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Jun-Li Liu, PhD Associate Professor, Department of Medicine 1001 Décarie Blvd. Room E02.7220 Tel: 514-934-1934 ext. 35059 jun-li.liu [at] mcgill.ca
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Biographical Sketch
Degrees and training
BSc. Peking University, China 1978-1982 Biology
MSc. Peking University, Health Science Centre, China 1982-1985 Physiology
PhD. McGill University, Montreal, Canada 1990-1995 Experimental Medicine
Postdoctoral fellow. National Institutes of Health, NIDDK, Bethesda, MD 1995-2000 Endocrinology
Positions and employment
2000-2008 Assistant Professor, Department of Medicine, McGill University, Montreal, Canada
2000- Medical Scientist, McGill University Health Centre, Montreal, Canada
2003- Member, Montreal Diabetes Research Centre, Montreal, Canada
2008- Associate Professor, Department of Medicine, McGill University, Montreal, Canada
2008- Editorial board, Journal of Diabetes, Blackwell Publishing
2017- Editorial board, Canadian Journal of Diabetes
Honors
1996-1999 Fellowship award, from Medical Research Council of Canada (at National Institutes of Health, Bethesda, MD).
1998 New Investigator Award, The Endocrine Society, Annual Meeting in New Orleans, LA.
1999 Fellows Award for Research Excellence, National Institutes of Health, Bethesda, MD
2000-2005 Career Development Award, Juvenile Diabetes Research Foundation International, NYC
2001 Travel Grant Award, The Endocrine Society, Annual Meeting in Denver, CO.
2005-2008 John R. & Clara M. Fraser Memorial Award, Faculty of Medicine, McGill University
2008-2011 Chercheurs boursiers Fondamental, Senior, Fonds de la recherché en santé Quebec
Keywords
Growth factors, cell replication, cell apoptosis, pancreatic islets, transgenic mice, gene regulation, insulin secretion, CCN5, WISP2, insulin-like growth factors, Reg proteins
Research or Clinical Activities
Insulin-like growth factor (IGF)-I is a peptide hormone mainly produced from the liver and other tissues at lower and variable levels. Research of last two decades by us and others has established that IGF-I is a potent growth factor for pancreatic islet cells, promotes cell survival and prevents onset of experimental diabetes. In order to explore where and how IGF-I acts on the islet cells, we have screened and identified the molecular targets using the technique of whole genome microarray. Prominently among the 82 preliminary targets we have discovered, CCN5/WISP2 has never been known to be expressed by the islet cells nor regulated by IGF-I. In a recent study we have shown that CCN5 is normally expressed in islet beta-cells, IGF-I directly stimulates its gene expression, and IGF-I overexpression caused increased level in the islets. We further demonstrate CCN5 overexpression accelerates the proliferation of insulinoma cells, activate signaling molecules Akt and/or Erk1/2 kinases, and CCN5 overexpression prevent cell death. We thus hypothesize that CCN5 is normally expressed by islet beta-cells and activated by IGF-I, its increased production promotes islet cell proliferation and regeneration, and survival, in concert to the action of IGF-I. We propose to establish a direct stimulation of CCN5 gene expression by IGF-I, the effects of in vitro administration of recombinant CCN5 on pancreatic islet cell proliferation and survival against harsh conditions, in vivo stimulation on pancreatic islet regeneration after removing part of the pancreas, and in vivo protection of CCN5 protein against experimental diabetes in mice. These studies will aid in the design of novel and potentially more effective therapeutic approaches exploiting CCN5 and its molecular targets, in improving the survival and function of the pancreatic islet cells.
On the other hand, we have (re)discovered the role of Reg proteins in diabetes, pancreatitis and pancreatic cancer. We study the role of Reg family proteins in pancreatic ductal adenocarcinoma (PDAC). Reg family proteins are normally expressed in the pancreas, some of which are known to promote cell proliferation and survival, are secreted and can be detected in serum. We discovered isoform- and cell-specific overexpression in ductal cancer cells, which might serve as specific markers for disease in diagnosis and treatment. The overexpression is also associated with acinar to ductal metaplasia (ADM), a possible cause of cancer origin. We hypothesize that increased expression of Reg proteins promote the development of ADM, PDAC or metastasis into extra pancreatic sites, thus can be targeted for cancer intervention, diagnosis or therapeutic monitoring. We propose (1) to screen for isoform-specific expression of Reg proteins in pancreatic cancer, (2) to correlate Reg protein expression with disease stage and other known markers, and (3) to study possible effect of Reg proteins in promoting ADM and cancer growth in cultured pancreatic cancer cells or in mutant laboratory mice.
Selected Recent Publications
Zhang H, Corredor ALG, Messina-Pacheco J, Li Q, Zogopoulos G, Kaddour N, Wang Y, Shi BY, Gregorieff A, Liu JL, Gao ZH. REG3A/REG3B promotes acinar to ductal metaplasia through binding to EXTL3 and activating the RAS-RAF-MEK-ERK signaling pathway. Commun Biol. 2021 Jun 7;4(1):688. doi: 10.1038/s42003-021-02193-z. PubMed PMID: 34099862; PubMed Central PMCID: PMC8184755.
Liu JL, Segovia I, Yuan XL, Gao ZH. Controversial Roles of Gut Microbiota-Derived Short-Chain Fatty Acids (SCFAs) on Pancreatic β-Cell Growth and Insulin Secretion. Int J Mol Sci. 2020 Jan 30;21(3). doi: 10.3390/ijms21030910. Review. PubMed PMID: 32019155; PubMed Central PMCID: PMC7037182.
Kaddour N, Zhang D, Gao ZH, Liu JL. Recombinant protein CCN5/WISP2 promotes islet cell proliferation and survival in vitro. Growth Factors. 2019 Aug;37(3-4):120-130. doi: 10.1080/08977194.2019.1652400. Epub 2019 Aug 22. PubMed PMID: 31437074.
Liu JL, Gao ZH. Does GLP-1 suppress hepatocyte glucose production directly, via fibroblast growth factor 21?. EBioMedicine. 2019 Mar;41:5-6. doi: 10.1016/j.ebiom.2019.03.012. Epub 2019 Mar 12. PubMed PMID: 30876763; PubMed Central PMCID: PMC6443942.
Li Q, Li B, Miao X, Ramgattie C, Gao ZH, Liu JL. Reg2 Expression Is Required for Pancreatic Islet Compensation in Response to Aging and High-Fat Diet-Induced Obesity. Endocrinology. 2017 Jun 1;158(6):1634-1644. doi: 10.1210/en.2016-1551. PubMed PMID: 28009527.