DEPARTMENT: Basic Sciences Research CAMPUS AFFILIATION: North OFFICE: Geisinger Commonwealth School of MedicineMedical Sciences Building525 Pine St., Office 2028Scranton, PA 18509 PHONE: 570-504-9644 FAX: 570-504-9618 EMAIL: firstname.lastname@example.org EDUCATION: BSc – Anhui Normal University, China PhD – Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, China Postdoctoral – University of California, Riverside, Calif. BIO: Jun Ling, PhD is associate professor of molecular biology in the Department of Basic Sciences. Dr. Ling holds a PhD in biochemistry and molecular biology from Shanghai Institute of Biochemistry and cell biology, Chinese Academy of Sciences. Dr. Ling completed a postdoctoral fellowship in University of California, Riverside. He was a research assistant professor in the biomedical division with UCR/UCLA Thomas Haider Biomedical Program. Dr. Ling was also a visiting scientist at the School of Medicine, Loma Linda University, California. His research interests are in the translational study on breast cancer development and therapies regulated by signal transduction and gene expression. EDUCATIONAL INTERESTS: Teaching courses of immunology, human genetics, cell biology and case-based learning (CBL) RESEARCH INTERESTS: Regulation of cancer development by signal transduction and mRNA translation RESEARCH DESCRIPTION: Studies in Dr. Ling’s lab focus on the investigation of molecular mechanisms of breast cancer initiation, progression and therapy, aiming to identify new targets for the development of new diagnostic and therapeutic strategies. The detailed research projects are conducted in following areas: Regulation of cancer development by mRNA translation mRNA translation is a fundamental process of gene expression that plays an indispensable role in human physiology and pathology. The malfunction of mRNA translation is closely involved in cancer initiation and progression. A number of translational initiation factors (eIF) function as proto-oncogene (e.g., eIF4E and eIF4G) or tumor suppressor (e.g., IF4E-binding protein/4E-BP). The focus in Ling lab is to investigate how eIFs are regulated by cell signaling that leads to the modulation of global and selective mRNA translation during cancer progression. Roles of PAK2 and PIM1 kinase in cancer development and therapy Signal transduction is a critical mechanism regulating most aspects of cancer development. Our research is concentrated on PAK2 kinase, a small G-protein activated kinase that can be stimulated by various stress conditions and cleaved by caspase 3 for constitutive activation. Another kinase in our study is PIM1 kinase, an oncogenic kinase with proliferative and pro-survival functions. By studying this “yin-yang” regulation through kinases, we expect to identify some new targets that can contribute to cancer diagnosis and treatment. Regulation of breast cancer development by functional interaction between NFkB and GR (glucocorticoid receptor) Chronic inflammation is one of key factors driving breast cancer progression and recurrence. NFkB and GR are two crucial transcription factors regulating inflammation, wherein NFkB is pro-inflammatory and GR is anti-inflammatory. While GR has been known to trans-repress NFkB activity for its anti-inflammatory activity, its specific effects on breast cancer have not been well studied, thus becoming one of our focused projects to study breast cancer development at gene transcriptional level. STUDENT RESEARCH OPPORTUNITIES: With the expertise and experience of Dr. Ling’s lab in molecular cancer biology, students can receive strict trainings in his lab on molecular biology, biochemistry and cell biology. They can participate in various projects of Ling lab or develop their own projects under the advice of Dr. Ling. Specifically students can work in following areas: 1) Gene manipulations, including gene cloning, mutation and expression. 2) Gene expression in bacterial, insect, mammalian and in vitro systems. 