Ming Hansen-Gong

Ming Hansen-Gong taylorgong3616@gmail.com

(626) 759-2211212 E. 12TH St.

Imperial, NE 69033

Summary

Detail-oriented Analytical Chemist with expertise in design and develop analytical methods, as well as analyzing data and providing results. Experienced in instrument monitoring, troubleshooting and maintenance. An excellent team player and fast learner.

Experience

California State University, Los Angeles Graduate Assistant, 2012 - 2014

· Conducted experiments on Surface Plasmon Resonance, Atomic Absorption Spectrometer, Florescence, Atomic Force Microscopy, High Performance Liquid Chromatography, Mass Spectrometer, UV-visible, pH meter, Inductively Coupled Plasma Mass Spectrometry, Gas Chromatography· Supplied students with extra knowledge about subjects being studied· In charge of making presentation videos and writing lab manuals· Graded homework and lab reports

California State University, Los Angeles Research Professional, 2011 – 2014

· Conduct research projects on daily basis using various instruments· Planned and organized lab tours for visiting scholars· In charge of creating and filing paperwork· Organized lab meetings· Trained new students on lab instruments and procedures·Maintained lab instruments

Chase County Schools Para-professional English Language Learners, 2014 - 2015 · Help students understand curriculum through tutoring and scaffolding. All subject areas from kindergarten to 12th grade are gone over in a needs-based manner. Education Masters of Science in Chemistry, California State University, Los Angeles, 2014 http://www.calstatela.edu/ Bachelors of Science in Chemistry Liaoning Shihua University, 2010 http://www.lnpu.edu.cn/english/general/index.htm

Dr. Zhou Recommendation:

Dr. Zhou was my Personal Instructor from fall of 2011 to summer 2014 at California

State University, Los Angeles. He informed me to let hiring companies contact him in

regards to my recommendation.

Dr. Feimeng Zhou Professor of Chemical and Biochemical Department California State University, Los Angeles (323) 343-2300fzhou@exchange.calstatela.edu

Kinetic Studies of Amyloidogenic Hexapeptides as β-Amyloid (Aβ) Peptide Inhibitors

Graduate Prospectus by

Ming Gong

Abstract Aggregation of β-amyloid (Aβ) peptides has been linked to the pathology of Alzheimer’s disease (AD). Inhibition or reversal of the Aβ peptide aggregation is a promising therapeutic approach for treating AD. Short peptides that are capable of breaking stacked β-sheets have been shown to inhibit Aβ aggregation. In this work, we will use surface plasmon resonance (SPR) to study the kinetics of the breakage of Aβ aggregates by hexapeptides of different properties. Objectives The aim of this study is to (1) develop SPR as a label-free and facile method to screen short peptides that can effectively dissociate Aβ aggregates, and (2) correlate the physical properties (e.g., hydrophobicity and hydrogen bonding) to the inhibitory efficacy. Background Dementia in the elderly is very common, additionally it has been reported that 60 to 70% of dementia is caused by Alzheimer’s disease (AD). AD is a progressive neurodegenerative disorder that gradually affects the patient’s cognitive functions and eventually causes death. The total prevalence of AD in the United States is estimated at 5.4 million, where 5.2 million cases are documented in people of the age 65 and older.1 Although the cause of AD remains undiscovered, increasing evidence have shown that misfolding of Aβ could be the potential cause.2

Amyloid β(1-42) (Aβ42) is a single 42-redisue peptide created by the cleavage of amyloid precursor protein (APP). It can aggregate into insoluble amyloid plaques in the human brain.3The generally accepted process for Aβ42 aggregation is the conformational transition from the natively unstructured form to β-sheet-rich oligomeric form and subsequent reorganization to form cross-β-sheet fibrils.4-5 A potential therapeutic modality to treat AD is to use inhibitors to prevent Aβ misfolding and aggregation.6-9 A strategy used to combat the aggregation of Aβ is to design inhibitors that work by interfering with the formation of Aβ oligomers, or the clearance of Aβ oligomers.10-12 Various compounds are created as highly potential and clinical agents, such as peptide mimetics,13 polymers,14 and small organic compounds.15 Among them, peptide-based inhibitors are more promising compounds, because they are biocompatible and easy to synthesis. A collaborator of ours, using computational chemistry, has shown that using hexapeptides, which we will refer to as amyloidogenic hexapeptides can prevent aggregation of Aβ. The hypothesis is that these small peptides will bind with the hydrophobic Aβ C-terminus and prevent it from aggregating into amyloid plaques. Typical biochemistry methods of identifying the interactions between Aβ and these hexapeptides cannot provide real time kinetics results at low concentrations. To

overcome this problem, SPR is employed to investigate the binding affinities between Aβ and hexapeptides. We are hoping to find a therapeutic modality to treat AD. Materials and Methods SPR is a powerful optical technique for studying bimolecular interactions due to its high sensitivity and label free detection.16 SPR occurs when the polarized light hit backside of a gold-coated sensor chip through a prism. At the resonance angle, light is absorbed by the electrons onto the gold film, which causes a change in the beam’s reflection known as SPR dip. The shape and location of the SPR dip can then be used to convey information binding or unbinding of molecules or proteins attached to the gold surface.17 In this project, by monitoring this shift vs. time, we will study the binding affinities between Aβ and hexapeptides to verify if computational designed hexapeptides can practically prevent Aβ aggregation. In particular, we will use SPR to perform the kinetic study between Aβ42 and hexapeptides. The experiments we propose are to:

Obtain a homogeneous solution of monometric Aβ42 Aβ42 is purified by following thr basic purification step to obtain a homogeneous solution of monomeric Aβ42 in unstructured conformation. Briefly, Aβ42 is dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP, 99.9%) for two h (1mg/ml), sonicated for 30 min to remove any preexisting aggregates or seeds, and Centrifuged at 4 C at 14000 rpm for 30 min. 75% of the supernatant is subpacked and frozen with liquild nitrogen and then dried with a freeze dryer. The try Aβ42 powder is lyophilized at -80C and then stored in -20C fridge for use. Immobilize monometric Aβ onto self-assembled streptavidin (SA) sensor chip surface Obtain a homogeneous solution of monometric hexapeptides

List of hexapeptides: VYIMIG ITLFWG CTLFWG VTLWWG GTVWWG GILFWG

Determine the binding affinities between designed peptides and Aβ42. Significance

The major significance of this research is to develop biocompatible peptide-based inhibitors for Aβ aggregation. The computational design and experimental verification of hexapeptides could possibly provide a new approach of treatment for over 5.4 million AD patients. Moreover, if this method proves to be viable, it could be applied to other neurodegenerative disorders caused by self-aggregation proteins. Reference (1) Hebert, L. E.; Scherr, P. A.; Bienias, J. L.; Bennett, D. A.; Evans, D. A. Archives of

Neurology, 2003, 60, 1119–22. (2) Wang, Q.; Shah, N.; Zhao, J.; Wang, C.; Zhao, C.; Liu, L.; Li, L., Zhou, F.; Zheng, J. Phys. Chem. Chem. Phys., 2011, 13, 15200-15210.

(3) Hardy, J.; Selkoe, D. J. Science, 2002, 297, 353–356. (4) Ding, F.; Borreguero, J. M.; Buldyrey S. V.; Stanley H. E.; Dokholyan N. V. Proteins, 2003, 53, 220–228. (5) Yanagisawa, K. Biochem Subcell. 2005, 38, 179–202. (6) Yamin, G.; Ruchala P.; Teplow, D. B. Biochemistry 2009, 48, 11329-11331. (7) Soto, P.; Griffin, M. A.; Shea, J. E. Biophys. J. 2007, 93, 3015-3025. (8) Takahashi, T.; Mihara, H. Acc Chem Res, 2008, 41, 1309-1318. (9) Hamaguchi, T.; Ono, K.; Yamada, M. Cell Mol Life Sci, 2006, 63, 1538-1552. (10) Dash, P. K.; Moore, A. N.; Orsi, S. A. Biochem. Biophys. Res. Commun. 2005, 338, 777-782. (11) Asai, M.; Hattori, C.; Iwata, N.; Saido, T. C.; Sasaqawa, N.; Szabó, B.; Hashimoto, Y.; Maruyama, K.; Tanuma, S.; Kiso, Y.; Ishiura, S. J. Neurochemistry, 2006, 96, 533-540. (12) Bacskai, B. J.;, Kajdasz, S. T.; Christie, R. H.; Carter, C.; Games, D.; Seubert, P.; Schenk, D.; Hyman, B. T. Nat. Med., 2001, 7, 369-372. (13) Cleary, J. P.; Walsh, D. M.; Hofmeister, J. J.; Shankar, G. M.; Kuskowski, M. A.; Selkoe, D. J.; Ashe, K. H. Nat Neurosci, 2004, 8, 79-84. (14) Cabaleiro-Lago, C.; Quinlan-Pluck, F.; Lynch, I.; Lindman, S.; Minoque, A. M.; Thulin, E.; Walsh, D.M.; Dawson, K. D.; Linse, S. J Am Chem Soc, 2008, 130, 15437-15443. (15) Jameson, L. P.; Smith, N. W.; Dzyuba, S. V. ACS Chemical Neuroscience, 2012, 3, 807-819. (16) Myszka, D. G. Curr. Opin. Biotechnol, 1997, 8, 50-57. (17) Skoog, D. A.; Holler, F. J.; Nieman, T. A. Principles of Instrumental Analysis; Messina, F.; 5th ed; Saunders College: Orlando, FL, 1998.