Hang Yin

Hang Hubert YIN

Associate Professor

Office: JSCBB A224
Lab: JSCBB A250/260/270/280
Office Phone:  303 492 6786
Lab Phone:  303 492 8607
Lab Website: Yin Group
Email: hubert.yin at colorado.edu

 
  • Ph.D.: Yale University (2004)
  • Postdoc: University of Pennsylvania School of Medicine (2004 - 2007)

 

Awards

  • CAPA Distinguished Junior Faculty Award (2012)
  • SU2C IRG Award (2010)
  • NSF CAREER Award (2010)
  • AACR Gertrude B. Elion Cancer Research Award (2009)
  • University of Colorado New Inventor of the Year (2009)
  • NIDA ECHEM Award (2009)
  • NIDA CEBRA Award (2009)
  • Sidney Kimmel Scholars Award (2008)
  • HHMI Collaborative Innovation Award (2008)
  • CRCW Junior Faculty Development Award (2008)
  • IUBMB Wood-Whelan Research Fellowship (2007)
  • ADDF Young Investigator Scholarship (2007)
  • Elsevier Most Cited Paper 2004-2007 Award (2007)

 

Affiliations

 

Research Overview

  • Drug Discovery: Potential Therapeutics that Inhibit Toll-like Receptors. Pain remains a significant public health issue with two-thirds of patients achieving little to no pain relief from the myriad of currently available pharmacotherapies and dosing regimens. The use of opioid (e.g. morphine) pharmacotherapies produces several rewarding and reinforcing side effects, which result in the drugs’ diversion to abuse settings. Glial cells have been found to play a critical role in initiating and maintaining increased nociception in response to peripheral nerve injury. The opioids-induced glial cell activation attenuates opioid-induced pain suppression and enhances the development of opioid tolerance and dependence, the drug reward, and other negative side effects such as respiratory depression. We are interested in employing structure-based drug design and high-throughput screening techniques to identify novel small-molecule inhibitors of TLR4 that regulates glial cell activation. The identified agents will potentially serve as therapeutics that suppresses opioid-dependence and tolerance. Using this method, we also successfully identified small molecule inhibitors that disrupt the TLR3-dsRNA interactions. This is significant because the protein-RNA complex is a challenging target for small molecule probes. Our goal is to develop a generally applicable method to provide small molecule probes for the protein-protein and protein-RNA interactions of these clinically relevant TLRs.

 

  • Protein Engineering: Peptides Targeting Transmembrane Domains of Proteins. Protein transmembrane domains (TMDs) regulate many pivotal biological processes, including cell signal transduction, cancer development, ion transmission, and membrane protein folding. However, the molecular recognition in membranes is little understood due to the lack of available probes with high affinity and specificity. Conventional tools such as antibodies are unable to bind to the transmembrane regions of membrane proteins. A second project in our lab is to develop exogenous peptide and small-molecule agents that target transmembrane helices. Using these agents, we can study these important membrane protein-protein interactions, thereby further our understanding of molecular recognition in membranes. As a proof-of-principle, we developed novel peptide/peptidomimetic reagents to recognize the TMDs of latent membrane proteins 1 (LMP-1) found in the human Epstein-Barr herpesvirus lymphomas and syndromes. These designed peptides will be used to study TMD-mediated LMP-1 activation. The findings from these studies will lay the groundwork for the discovery of new pharmaceutical agents with which we can prevent, diagnose, and treat herpesvirus-dependent cancers.

 

  • Biotechnology Development: Non-invasive Cancer Biomarkers. Elevated microvesicle (MV) shedding is an indication of cancer metastasis. Sensing their highly curved membrane may provide a novel strategy to detect these MVs, which renders potentials of developing diagnostic, prognostic, and therapeutic agents. We employed a multidisciplinary approach, utilizing our expertise in computational modeling, membrane biophysics, and cellular assay development to rationally design novel tools that sense and regulate membrane curvature and lipid components. These rationally designed agents not only help us to understand the critical protein-lipid interactions but also provide prototypes that may eventually lead to novel cancer biomarkers.

