Yun Lyna Luo, PhD

• Postdoc, Argonne National Laboratory, US 2011-2013
• Postdoc, University of Chicago, US 2008-2011
• Ph.D. Ecole Normale Supérieure, University of Paris VI, France 2004-2007
• BS. MS. Zhejiang University, China 1997-2004

· Molecular Simulation and Drug Design, 3 Credit Hours

· Pharmacological Basis of Therapeutics I-IV (Medicinal Chemistry topics), 48 Lecture hours/year

· Advanced Pharmaceutical Sciences II (Drug Metabolism, Acid-base Chemistry, Drug Design topics), 12 Lecture hours/year

· Graduate Seminar, 2 Credit Hours, Facilitator

· Interprofessional Practice & Education, Facilitator

As a computational chemistry/biophysics research group, we investigate the structural dynamics of complex biomolecules and conduct mechanism-based drug design.

The ongoing projects are:

Mechanical and chemical gating of mechanosensitive Piezo channels;

Gating and molecular permeation of connexin hemichannels;

Gating mechanism of HCN channels;

Computational method for reversible covalent drug design;

Computational method for protein allosteric network analysis;

Research Grants (active)

NIH R01GM130834 (multi-PI, WesternU) 09/2019-05/2024

Mechanisms of mechanical and chemical gating in mechanosensitive piezo1 channels

NIH R01GM139164 (co-I, U Miami) 05/2021-05/2024

Activation mechanism in HCN channels

NIH R01 (co-I, UC Davis) 04/2022-03/2027

Gating and regulation of connexin hemichannels

Tower Cancer Research Foundation(co-I, City of Hope) 01/2023-12/2027

A Novel Approach to Elicit Anti-tumor Immunity Against Acute Myeloid Leukemia

Research Grants (completed)

U.S. Department of Defense BA170606 (co-I, WesternU) 062019-06/2023

Optimization of a selective calpain-2 inhibitor for prolonged field care in traumatic brain injury

NIH R21NS090397 (multi-PI, WesternU) 07/2015-06/2018

Development of a selective calpain-2 inhibitor for treating learning impairment in Angelman syndrome

City of Hope research contract (PI) 01/2021-01/2023

Virtual screening and lead-optimization of PRMT9 inhibitors

KGI research contract (PI) 08/2020-01/2021

Ion pairing and dielectric decrement in glycosaminoglycan brushes

NSF XSEDE Research Allocation MCB160119 (PI) 04/2016-06/2023

Computational study of mechanosensitive channel and small molecule binding

Pittsburgh Supercomputing Center Anton Allocation MCB190044P (PI) 12/2017-11/2023

Gating mechanism of mechanosensitive Piezo channels

Pittsburgh Supercomputing Center Anton Allocation MCB170106P (PI) 12/2020-11/2021

Molecular selectivity and saturation in a Connexin channel

WesternU Intramural Research Grant (PI) 07/2018-07/2019

Pharmacology and gating mechanism of Piezo channels

Editorial Board Member of Communications Biology -Nature (Computational Biophysics topics) 2022 -

Guest Editor of J Comput Chem, "Membrane Protein Simulations and Free Energy Approaches" Special Issue 2020

Member of

Biophysical Society (BPS)

BPS Membrane Transport Subgroup (Chair-elect 2023)

American Chemical Society (ACS)

ACS Division of Computers in Chemistry (Programing committee 2022)

International Society of Quantum Biology and Pharmacology (ISQBP) (Councilor-elect 2023)

Biophysics Colab (Outreach taskforce 2022)

Society of General Physiologists (SGP)

American Association for the Advancement of Science (AAAS)

American Association of Colleges of Pharmacy (AACP)

Chinese American Faculty Association (CAFA) Southern California (President-elect 2020)

Meeting Organizer of

American Chemical Society Spring Annual Meeting, Molecular Mechanics Sessions, Indianapolis, Mar, 2023

67th Biophysical Society Annual Meeting, Membrane Transport Subgroup Symposium, San Diego, Feb, 2023

67th Biophysical Society Annual Meeting, Mechanosensitive Membrane Protein Platform, San Diego, Feb, 2023

66th Biophysical Society Annual Meeting, Membrane Transport Subgroup Symposium, San Francisco, Feb, 2022

Membrane Protein Simulations and Free Energy Approaches, ACS, Boston, Aug, 2018

Computational Methods to Address Challenges in Drug Discovery, CECAM Workshop, Lausanne, June, 2017

