Morkos Henen, PhD, MS

Professional Titles

• Assistant Professor -Research

Recognitions

• R21, NIH (2022)

Research Interests

My primary area of research is centered on the application of NMR and other biophysical techniques to investigate biomolecules. My research endeavors are focused on the analysis of proteins and nucleic acids that have therapeutic relevance in disease pathology. Additionally, I possess a keen interest in utilizing synthetic chemistry for fragment-based drug discovery (FBDD) approaches. A significant emphasis of my research activities is directed towards the development of innovative NMR pulse sequences to cater to the diverse needs of scientific investigations.

Publications

• Backbone and side-chain chemical shift assignments of full-length, apo, human Pin1, a phosphoprotein regulator with interdomain allostery
• Extending the Applicability of Exact Nuclear Overhauser Enhancements to Large Proteins and RNA
• High-resolution small RNA structures from exact nuclear Overhauser enhancement measurements without additional restraints
• Efficient Stereospecific Hß2/3 NMR Assignment Strategy for Mid-Size Proteins
• TGF-ß2 uses the concave surface of its extended finger region to bind betaglycan’s ZP domain via three residues specific to TGF-ß and Inhibin-a
• A transient helix in the disordered region of dynein light intermediate chain links the motor to structurally diverse adaptors for cargo transport
• Born A, Henen MA, Vögeli B. Activity and Affinity of Pin1 Variants. Molecules. 2019 Dec 20;25(1). PubMed PMID: 31861908
• Kim SK, Henen MA, Hinck AP. Structural biology of betaglycan and endoglin, membrane-bound co-receptors of the TGF-beta family. Exp Biol Med (Maywood). 2019 Dec;244(17):1547-1558. PubMed PMID: 31601110
• Issaian A, Schmitt L, Born A, Nichols PJ, Sikela J, Hansen K, Vögeli B, Henen MA. Solution NMR backbone assignment reveals interaction-free tumbling of human lineage-specific Olduvai protein domains. Biomol NMR Assign. 2019 Oct;13(2):339-343. PubMed PMID: 31264103
• Celestino R, Henen MA, Gama JB, Carvalho C, McCabe M, Barbosa DJ, Born A, Nichols PJ, Carvalho AX, Gassmann R, Vögeli B. A transient helix in the disordered region of dynein light intermediate chain links the motor to structurally diverse adaptors for cargo transport. PLoS Biol. 2019 Jan;17(1):e3000100. PubMed PMID: 30615611
• Henen MA, Mahlawat P, Zwieb C, Kodali RB, Hinck CS, Hanna RD, Krzysiak TC, Ilangovan U, Cano KE, Hinck G, Vonberg M, McCabe M, Hinck AP. TGF-ß2 uses the concave surface of its extended finger region to bind betaglycan's ZP domain via three residues specific to TGF-ß and inhibin-a. J Biol Chem. 2019 Mar 1;294(9):3065-3080. PubMed PMID: 30598510
• Born A, Nichols PJ, Henen MA, Chi CN, Strotz D, Bayer P, Tate SI, Peng JW, Vögeli B. Backbone and side-chain chemical shift assignments of full-length, apo, human Pin1, a phosphoprotein regulator with interdomain allostery. Biomol NMR Assign. 2019 Apr;13(1):85-89. PubMed PMID: 30353504
• Nashaat S, Henen MA, El-Messery SM, Eisa H. Synthesis, state-of-the-art NMR-binding and molecular modeling study of new benzimidazole core derivatives as Pin1 inhibitors: Targeting breast cancer. Bioorg Med Chem. 2020 Jun 1;28(11):115495. PubMed PMID: 32307260
• Nichols PJ, Born A, Henen MA, Strotz D, Jones DN, Delaglio F, Vögeli B. Reducing the measurement time of exact NOEs by non-uniform sampling. J Biomol NMR. 2020 Dec;74(12):717-739. PubMed PMID: 32880802
• El-Khouly OA, Henen MA, El-Sayed MA, Shabaan MI, El-Messery SM. Synthesis, anticancer and antimicrobial evaluation of new benzofuran based derivatives: PI3K inhibition, quorum sensing and molecular modeling study. Bioorg Med Chem. 2020 Dec 27;31:115976. [Epub ahead of print] PubMed PMID: 33388654
• Born A, Soetbeer J, Breitgoff F, Henen MA, Sgourakis N, Polyhach Y, Nichols PJ, Strotz D, Jeschke G, Vögeli B. Reconstruction of Coupled Intra- and Interdomain Protein Motion from Nuclear and Electron Magnetic Resonance. J Am Chem Soc. 2021 Oct 6;143(39):16055-16067. PubMed PMID: 34579531