3) Protein engineering and purification for functional analysis. 4) RNA biochemistry, including in vitro transcription, RNAi, and mRNA translational assays. 5) Cell culture, transfection and cell-based assays. 6) Biophysical techniques (e.g. Surface plasmon resonance, SPR) for label-free binding analysis in biomarker diagnosis and drug development. PUBLICATIONS: J. Ling, C. Brey, M. Schilling, F. Lateef, Z. P. Lopez-Dee, K. Fernandes, K. Thiruchelvam, Yi Wang, K. Chandel, K. Rau, R. Parhar, F. Al-Mohanna, R. Gaugler, and S. Hashmi (2017). Defective lipid metabolism associated with mutation in klf-2 and klf-3: important roles of essential dietary salts in fat storage. Nutrition and Metabolism. 14:22 DOI 10.1186/s12986-017-0172-8. Jun Ling, Zenaida P. Lopez-Dee, Colby Cottell, Laura Wolfe, Derek Nye (2016) Regulation of mRNA Translation is a Novel Mechanism for Phthalate Toxicity. PLoS ONE. 11(12): e0167914. doi:10.1371/journal. pone.0167914. Ling J, Corneillie S, Cottell C, Traugh JA (2016) Activation of PAK2 by Serum Starvation Sensitizes its Response to Insulin Treatment in Adipocyte 3T3-L1 Cells. Biochem Anal Biochem 5: 277. doi:10.4172/2161-1009.1000277. Gutierrez LS, Ling J, Nye D, Papathomas K, Dickinson C. (2015) Thrombospondin peptide ABT-898 inhibits inflammation and angiogenesis in a colitis model. World J Gastroenterol . 21 (20):6157-6166. JinXiao Liang, Zhen Ning, Wei Gao, Jun Ling, A-Man Wang, HaiFeng Luo, Yong Liang, ZhongYu Wang and Qiu Yan (2014) Ubiquitin-specific protease 22-induced autophagy is correlated with poor prognosis of pancreatic cancer. Oncology Reports. 2014 Sep 22. doi: 10.3892/or.2014.3508. [Epub ahead of print] Khan SH, Lopez-dee Z, Kumar R and Ling J (2013) Activation of NFkB is a novel mechanism of pro-survival activity of glucocorticoids in breast cancer cells. Cancer Letters, 337(1):90-95 . Khan SH, Awasthi S, Guo C, Goswami D, Ling J, Griffin PR, Simons SS Jr, Kumar R (2012) Binding of the N-terminal Region of Coactivator TIF2 to the Intrinsically Disordered AF1 Domain of the Glucocorticoid Receptor Is Accompanied by Conformational Reorganizations. J Biol Chem. 287(53):44546-60. Jun Ling and Raj Kumar (2012) Crosstalk between NFkB and Glucocorticoid Signaling: a Potential Target of Breast Cancer Therapy. Cancer Letters. 322(2):119-26. David Lo, Jun Ling and Holly A Eckelhoefer (2012) M cell targeting by a Claudin 4 targeting peptide can enhance mucosal IgA response. BMC Biotechnology. 12:7 doi:10.1186/1472-6750-12-7 Shagufta H. Khan, Kriszta Farkas, Raj Kumar, and Jun Ling (2012) A versatile method to measure the binding to basic proteins by surface plasmon resonance. Analytical Biochemistry,421:385–390. Jun Ling (2011) Translation of the human genome (Editorial). Biochem. & Anal. Biochem. 1:1, doi: 10.4172/2161-1009.1000101e. Shagufta H. Khan, Jun Ling, and Raj Kumar (2011) Structure and functions of the N-terminal activation function (AF1) domain of the glucocorticoid receptor. PLoS ONE, 6(7): e21939. doi:10.1371/journal.pone.0021939 Jun Ling, Marina Zemskova, Kangling Zhang, Colby Cottell, Charles Karcutskie, Michael Lilly (2011) Phosphorylation of NFkB1/p105 by PIM1 kinase at a novel Ser937 site enhances its transcriptional activity and cancer cell proliferation. Proceedings of American Association of Cancer Research, Vol.52:1195. de Victoria AL, Gorham RD Jr, Bellows ML, Ling J, Lo DD, Floudas CA, Morikis D. (2011) A New Generation of Potent Complement Inhibitors of the Compstatin Family.Chem. Biol. Drug Design.77(6):431-40. Eckelhoefer, H.A., Rajapaksa, T.E., Wang, J., Stover-Hamer, M., Appleby, N.C., Ling, J., Lo, D.D. (2011). Claudin-4: Functional studies beyond the tight junction. In Claudins: Methods and protocols, Methods in Molecular Biology series. Vol. 762:115-128. Nye D, Lopez-Dee Z, Simone C, Papathomas K, Ling J, Gutierrez L (2009). “Thrombospondin 1 regulates interleukin 6 by an angiogenic mechanism mediated by TGFbeta1.” Inflammatory Bowel Diseases, Volume 15, Issue S2 (p