Journal Reviewer of

Nature Communications; Science Advances, eLife; Communication Biology; PNAS, Biophysical Journal; Journal of the American Chemical Society (JACS); Journal of Chemical Theory and Computation (JCTC); Journal of General Physiology (JGP); Journal of Chemical Information and Modeling (JCIM); The Journal of Physical Chemistry B (JPCB).; Journal of Medicinal Chemistry (JMC); The Journal of Chemical Physics (JCP), Journal of Computational Chemistry (JCC); Trends in Biochemical Sciences; PROTEINS: Structure, Function, and Bioinformatics; BBA – Biomembrane;, Scientific Reports; Current Opinion in Structural Biology; European Journal of Medicinal Chemistry; Bioorganic & Medicinal Chemistry Letters; ACS Omega; International Journal of Molecular Science;, Journal of Molecular Graphics and Modeling; Computational Biology and Chemistry; PLOS One; PeerJ; Frontiers Oncology, Computational Biology and Chemistry; Journal of Biomolecular Structure & Dynamics

Grant Proposal Reviewer of

NIH Macromolecular Structure and Function B Study Section - MSFB

ACS Petroleum Research Fund

AACP New Investigator Award Grants

Centre Européen de Calcul Atomique et Moléculaire (CECAM) Workshop Proposals

Natural Sciences and Engineering Research Council (NSERC) of Canada Discovery Grants

College Reward and Recognition Committee (chair 2016-2017)

College Student Performance Committee (chair 2019-2020)

College Tenure and Promotion Committee (chair 2023-2024)

Vice chair of Department of Pharmaceutical Sciences (2018-2019)

University Awards Committee

College Curriculum Committee

College Faculty Secretary

College Peer Evaluation Committee

Master of Science in Pharmaceutical Sciences (MSPS) Admission Committee

MSPS Graduate Program Committee

MSPS Self-Study Committee

Work from WesternU

2023

· Reliability and Reproducibility Checklist for Molecular Dynamics Simulations, Commun Biol2023, 6,268. (Editorial)

· Jiang W, Zhang H, Lin Y, Im W, Lacroix J, Luo Y. Binding Free Energies of Piezo1 Channel Agonists at Protein-Membrane Interface. BioRxiv, doi.org/10.1101/2022.06.27.497657

· Delemotte, L & Luo, Y.,Molecular Dynamics. Handbook ofIon channels, 2nd Edition.

2022-2021

1.Jiang, W.*, Lacroix, J, Luo, Y.*,Importance of molecular dynamics equilibrium protocol on protein-lipid interaction near channel pore,Biophysical Reports, 2022, 2, 100080.

2. Luo Y,Mechanism-Based and Computational-Driven Covalent Drug Design, J. Chem. Inf. Model.2021, 61,5307-5311. (Viewpoint)

3. Lin, Y., Luo, Y.*,Unifying Single-channel permeability from rare-event sampling and steady-state flux,Frontiers in Molecular Biosciences: Biological Modeling and Simulation, 2022.

4. Jiang, W., Del Rosario, J.S., Botello-Smith, W., Zhao, S., Lin, Y., Zhang, Han., Lacroix, J.*, Rohacs, T.*, Luo, Y.*,Crowding-induced opening of the mechanosensitive Piezo1 channel in silico.Commun. Biol.4, 84, 2021

5. Jiang, W., Ling, Y., Luo, Y.*,Mechanical properties of anionic asymmetric bilayers from atomistic simulations,J. Chem. Phys., 2021

6. Jiang, W., Lin, Y., Botello-Smith, W., Contreras, J.*, Harris, A.*, Maragliano, L.*, Luo, Y.*,Free energy and kinetics of cAMP permeation through connexin26 hemichannel via applied voltage and milestoning,Biophys. J.,2021

7. Sterling, J.*, Jiang, W., Botello-Smith, W., Luo, Y.*,Ion pairing and dielectric decrement in glycosaminoglycan brushes,J. Phys. Chem. B., 2021

8. Botello-Smith, W., Luo, Y.,Concepts, practices, and interactive tutorial for allosteric network analysis of molecular dynamics simulations.Methods Mol. Biol. 2021, 2302, 311

9. Luo, Y., Lacroix, J.,Methods & challenges to study mechanosensitive ion channels. In L. Zhou, editor,Ion channels in biophysics and physiology.Springer.

