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Pen-Jen Lin, PhD


Assistant Professor

Graduate College of Biomedical Sciences

E-Mail: plin@westernu.edu

Phone: 909-469-8696 |

Education

Ph.D. in Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 1999-2003

M.S. in Bio-Pharmaceutical Science, National Yang-Ming University, Taipei, Taiwan, 1995-1997

B.S. in Life Science, National Tsing-Hua University, Hsin-Chu, Taiwan, 1991-1995

Courses

Molecular and Cellular Basis of Medicine (Biochemistry)

GCBS 6101  Advanced Topics in Immunology

Research Interest

Endoplasmic reticulum -associated Degradation (ERAD) of misfolded proinsulin.

Since accumulation of misfolded proinsulin in the ER causes pancreatic β cells failure and results in permanent neonatal diabetes, understanding how misfolded proinsulin is recognized and retro-translocated from the Endoplasmic Reticulum (ER) lumen to the cytosol for degradation is an important biomedical issue.

We are currently spectroscopically monitoring the movement of misfolded proinsulins from the lumen of reconstituted ER microsomes to the cytosol.  Because these reconstituted ER microsomes contain only individual or a specific combination of lumenal chaperones, this approach will allow us to systematically assess the functional involvement of specific lumenal chaperones in recognizing and retro-translocating misfolded proinsulin for degradation.

 

Chaperone-assisted co-translational protein folding in the ER:

We have developed a novel system to spectroscopically monitor secretory protein (prolactin) co-translational folding in the ER and characterize the functional involvement of lumenal chaperones in the folding process.  We will characterize the extent of FRET-detected folding as a function of both nascent chain length and also lumenal content (using reconstituted ER microsomes) to determine which lumenal proteins and small molecules affect nascent chain folding, in what order, and whether they act singly or in concert with others.

Publication

Publications related to membrane protein folding and integration:

Hou, B., Lin, PJ, Johnson, A.E. (2012) "Membrane protein TM segments are retained at the translocon during integration until the nascent chain cues FRET-detected release into bulk lipid," Molecular Cell, 48: 398-408

Wu, C., Wei, J., Lin, P.J., Tu, L., Deutsch, C, Johnson, A.E. and Sachs M.S. (2012) “Arginine-dependent Changes in Configuration of the Arginine Attenuator Peptide in the Ribosome Tunnel,” Journal of Molecular Biology, 416: 518-533.

Lin, P.J., Jongsma, C.G., Pool, M.R. and Johnson, A.E. (2011) “Polytopic Membrane Protein Folding at L17 in the Ribosome Tunnel Initiates Cyclical Changes at the Translocon,” Journal of Cell Biology, 195, 55-70.

Lin, P.J., Jongsma, C.G., Liao, S. and Johnson, A.E. (2011) “Transmembrane Segments of Nascent Polytopic Membrane Proteins Control Cytosol/ER Targeting during Membrane Integration,” Journal of Cell Biology, 195, 41-54.

Publications related to the enzymes involved in the Vitamin K cycle:

Higgins-Gruber, S.L., Mutucumarana, V.P., Lin, P.J., Jorgenson, J.W., Stafford, D.W. and Straight, DL (2010). “Effect of Vitamin K-dependent Protein Precursor Propeptide, Vitamin K Hydroquinone, and Glutamate Substrate Binding on the Structure and Function of γ-Glutamyl Carboxylase,” Journal of Biological Chemistry, 285:31502-8.

Lin, P.J., Straight, D.L. and Stafford, D.W. (2004). “Binding of the Factor IX γ-Carboxyglutamic Acid Domain to the Vitamin K-dependent γ-Glutamyl Carboxylase Active Site Induces an Allosteric Effect That May Ensure Processive Carboxylation and Regulate the Release of Carboxylated Product,” Journal of Biological Chemistry, 279:6560-6566

Li, T., Chang, C.Y., Jin, D.Y., Lin, P.J., Khvorova, K. and Stafford, D.W. (2004). “Identification of the Gene for Vitamin K Epoxide Reductase,” Nature, 427: 541-544

Soute, B.A.M., Jin, D.Y., Spronk, H.M.H., Mutucumarana. V.P., Lin, P.J., Hackeng, T.M., Stafford, D.W. and Vermeer, C. (2004). “Characteristics of Recombinant W501S Mutated Human γ-Glutamyl Carboxylase,” Journal of Thrombosis and Haemostasis, 2 , 597-604

Wang, C.P., Yagi, K., Lin, P.J., Jin, D.Y., Makabe, K.W. and Stafford, D.W. (2003). “Identification of a Gene Encoding a Typical γ-Carboxyl-glutamic Acid Domain in the Tunicate Halocynthia Roretzi,” Journal of Thrombosis and Haemostasis, 1, 118-123

Lin, P.J., Jin, D.Y., Tie, J.K., Presnell, S.R., Straight, D.L. and Stafford, D.W. (2002). “The Putative Vitamin K-dependent γ-Glutamyl Carboxylase Internal Propeptide Appears to Be the Propeptide Binding Site,” Journal of Biological Chemistry, 277:28584-91

Stanley, T.B., Jin, D.Y., Lin, PJ. and Stafford, D.W. (1999). “The Propeptides of the Vitamin K-dependent Proteins Possess Different Affinities for the Vitamin K-dependent Carboxylase,” Journal of Biological Chemistry, 274:16940-4.