S1-S65). Ling, J. Liao, H., Clark, R., Wang, M. and Lo, D. (2008) Structural Constraints for the binding of short peptides to claudin-4 revealed by surface plasmon resonance. J. Biol. Chem. 283(45):30585-95. Jun Ling, Simon J. Morley and Jolinda A. Traugh. (2005) Inhibition of cap-dependent translation via phosphorylation of eIF4G by protein kinase Pak2. EMBO J. 24(23):4094-4105 (highlighted paper). Orton KC, Ling J, Waskiewicz AJ, Cooper JA, Merrick WC, Korneeva NL, Rhoads RE, Sonenberg N, Traugh JA. (2004)Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits phosphorylation and interaction of eIF4G with Mnk. J. Biol. Chem. 279(37):38649-57. Miah SM, Sada K, Tuazon T, Ling J, Maeno K, Kyo S, Qu X, Tohyama Y, Traugh JA, Yamamura H. (2004) Activation of Syk protein tyrosine kinase in response to osmotic stress requires interaction with p21-activated protein kinase Pak2/gamma-PAK. Mol. Cell Biol. 24(1):71-83. Zhongdong Huang, Jun Ling, and Jolinda A. Traugh. (2003) Localization of p21-activated protein kinase g-PAK in the endoplasmic reticulum is required for induction of cytostasis. J. Biol. Chem. 278(15):13101-13109. Zhong Chen, Todd E. Young, Jun Ling, Su chich Chang and Daniel R. Gallie. (2003) Increasing vitamin C content of plants through enhanced ascorbate recycling. Proc. Natl.Acad. Sci. 100:3525-3530. Jun Ling, Simon J. Morley, Virgina M. Pain, William F. Marzluff and Daniel R. Gallie. (2002) The histone 3’-terminal stem-loop-binding protein enhances translation through a functional and physical interaction with eukaryotic initiation factor 4G (eIF-4G) and eIF-3. Mol. Cell Biol. 22:7853-7867. Young TE*, Ling J*, Geislerler-Lee CJ*, Tanguay RL, Caldwell C and Gallie DR. (2001) Developmental and thermal regulation of the maize heat shock protein, HSP101. Plant Physiol. 127(3):777-791. (* equal contribution) Ling, J., Wells, D.R., Tanguay, R.L., Dickey, L.F., Thompson, W.F., and Gallie, D.R. (2000) Heat shock protein HSP101 binds to the Fed-1 internal light regulatory element and mediates its high translational activity. The Plant Cell 12(7):1213-1228. Gallie, D.R., Ling, J., Niepel, M., Morley, S.J. and Pain, V.M. (2000) The role of 5’-leader, secondary structure and PABP concentration on cap and poly (A) tail function during translation in Xenopus oocytes. Nucleic Acids Res. 28(15): 2943-2953. Niepel, M., Ling, J. and Gallie, D.R. (1999) Secondary structure in the 5’-leader or 3’-untranslated region reduces protein yield but does not affect the functional interaction between the 5’-cap and the poly(A) tail. FEBS Lett. 462:79-84. Ling, J., Gao, X., Liu, W.Y. and Ruan, K.C. (1998) DNA-cleaving activity of superoxide dismutase specific for circular supercoiled double-stranded DNA in vitro. Int. J. Biochem. Cell Biol. 30(10):1123-1127. Ling, J. and Liu, W.Y. (1996) Cytotoxicity of two new ribosome-inactivating proteins, cinnamomin and camphorin, to carcinoma cells. Cell Biochem and Function. 14:157-161. Ling, J. Li, X.D., Wu, X.H. and Liu, W.Y. (1995) Topological requirement for recognition and cleavage of DNA by ribosome-inactivating protein. Biol. Chem. 376:637-641. Ling, J., Liu, W.Y. and Wang, T.P. (1995) Simultaneous existence of two types of ribosome-inactivating proteins in the seed of Cinnamomum camphora—–RNA N-glycosidase activity of these cytotoxic proteins. Biochim. Biophys. Acta. 1252:15-22. Li, Q., Ling, J. and Liu, W.Y. (1995) Partial restoration of inactivated ribosome with sodium borohydride or amino acids. FEBS Lett. 370:123-126. Gao, W., Ling, J., Zhong, X and Zhang, Z. (1994) Luffin-S: a small novel ribosome-inactivating protein from Luffa cylindrica: characterization and mechanism studies. FEBS Lett. 347:257-260. Ling, J., Liu, W.Y. and Wang, T.P. (1994) Radioassay for RNA N-glycosidase activity with tritium-labeled sodium borohydride. Bioorganic Chem. 22:295-304. Ling, J., Liu, W.Y. and Wang, T.P. (1994) Cleavage of supercoiled double stranded DNA by several ribosome-inactivating proteins in vitro. FEBS Lett. 23:143-146.