function and resiliency, but also affect the body’s overall state of health. Our mechanistic studies led to the characterization of a novel brain-fat axis, the hypothalamic-sympathoneural-adipocyte axis (HSA) and the development of molecular therapy for obesity and diabetes. These findings provide insights on how one’s living condition, social contact, life style can efficiently influence brain activity (cognition, stress, mood etc) and how these changes in brain interact with other systems (fat, endocrine, immune systems, etc) both at the molecular level and at the systemic level to influence the metabolism and various diseases such as obesity, diabetes, and cancer through a central mechanism.
The Programmatic Theme of research: how environmental stimuli to the CNS shape biological processes and disease pathology; how this knowledge can be harnessed to improve health and treat diseases. Our current research intends to further define the HSA axis, and pursue therapeutic potentials including gene transfer to the hypothalamus and genetic or pharmacological modulation of adipose tissue. Specifically, one major project studies the preventive and therapeutic effects of HSA axis activation in cancer and obesity. The second project attempts to understand how eustress (environmental enrichment) and distress (social isolation) trigger distinct molecular changes in the brain that lead to differential effects on cancer. The third project seeks to understand the role of HSA axis in healthy aging to identify interventions to combat the chronic diseases of aging, many of which are associated with alterations in fat metabolism. The fourth project investigates the subset of obesity (human adenovirus type 36 infection) that is insulin sensitive and metabolically healthy, and explores the possibility of creatively using viruses for beneficial purposes in the treatment of metabolic syndromes and cancer. Furthermore we have developed a novel anxiety/depression mouse model completely based on perception and are investigating the mechanisms. Additional projects seek to understand how environments may program brain circuits during adolescence leading to long-term impact on health and disease in adulthood. Several exploratory projects include: how the environment influences type 1 diabetes via modulating emotionality and immune system; what is the interaction between environment and diet and its effects on obesity/cancer risk; how to manipulate brain or fat to prevent or treat cancer cachexia.
1. Liu, X, McMurphy, T, Xiao, R, Slater, A, Huang, W, Cao, L. (2014). Hypothalamic gene transfer of BDNF inhibits breast cancer progression and metastasis in middle age obese mice. Molecular Therapy Epub ahead of print. dio: 10.1038/mt.2014.45
2. Liu, X, Magee, D, Wang, C, McMurphy, T, Slater, A, During, M, Cao, L. (2014). Adipose tissue insulin receptor knockdown via a new primate-derived hybrid recombinant AAV serotype. Molecular Therapy-Methods & Clinical Development 1, 8; doi:10.1038/mtm.2013.8
3. McMurphy, T, Xiao, R, Magee, D, Slater A, Zabeau, L, Tavernier, J, Cao, L. (2014) The anti-tumor activity of a neutralizing nanobody targeting leptin receptor in a mouse model of melanoma. Plos One 9 (2):e89895. Doi: 10.1371/journal.pone.0089895. PMID: 24587106
4. Cao, L*, During, MJ. (2012). What is the brain-cancer connection? Annu Rev Neuorsci 35, 331-345. PMID: 22462541 (* corresponding author)
5. Cao, L*, Choi, EY, Liu, X, Martin, A, Wang, C, Xu, X, During, MJ. (2011). White to brown fat phenotypic switch induced by genetic and environmental activation of hypothalamic-adipocyte axis. Cell Metabolism 14, 324-338. PMID: 21907139 (* corresponding author)
6. Cao, L*, Liu, X, Lin, EJ, Wang, C, Choi, EY, Riban, V, Lin, B, During, MJ. (2010) Environmental and genetic activation of a brain-adipocyte BDNF/Leptin axis causes cancer remission and inhibition. Cell 142, 52-64. PMID: 20603014 (* corresponding author)
7. Cao, L, Lin, EJ, Cahil,l MC, Wang, C, Liu, X, During, MJ. (2009) Molecular therapy of obesity and diabetes by a physiological autoregulatory approach. Nature Medicine. 15, 447-54. PMID: 19270710.
8. Cao, L, Jiao, X, Zuzga, DS, Liu, Y, Fong, DM, Young, D, During, MJ (2004) VEGF links hippocampal activity with neurogenesis, learning and memory. Nature Genetics 36, 827-835. PMID: 15258583.
9. During, MJ, Cao, L, Zuzga, D, Francis, J, Fitzsimons, H, Jiao, X, Bland, B, Klugmann, M, Banks, W, Drucker, DJ, Haile, C. (2003) Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nature Medicine 9, 1173-1179. PMID: 12925848.
10. Cao, L, During, MJ, Xiao, W. (2002) Replication competent helper functions for recombinant AAV vector generation. Gene Therapy 9, 1199-1206. PMID: 12215886.
11. Cao, L, Liu, Y, During, MJ, Xiao, W. (2000) High titer, wild-type free rAAV vector production using intron-containing helper plasmids. Journal of Virology. 74, 11456-11463. PMID: 11090141.