 

Selected Publications (PubMed search for a full publication list)

  • Exosomes and Microvesicles: Identification and Targeting by Particle Size and Lipid Chemical Probes (2014), Kastelowtiz, N; Yin, H; ChemBioChem 15, in press.
  • The Development of Antimicrobial Alpha-AApeptides that Suppress Pro-Inflammatory Immune Responses (2014), Shruti, P; Smith, C; Wu, H; Li, Y; Manoj, N; Qiao, Q; Zoya, H; Cao, C; Yin, H; Cai, J; ChemBioChem 15, 688-694.
  • Lipidated Cyclic Gamma-AApeptides Display Both Antimicrobial and Anti-Inflammatory Activity (2014), Li, Y; Smith, C; Wu, H; Padhee, S; Manoj, N; Cardiello, J; Qiao, Q; Cao, C; Yin, H; Cai, J; ACS Chem. Biol. 8, 211-217.
  • Changes in Lipid Density Induce Membrane Curvature (2013), de Jesus, AJ; Kastelowtiz, N; Yin, H; RSC Adv. 3, 13622-13625
  • Rifampin Inhibits Toll-Like Receptor 4 Signaling by Targeting Myeloid Differentiation Protein 2 and Attenuates Neuropathic Pain (2013), Wang, XH; Grace, PM; Pham, MN; Cheng, K; Strand, KA; Smith, C; Li, J; Watkins, LR; Yin, H; FASEB J. 272713-2722.
  • Targeting Toll-Like Receptors with Small Molecule Agents (2013), Wang, XH; Smith, C; Yin, H; Chem. Soc. Rev. 42, 4859-4866 (cover article). 
  • Multivalency Amplifies the Selection and Affinity of Bradykinin-Derived Peptide for Lipid Nanovesicles (2013), Saludes, JP; Morton, LA; Coulup, SK; Fiorini, Z; Cook, BM; Beninson, L; Chapman, ER; Fleshner, M; Yin, H; Mol. Biosyst. 9, 2005-2009 (cover article). 
  • PNA-Based MicroRNA Inhibitors Elicit Anti-Inflammatory Effects in Microglia Cells (2013),  Brown, PN; Yin, H; Chem. Commun. 49, 4415-4417 (Emerging Investigators special issue).
  • Toll-Like Receptors as Therapeutic Targets of Autoimmune Connective Tissue Diseases (2013), Li, J; Wang, XH; Zhang, FC; Yin, H; Pharmacol. & Ther. 138, 441-451.
  • MARCKS-ED Peptide as a Membrane Curvature Sensor (2013), Morton, LA; Saludes, JP; Fiorini, Z; Beninson, L; Chapman, ER; Fleshner, M; Yin, H; ACS Chem. Biol.8, 218-225. 
  • Computationally Designed Peptide Inhibitors Against the Ubiquitin E3 Ligase SCFFbx4 (2013), Lee, J; Sammond, DW; Fiorini, Z; Saludes, JP; Resch, MG; Hao, B; Wang, W; Yin, H;  Liu, X; ChemBioChem 14, 445-451.
  • Protein Engineering Methods Applied to Membrane Protein Targets (2013), Lluis, MW; Godfrody, JI; Yin, H; Protein Eng. Des. Select. 26, 91-100.
  • Discovery of Small-Molecules that Inhibit the Protein Complex of Toll-Like Receptor 1 and 2 (2012)Cheng, K; Wang, XH; Zhang, S; Yin, H; Angew. Chem. Int. Ed. 51, 12246-12249 (cover article; featured in “Science & Technology ConcentratesC&EN 2012, 90(35), 33). 
  • Isolated Toll-Like Receptor Transmembrane Domains are Capable of Oligomerization  (2012), Godfroy, JI; Roostan, M; Moroz, YS; Korendovych, IV; Yin, H; PLoS One 7, e48875.
  • Detection of Highly Curved Membrane Surfaces Using a Cyclic Peptide Derived from Synaptotagmin-I (2012), Saludes, JP; Morton, LA; Ghosh, N; Beninson, L; Chapman, ER; Fleshner, M; Yin, H; ACS Chem. Biol. 7, 1629-1635.
  • Repositioning Antimicrobial Agent Pentamidine as a Disruptor of the Lateral Interactions of Transmembrane Domain 5 of EBV Latent Membrane Protein 1 (2012), Wang, XH; Fiorini, Z; Smith, C; Li, J; Watkins, LR; Yin, H; PLoS One 7, e47703.
  • Selection, Synthesis, and Anti-Inflammatory Evaluation of the Arylidene Malonate Derivatives as TLR4 Signaling Inhibitor (2012), Zhang, ST; Cheng, K; Wang, XH; Yin, H; Bioorg. Med. Chem. 20, 6073-6079 (cover article).