2020

10. Botello-Smith, W, Luo, Y.*, Investigating protein-protein allosteric network using current-flow scheme, J. Comput. Chem, 2020, 41, 552-560

11. Im, W., Banavali, N., Luo, Y., Celebrating benoit Roux’s 60th birthday: quantifying biology at the membrane. J. Comput. Chem, 2020 (Editorial)

12. Gaete PS, Lillo MA, López W, Liu Y, Jiang W, Luo Y, Harris AL, Contreras JE., A novel voltage-clamp/dye uptake assay reveals saturable transport of molecules through CALHM1 and connexin channels, J Gen Physiol. 2020 Nov 2;152(11):e202012607.

13. Anderson, S., Tabassum, A., Yeon, J., Sharma, G., Santos, P., Soong, T., Thu, Y., Nies, I., Kurita, T., Chandler, A., Alsamarah, A., Kanassatega, R., Luo, Y.*, Botello-Smith, W.*, Andresen, B.*, In silico prediction of ARB resistance: A first step in creating personalized ARB therapy. PLOS Comput. Biol., 2020.

14. Xie, C.; Jiang, W.; Lacroix, J.J.;Luo, Y.*; Hao, J*. Insight into Molecular Mechanism for Activin A-Induced Bone Morphogenetic Protein Signaling.Int. J. Mol. Sci.2020,21, 6498.

15. Sun J, Liu Y, Zhu G, Cato C, Hao X, Qian L, Lin W, Adhikari R,Luo Y, Baudry M, Bi X., PKA and Ube3a regulate SK2 channel trafficking to promote synaptic plasticity in hippocampus: Implications for Angelman Syndrome,Sci. Rep.2020, 10, 9824.

2019

16. Botello-Smith W, Zhang H, Ozkan AD, Jiang W, Pham CN, Lacroix J* and Luo Y*, A molecular Mechanism for the Chemical Activation of the Mechanosensitive Piezo1 Channel, Nat. Commun., DOI: 10.1038/s41467-019-12501-1.

17. Zhu Y, He X, Lin YC, Dong H, Zhang L, Chen X, Wang Z, Shen Y, Li M, Wang H, Sun J, Nguyen LX, Zhang H, Jiang W, Yang Y, Chen J, Müschen M, Chen CW, Konopleva MY, Sun W, Jin J, Carlesso N, Marcucci G, Luo Y, Li L., Targeting PRMT1-mediated FLT3 methylation disrupts maintenance of MLL-rearranged acute lymphoblastic leukemia, Blood, DOI: 10.1182/blood.2019002457.

18. Botello-Smith, W., Luo, Y.*, Robust determination of protein allosteric signaling pathways, J. Chem. Theory Comput., 2019, 15, 2116-2126.

19. Capuccino, J., Chatterjee, P., Garcia, I., Botello-Smith, W., Zhang, H., Harris, A., Luo, Y.*, Contreras, J.*, The connexin26 human mutation N14K disrupts cytosolic intersubunit interactions and promotes channel opening, J. Gen. Physiol., 2019, 151, 382-341.

20. Zhang, H., Jiang, W., Chatterjee P., Luo, Y.*, Ranking reversible covalent drugs: from free energy perturbation to fragment docking, J. Chem. Inf. Model, 2019, 59, 2093-2102.

21. He X, Zhu Y, Lin YC, Li M, Du J, Dong H, Sun J, Zhu L, Wang H, Ding Z, Zhang L, Zhang L, Zhao D, Wang Z, Wu H, Zhang H, Jiang W, Xu Y, Jin J, Shen Y, Perry J, Zhao X, Zhang B, Liu S, Xue SL, Shen B, Chen CW, Chen J, Khaled S, Kuo YH, Marcucci G, Luo Y, Li L., PRMT1-mediated FLT3 arginine methylation promotes maintenance of FLT3-ITD+ acute myeloid leukemia, Blood, 2019, 134, 548-560.

2018

22. Lacroix, J.*, Botello-Smith, W., Luo, Y., Probing the gating mechanism of the mechanosensitive channel Piezo1 with the small molecule Yoda1, Nat. Commun., 2018, 9, 2029.

23. Q. Fei, D. Kent, W. Botello-Smith, F. Nur, S. Nur, A. Alsamarah, P. Chatterjee, M. Lambros*, Y. Luo*, Molecular mechanism of resveratrol’s lipid membrane protection, Sci. Rep., 2018, 8, 1587.

