I received my first postgraduate degree at the Beijing Institute for Cancer Research (Peking University) studying the relationship of oncogenic activity (i.e., c-myc and c-ras) and tumour metastasis. This was when I first became fascinated with genes. Following my Master's study I went to the Biology Department at the University of Saskatchewan and obtained my Ph.D. degree in Genetics with Gerry Rank. My current research interests began with my Postdoctoral work in Vikram Misra's laboratory at the Western College of Veterinary Medicine. At that time people were very intrigued by a cellular protein, Host Cell Factor C1 (HCF or HCF1) which is required by the human herpes virus-1 protein VP16 to initiate the viral gene expression cascade during lytic infection. Among several groups competing to identify cellular ligands for HCF1, I was the first to discover two novel human proteins that interact with HCF1, namely Luman (also called LZIP) and Zhangfei. Most interestingly, we and others have found out that the viral protein VP16 mimics the mode of interaction of Luman/Zhangfei with HCF1. This discovery has led to the hypothesis that Luman/Zhangfei-mediated cell signaling pathways are targeted by the viral mimicry and may be critical for the herpes virus infection cycle. Later, I did a short Postdoc with Tom Kristie at NIH investigating the cellular role of HCF1. In 2001 I took a faculty position here at the University of Guelph and have continued to work on the biological function of Luman and Zhangfei.
I. Unfolded Protein Response and Human Diseases
During the course of our study of gene regulation events in virus-host cell interaction, we have identified three new cellular proteins, Luman/CREB3, Zhangfei/CREBZF, and Luman-recruiting factor (LRF). These proteins play key roles in animal stress responses, specifically the Unfolded Protein Response (UPR) that is caused by stress in the endoplasmic reticulum. The UPR has been linked to animal development, cell differentiation, as well as a variety of human diseases such as Alzheimer’s, diabetes, cancer and viral infection. We are currently using gene knockout mouse models, combined with molecular and cellular biology techniques to study -
- Stress signaling mediated by these proteins (their upstream and downstream targets), and how it is related to cellular processes or animal diseases (lipid metabolism/obesity, hypoxia/cancer, glucose metabolism/diabetes, and inflammation);
- The molecular mechanism of how these genes/proteins are regulated during the stress response (e.g., transcriptional regulation, protein translational modification and trafficking etc).
II. Molecular Mechanisms of Aging
Another new and exciting field that we have recently undertaken is to study of the mechanisms of aging using planarians (flat worms). The planarians are potentially a better model system than traditional fruitflies and C. elegans (round worms), both of which have undergone extensive gene loss during evolution and are largely post-mitotic in their adult life. We are working to establish planarians as a new aging model to test the hypothesis that longevity requires multiplex resistance to stress. We hope to identify genes or alleles that confer such multiplex stress resistance and/or promote longevity.
Keywords: cell signaling, animal stress response, unfolded protein response, gene-knockout mouse, virus-cell interaction, aging mechanism, planarians
Denboer LM, A Iyer, AR McCluggage, Y Li, AD Martyn and R Lu. (2013) JAB1/CSN5 inhibits the activity of Luman/CREB3 by promoting its degradation. BBA - Gene Regulatory Mechanisms 1829, 921-929.
Martyn, AC, E Choleris, DJ Gillis, JN Armstrong, TR Amor, ARR McCluggage, PV Turner, G Liang, K Cai and R Lu (2012). Luman/CREB3 recruitment factor (LRF) regulates glucocorticoid receptor activity and is essential for prolactin-mediated maternal instinct. Molecular and Cellular Biology DOI 10.1128/MCB.01142-12.
Burnett, HF, TE Audas, G Liang and R Lu (2012) Herpes simplex virus-1 disarms the unfolded protein response in the early stages of infection.Cell Stress and Chaperones. DOI 10.1007/s12192-012-0324-8.
Lu, R. (2011) CREB3. Nature Molecular Pages. http://www.signaling-gateway.org/molecule/query?afcsid=A003216. (Invited review).
Mitchell, GB, ME Clark, R Lu, and JL Caswell (2010) Localization and Functional Characterization of Pulmonary Bovine Odorant-Binding Protein. Veterinary Pathology, DOI: 10.1177/0300985810381907.
Song, C, R. Lu, D. Bienzle, H-C Liu, and D Yoo. (2009) Interaction of porcine reproductive and respiratory syndrome virus nucleocapsid protein with the inhibitor of MyoD family-a domain-containing protein.Biological Chemistry 390, 215–223.
Audas, TE, Y Li, G Liang and R Lu. (2008) A novel protein, Luman recruitment factor (LRF), inhibits Luman activation of the unfolded protein response.Molecular and Cellular Biology, 12, 3952-3966.
Liang, G, TE Audas, Y Li, GP Cockram, JD Dean, AC Martyn, K Kokame, and R Lu. (2006) Luman/CREB3 induces transcription of the endoplasmic reticulum stress response protein, Herp, through an ERSE-II element.Molecular and Cellular Biology 26, 7999-8010.
Hogan, MR, GP Cockram, and R Lu. (2006). Cooperative interaction of Zhangfei and ATF4 in transactivation of the cyclic AMP response element.FEBS Letters 580, 58-62.
Lu, R and V Misra. (2000) Zhangfei: a second cellular protein interacts with herpes simplex virus accessory factor HCF in a manner similar to Luman and VP16. Nucleic Acids Research 28, 2446-2454.
Lu, R and V Misra (2000) Potential role for Luman, the cellular homologue of herpes simplex virus VP16 (alpha gene trans-inducing factor), in herpesvirus latency. Journal of Virology 74, 934-943.
Lu, R, P Yang, S Padmakumar and V Misra. (1998) The herpesvirus transactivator VP16 mimics a human bZIP protein, Luman, in its interaction with HCF. Journal of Virology 72, 6291-6297.
Lu, R., P Yang, P O'Hare and V Misra. (1997) Luman, a new member of the CREB/ATF family, binds to herpes simplex virus VP16-associated host cellular factor. Molecular and Cellular Biology 17, 5117-5126.
MCB*2050 Molecular Biology of the Cell
MCB*6310 Advanced Topics in Developmental & Cellular Biology
Graduate student positions are available.