  • Morphine Activates Neuroinflammation in a Parallel Manner to Endotoxin (2012), Wang, XH; Loram, LC; Ramos, K; de Jesus, A; Thomas, J; Cheng, K; Reddy, A; Somogyi, AA; Hutchinson, MR; Watkins, LR; Yin, H; Proc. Natl. Acad. Sci. U. S. A. 109, 6325-6330 (Research Highlights in Nature 2012, 484, 419).
  • Targeting the Lateral Interactions of Transmembrane Domain 5 of Epstein-Barr Virus Latent Membrane Protein 1 (2012), Wang, XH; Saludes, JP; Zhao, TX; Csakai, A; Fiorini, Z; Chavez, SA; Li, J; Lee, GI; Varga, K; Yin, H; Biochim. Biophys. Acta. 1818, 2282-2289.
  • Multi-Tox: A ToxR-Based Assay for Multi-Pass Transmembrane Domain Oligomerization (2011), Joce, C; Wiener, AA; Yin, H; Biochim. Biophys. Acta. 1808, 2948-2953.
  • Development of Beta-Amino Alcohol Derivatives that Inhibit Toll-Like Receptor 4 Mediated Inflammatory Resonse as Potential Antiseptics (2011), Chavez, SA; Martinko, AJ; Lau, C; Pham, MN; Cheng, K; Mollnes, TE; Yin, H; J. Med. Chem. 54, 4659-4669.
  • Transmembrane Peptides Used to Investigate the Homo-Oligomeric Interface and Binding Hot-Spot of Latent Membrane Protein 1 (2011), Sammond, DW; Joce, C; Takeshita, R; McQuate, S; Ghosh, N; Martin, JM; Yin, H; Biopolymers 95, 772-784 (cover article).
  • An MD2 Hot-Spot Mimicking Peptide that Suppresses TLR4-Mediated Inflammatory Respnose In Vitro an In Vivo (2011), Liu, L; Ghosh, N; Slivka, PF; Fiorini, Z; Hutchinson, MR; Watkins, LR; Yin, H; ChemBioChem 12, 1827-1831 (cover article).
  • Small Molecule Inhibitors of the TLR3/dsRNA Complex (2011), Cheng, K; Wang, XH; Yin, H; J. Am. Chem. Soc. 133, 3764-3767.
  • Application of a Novel In Silico High Throughput Screen to Identify Selective Inhibitors for Protein-Protein Interactions (2010), Joce, C; Stahl, JA; Shridhar, M; Hutchinson, MR; Watkins, LR; Fedichev, PO; Yin, H; Bioorg. Med. Chem. Lett. 20, 5411-5413.
  • Selection, Preparation, and Evaluation of Small-Molecule Inhibitors of Toll-Like Receptor 4 (2010), Bevan, DE; Martinko, AJ; Loram, LC; Stahl, JA; Taylor, FR; Joshee, S; Watkins, LR; Yin, H; ACS Med. Chem. Lett. 1, 194-198.
  • Toll-like Receptor 4 in CNS Pathologies (2010), Buchanan, MM; Hutchinson, MR; Watkins, LR; Yin, H; J. Neurochem. 114, 13-27.
  • Development of Agents That Modulate Protein-Protein Interactions in Membranes (2010), Zhao, TX; Martinko, AJ; Le, VH; Zhao, J; Yin, H;Curr. Pharm. Des16,1055-1062.
  • A Peptide Antagonist of the TLR4/MD2 Interaction (2009),Slivka, PF; Shridhar, M; Lee, GI; Sammond, DW; Hutchinson, MR; Martinko, AJ; Buchanan, MM; Sholar, PW; Kearney, JJ; Harrison, JA; Watkins, LR; Yin, H; ChemBioChem 10, 645-649.
  • Two Fluorescent Probes to Dissect the Binding, Insertion, and Dimerization Kinetics of a Model Membrane Peptide (2009), Tang, J; Yin, H; Qiu, J; Tucker, M; DeGrado, WF; Gai, F; J. Am. Chem. Soc. 131, 3816-3817.
  • Design, Synthesis, and Evaluation of Biotinylated Opioid Derivatives as Novel Probes to Study Opioid Pharmacology (2008), Li, Y; Chase, AR; Slivka, PF; Baggett, CT; Zhao, TX;Yin, H; Bioconjug. Chem19, 2585-2589.
  • Computationally Designed Peptide Inhibitors of Protein-Protein Interactions in Membranes (2008), Caputo, GA; Litvinov, RI; Li, W; Bennett, JS; DeGrado, WF; Yin, H; Biochemistry 47, 8600-8606.
  • Peptide Probes for Protein Transmembrane Domains (2008), Slivka, PF; Wong, J;Caputo, GA;Yin, H; ACS Chem. Biol. 3, 402-411.
  • Exogenous Agents that Target Transmembrane Domains of Proteins (2008), Yin, H; Angew. Chem. Int. Ed47, 2744-2752 (cover article).
  • Computational Design of Peptides that Target Transmembrane Helices (2007), Yin, H; Slusky, JS; Berger, BW; Walters, RS; Vilaire, G; Litvinov, RI; Lear, JD; Caputo, GA; Bennett, JS; DeGrado, WF; Science 315, 1817-1822.