24. Abrams CK, Peinado A, Mahmoud R, Bocarsly M, Zhang H, Chang P, Botello-Smith WM, Freidin MM, Luo Y., Alterations at Arg76 of human connexin 46, a residue associated with cataract formation, cause loss of gap junction formation but preserve hemichannel function. Am. J. Physiol. Cell Physiol.2018, 315, 623-635.

25. Chatterjee, P., Yadav, M., Chauhan, N., Huang, Y., Luo, Y., Cancer cell metabolism featuring Nrf2. Curr. Drug Discov. Technol. 2018, doi: 10.2174/1570163815666180911092443.

26. M. Liu, K. Huang, L. Qian, P. Chatterjee, S. Zhang, R. Li, S. Zhou, Z. Wang, Y. Luo, Y. Huang, Effects of bioactive constituents in the Traditional Chinese Medicinal formula Si-Wu-Tang on Nrf2 signaling and neoplastic cellular transformation, Phytomedicine, 2018, 40, 1-9.

2017

27. P. Chatterjee,W. Botello-Smith,H. Zhang,L Qian,A. Alsamarah,D. Kent,J. Lacroix,M. Baudry,Y. Luo*,Can relative binding free energy predict selectivity of reversible covalent inhibitors?J. Am. Chem. Soc.2017, 139, 17945-17952.

28. W. Botello-Smith, A. Alsamarah, P. Chatterjee, C. Xie, J.J. Lacroix, J.Hao*, Y. Luo*, Polymodal allosteric regulation of type 1 serine/threonine kinase receptors via a conserved electrostatic lock, PLOS Comput. Biol.,2017, 13, e1005711.

2016

29. Y. Luo*, A. R. Rossi, A. L. Harris, Computational Studies of Molecular Permeation through Connexin26 Channels, Biophys. J., 2016, 110, 584-599.

30. W. Lopez, J. Ramachandran, A. Alsamarah, Y. Luo, A. L. Harris, and J. E. Contreras, Mechanism of gating by calcium in connexin hemichannels, Proc. Natl. Acad. Sci. U S A,2016, 113, E7986-E7995.

31. Y. Luo*, A. Alsamarah, K. Zhang, J. Hao*. Development of New Therapeutic Agents for Fibrodysplasia Ossificans Progressiva. Curr Mol Med., 2016, 16, 4-11.

2015

32. A. Alsamarah, AE, LaCuran, P. Oelschlaeger, J. Hao, Y. Luo*, Uncovering molecular bases underlying bone morphogenetic protein receptor inhibitor selectivity. PLOS ONE, 2015, 10, e0132221.

33. J. Sun, G. Zhu, Y. Liu, S. Standley, A. Ji, R. Tunuguntla, Y. Wang, C. Claus, Y. Luo, M. Baudry, X. Bi, UBE3A regulates synaptic plasticity and learning and memory by controlling SK2 channel endocytosis. Cell Rep., 2015, 12, 359-360.

34. Y. Luo*, J. Lacroix, S. Prabhu. Antibody-Drug Conjugates: The 21st Century Magic Bullets for Cancer, Section V Case Studies, Chapter 12: Ado-Trastuzumab Emtansine, Springer, 2015.

Patent

35. M. Baudry, Y. Luo, N. Peet, Calpain-2 selective inhibitors, Full Patent Application; No. PCT/US2015/06015.

Work Before WesternU

36. W. Jiang, J. C. Phillips, L. Huang, M. Fajer, Y. Meng, J. C. Gumbart, Y. Luo, K. Schulten, B. Roux, Generalized scalable multiple copy algorithms for molecular dynamics simulations in NAMD. Comput. Phys. Commun., 2014, 185 (3), 908-916.

37. R. M. Venable, Y. Luo, K. Gawrisch, B. Roux, R. W. Pastor, Simulations of Anionic Lipid Membranes: Development of Interaction-Specific Ion Parameters and Validation Using NMR Data. J. Phys. Chem. B. 2013 117 (35), 10183-10192.

38. P. E. M. Lopes, J. Huang, J. Shim, Y. Luo, H. Li, B. Roux and A. D. MacKerell, Jr., Polarizable Force field for peptides and protein based the Classical Drude Oscillator. J. Chem. Theory Comput., 2013 9 (12), 5430-5449.

