Dr. Ray Lu

I received my first postgraduate degree at the Beijing Institute for Cancer Research (Peking University) studying the relationship between oncogenes (e.g., c-myc and c-ras) and tumour metastasis. This was when I first became fascinated about genes and gene regulations. Following my Master's study I went to the Biology Department at the University of Saskatchewan and obtained my Ph.D. degree in Molecular Genetics with Gerry Rank. My current research interests began with my postdoctoral work in Vikram Misra's lab 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) that is required by the human herpes virus-1 protein VP16 to initiate the viral gene expression cascade during lytic infection. Among several groups racing to identify cellular ligands for HCF1, I was the first to discover two novel human genes that interact with HCF1, namely Luman (also called LZIP in mice, official Genbank name CREB3) and Zhangfei (or CREBZF). Most interestingly, we and others have found out that the viral protein VP16 mimics the mode of interactions of Luman/Zhangfei with HCF1. This discovery has led to the hypothesis that Luman/Zhangfei mediates certain cell stress signaling that is targeted by the viral mimicry critical for the herpes virus infection cycle. This theory holds true to date with accumulating supportive experimental evidence. Later, I did a short postdoc with Tom Kristie at the National Institute of Allergy and Infectious Diseases (NIAID) in 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/CREB3, Zhangfei/CREBZF and LRF/CREBRF (later discovered in Guelph), and their related stress responses.

• BSc, Wuhan University
• MSc, Beijing University
• PhD, University of Saskatchewan

Key words: ER and Golgi stress; Unfolded Protein Response (UPR); glucocorticoid signaling; gene knockout mice; animal stress; metabolism

During the course of our study of gene regulatary events in virus-host cell interactions, we have identified three new cellular proteins, Luman/CREB3, Zhangfei/CREBZF, and Luman-recruiting factor LRF (or CREBRF). We and others have since produced strong evidence suggesting that these proteins play key roles in cellular stress responses, specifically the Unfolded Protein Response (UPR) triggered primarily by disruption of homeostasis in the endoplasmic reticulum and the Golgi. 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.

In recent years our research has expanded from molecular genetics and cell biology to animal physiology and neuroscience. We have established CREB3- and CREBRF-gene knockout mouse models, both of which showed strikingly similar phenotype – lean and blunted stress response. We have since discovered that CREB3 and CREBRF are regulators of the glucocorticoid signaling and key modulators of lipid metabolism. Our ongoing research falls into the following themes –

1) How CREB3 and CREBRF mediate stress signaling, what their upstream and downstream targets are, and how this is related to cellular processes and animal diseases, such as metabolic disorders such as obesity/diabetes and animal stress-related disorders including animal welfare.

2) What are the genetic variations responsible for the differences among individuals in the response to stresses or susceptibility to metabolic disorders?

• Smith, B.S., Hewitt, T., Bakovic, M. & Lu, R. (2023). ER stress-associated transcription facto CREB3 is essential for normal Ca2+, ATP, and ROS homeostasis. Mitochondrian. https://doi.org/10.1016/j.mito.2023.01.001
• Smith BS, KH. Diaguarachchige De Silva, A Hashemi, RE Duncan, S Grapentine, M Bakovic, and R Lu (2022). Transcription factor CREB3 is a potent regulator of high-fat diet-induced obesity and energy metabolism. International Journal of Obesity (Nature). doi.org/10.1038/s41366-022-01128-w.
• Larson, S., R Zhou, K Lu, Y Zhang, M Jafarikia, R Bergeron and R Lu (2021). Genetic diversity at the stress regulatory gene Luman/CREB3 of Yorkshire and Meishan pigs. Canadian Journal of Animal Science., doi:10.1139/CJAS-2020-0155.
• Larson, S., A Arrazola, K Morrissey, R Parra, T Faulkner, M Jafarikia, I Mandell, R Bergeron and R Lu (2021). Genetic variation in Luman/CREB3 and association with stress and meat quality traits in Yorkshire pigs. Canadian Journal of Animal Science., doi: 10.1139/CJAS-2020-0156.
• Frahm K, A Williams, A Wood, M Ewing, P Mattila, B Chuan, L Guo, F Shah, C O'Donnell, R Lu and DB DeFranco (2020). Loss of CREBRF Reduces Anxiety-like Behaviors and Circulating Glucocorticoids in Male and Female Mice. Endocrinology. 161(11). DOI:10.1210/endocr/bqaa163
• Penney J, T Taylor, N MacLusky and R Lu. (2018). LUMAN/CREB3 Plays a Dual Role in Stress Responses as a Cofactor of the Glucocorticoid Receptor and a Regulator of Secretion. Frontiers in Molecular Neuroscience, 11, 352 – 362.
• Penney J, A Mendell, M Zeng, K Tran, J Lymer, PV Turner, E Choleris, N MacLusky and R Lu (2017). LUMAN/CREB3 is a key regulator of glucocorticoid-mediated stress responses. Molecular and Cellular Endocrinology, 439, 95104, doi: 10.1016/j.mce.2016.10.022.
• Yankulov K and R Lu (2017). On the Possibility of Preferred Performance Styles and Their Link to Learning Styles. Frontiers in Education, doi: 10.3389/feduc.2017.00032.
• Audas, TE, PW Hardy-Smith, J Penney, T Taylor and R Lu (2016). Characterization of nuclear foci-targeting of Luman/CREB3 recruitment factor (LRF/CREBRF) and its potential role in inhibition of herpes simplex virus-1 replication. European Journal of Cell Biology, 611-622 (12), 611-622, doi: 10.1016/j.ejcb.2016.10.006.
• Hufnagel, D, S Chang, J Zhang and R Lu (2015). Analysis of Methanogen Communities in Anaerobic Membrane Bioreactors and Conventional Anaerobic Digester Systems. Journal of Advances in Biology & Biotechnology, 4(2), 1-9, doi: 10.9734/JABB/2015/18655.
• Tatiersky, L., Rollins-Smith, A Louise, R Lu, C Jardine, IK Barker, ME Clark and JL Caswell (2015). Effect of glucocorticoids on expression of cutaneous antimicrobial peptides in northern leopard frogs (Lithobates pipiens). BMC Veterinary Research, doi: 10.1186/s12917-015-0506-6.
• Choleris, E., L Cazzin, JM Lymer, TR Amor, and R Lu (2013). Acute corticosterone sexually dimorphically facilitates social learning and inhibits feeding in mice. Neuropsychopharmacology. 75:191-200. doi: 10.1016/j.neuropharm.2013.07.011.
• 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.

• BIOL*1090 Introduction to Molecular and Cellular Biology (current)
• MCB*2050 Molecular Biology of the Cell
• MBG*3040 Molecular Biology of the Gene
• MBG*4240 Applied Molecular Genetics in Medicine and Biotechnology (current)
• MICR*4330 Molecular Virology

Graduate Students

• Kaitlyn Blundon
• Brian Chiu
• Marina Figueira
• Hailey Larkin

Opportunities

Graduate student positions are available.