39. Y. Luo, W. Jiang, H. Yu, A. D. MacKerell, Jr., and B. Roux, Calibrating the potential function for accurate ion pairing in molecular dynamics simulations of concentration electrolytes solutions. Faraday Discussions, 2013, 160, 135-149.

40. W. Jiang, Y. Luo (co-1st), L. Maragliano, B. Roux, Calculation of Free Energy Landscape in Multi-Dimensions with Hamiltonian-Exchange Umbrella Sampling on Petascale Supercomputer. J. Chem. Theory Comput., 2012, 8 (11), 4672-4680.

41. Y. Luo, E. Harder, R. S. Faibish and B. Roux, Computer simulations of water flux and salt permeability of the reverse osmosis FT-30 aromatic polyamide membrane. J. Mem. Sci. 2011, 384 (1-2), 1-9.

42. J. Herrou, G. Rotskoff, Y. Luo, B. Roux and S. Crosson, The structural basis of a protein partner switch that regulates stress-dependent transcription. Proc. Natl. Acad. Sci. U S A, 2012, 109 (21): E1415-23.

43. Y. Luo and B. Roux, Simulation of osmotic pressure in concentrated aqueous salt solutions. J. Phys. Chem. Lett. 2010, 1 (1), 183–189

44. Y. Luo, B. Egwolf, D. E. Walters, and B. Roux, Ion selectivity of alpha-hemolysin with beta-cyclodextrin adapter: I. Single ion potential of mean force calculations and diffusion coefficient. J. Phys. Chem. B, 2010, 114 (2), 952–958

45. B. Egwolf, Y. Luo, D. E. Walters, and B, Roux, Ion selectivity of alpha-hemolysin with beta-cyclodextrin adapter:II. Multi ion effects studies with grand canonical monte carlo/brownian dynamics simulations. J. Phys. Chem. B, 2010, 114 (8), 2901–2909

46. Y. Luo, F. Barbault, C. Gourmala, Y. M. Zhang, F. Maurel, Y. Z. Hu and B. T. Fan, Cellular interaction through LewisX cluster: theoretical studies.J. Mol. Model, 2008, 14, 901-910.

47. C. Gourmala, Y. Luo, F. Barbault, Y. M. Zhang, S. Ghalem, F. Maurel and B. T. Fan, Elucidation of the LewisX-LewisX carbohydrate interaction with molecular dynamics simulations. J. Mol. Struct.: THEOCHEM, 2007, 821, 22-29.

48. F. Barbault, J. Rebehmed, C. Teixeira, Y. Luo, O. Smila-Castro, F. Maurel, B. T. Fan, Flexible computational docking studies of new aminoglycosides targeting RNA 16S bacterial ribosome site. Eur. J. Med. Chem. 2008, 43, 1648-56.

49. Y. Luo, C. Gourmala, D. Dong, F. Barbault, B. T. Fan, Y. Z. Hu, Y. M. Zhang*, First synthesis of two deoxy Lewisx pentaosyl glycosphingolipids. Glycoconjugate J., 2008, 25, 335-344.

50. Y. Luo, D. X. Dong, F. Barbault, B. T. Fan, Y. Z. Hu, Y. M. Zhang, Total synthesis of 4d-deoxy Lewisx pentasaccharide. Comptes Rendus Chimie, 2008, 11, 29-37.

51. Y. Luo, Y. Z. Hu, Synthesis and Antifungal Activity of 2-Aryl-1,2,4-triazolo[1,5-a]pyridine Derivatives. Archiv der Pharmazie, 2006, 339, 262-266.

52. Gourmala C.; Zhu Z. Y.; Luo Y.; Fan B. T.; Ghalem S.; Hu Y. Z.; Zhang Y. M. First synthesis of 3’-deoxy Lewisx pentasaccharide. Tetrahedron: Asymmetry 2005, 16, 3024-3029.

53. Y. Luo, Y. Z. Hu, Synthesis of 1- (2′-bromo-2′-deoxy-3′,5′-di-O-propionyl-β-D-ribosyl) thymidine. Chin. J. Modern Applied Pharmacy 2004, 21,197-198.

54. Y. Luo, Y. Z. Hu, A Novel and Efficient Strategy for the Preparation of 2,4-disubstituted -1,2,3-triazoles. Synth. Commun., 2003, 33, 3513-3517.

55. Y. Luo, Y. Z. Hu, Cyclin-dependent kinase inhibitor: Novel approaches for cancer therapy. Chin. J. Modern Applied Pharmacy 2003, 20, 360-363.