• Wang RX, Henen MA, Lee JS, Vögeli B, Colgan SP. Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. Gut Microbes. 2021 Jan-Dec;13(1):1938380. PubMed PMID: 34190032
• Redzic JS, Lee E, Born A, Issaian A, Henen MA, Nichols PJ, Blue A, Hansen KC, D'Alessandro A, Vögeli B, Eisenmesser EZ. The Inherent Dynamics and Interaction Sites of the SARS-CoV-2 Nucleocapsid N-Terminal Region. J Mol Biol. 2021 Jul 23;433(15):167108. PubMed PMID: 34161778
• Alexeev EE, Dowdell AS, Henen MA, Lanis JM, Lee JS, Cartwright IM, Schaefer REM, Ornelas A, Onyiah JC, Vögeli B, Colgan SP. Microbial-derived indoles inhibit neutrophil myeloperoxidase to diminish bystander tissue damage. FASEB J. 2021 May;35(5):e21552. PubMed PMID: 33826788
• Nichols PJ, Henen MA, Vicens Q, Vögeli B. Solution NMR backbone assignments of the N-terminal Za-linker-Zß segment from Homo sapiens ADAR1p150. Biomol NMR Assign. 2021 Oct;15(2):273-279. PubMed PMID: 33742389
• Tengesdal IW, Menon DR, Osborne DG, Neff CP, Powers NE, Gamboni F, Mauro AG, D'Alessandro A, Stefanoni D, Henen MA, Mills TS, De Graaf DM, Azam T, Vogeli B, Palmer BE, Pietras EM, DeGregori J, Tan AC, Joosten LAB, Fujita M, Dinarello CA, Marchetti C. Targeting tumor-derived NLRP3 reduces melanoma progression by limiting MDSCs expansion. Proc Natl Acad Sci U S A. 2021 Mar 9;118(10). PubMed PMID: 33649199
• Nichols PJ, Bevers S, Henen M, Kieft JS, Vicens Q, Vögeli B. Recognition of non-CpG repeats in Alu and ribosomal RNAs by the Z-RNA binding domain of ADAR1 induces A-Z junctions. Nat Commun. 2021 Feb 4;12(1):793. PubMed PMID: 33542240
• Henen MA, Myers W, Schmitt LR, Wade KJ, Born A, Nichols PJ, Vögeli B. The Disordered Spindly C-terminus Interacts with RZZ Subunits ROD-1 and ZWL-1 in the Kinetochore through the Same Sites in C. Elegans. J Mol Biol. 2021 Feb 19;433(4):166812. PubMed PMID: 33450249
• El-Khouly OA, Henen MA, El-Sayed MA, Shabaan MI, El-Messery SM. Synthesis, anticancer and antimicrobial evaluation of new benzofuran based derivatives: PI3K inhibition, quorum sensing and molecular modeling study. Bioorg Med Chem. 2021 Feb 1;31:115976. PubMed PMID: 33388654
• Born A, Henen MA, Nichols P, Wang J, Jones DN, Vögeli B. Efficient Stereospecific H(ß2/3) NMR Assignment Strategy for Mid-Size Proteins. Magnetochemistry. 2018 Jun;4(2). PubMed PMID: 31093488
• Nichols PJ, Henen MA, Born A, Strotz D, Güntert P, Vögeli B. High-resolution small RNA structures from exact nuclear Overhauser enhancement measurements without additional restraints. Commun Biol. 2018;1:61. PubMed PMID: 30271943
• Villarreal MM, Kim SK, Barron L, Kodali R, Baardsnes J, Hinck CS, Krzysiak TC, Henen MA, Pakhomova O, Mendoza V, O'Connor-McCourt MD, Lafer EM, López-Casillas F, Hinck AP. Correction to Binding Properties of the Transforming Growth Factor-ß Coreceptor Betaglycan: Proposed Mechanism for Potentiation of Receptor Complex Assembly and Signaling. Biochemistry. 2017 Jul 18;56(28):3689. PubMed PMID: 28677957
• Byrne C, Henen MA, Belnou M, Cantrelle FX, Kamah A, Qi H, Giustiniani J, Chambraud B, Baulieu EE, Lippens G, Landrieu I, Jacquot Y. A ß-Turn Motif in the Steroid Hormone Receptor's Ligand-Binding Domains Interacts with the Peptidyl-prolyl Isomerase (PPIase) Catalytic Site of the Immunophilin FKBP52. Biochemistry. 2016 Sep 27;55(38):5366-76. PubMed PMID: 27641460
• Villarreal MM, Kim SK, Barron L, Kodali R, Baardsnes J, Hinck CS, Krzysiak TC, Henen MA, Pakhomova O, Mendoza V, O'Connor-McCourt MD, Lafer EM, López-Casillas F, Hinck AP. Binding Properties of the Transforming Growth Factor-ß Coreceptor Betaglycan: Proposed Mechanism for Potentiation of Receptor Complex Assembly and Signaling. Biochemistry. 2016 Dec 13;55(49):6880-6896. PubMed PMID: 27951653
• Milroy LG, Bartel M, Henen MA, Leysen S, Adriaans JM, Brunsveld L, Landrieu I, Ottmann C. Stabilizer-Guided Inhibition of Protein-Protein Interactions. Angew Chem Int Ed Engl. 2015 Dec 21;54(52):15720-4. PubMed PMID: 26537010
• Orbán-Németh Z, Henen MA, Geist L, Zerko S, Saxena S, Stanek J, Kozminski W, Propst F, Konrat R. Backbone and partial side chain assignment of the microtubule binding domain of the MAP1B light chain. Biomol NMR Assign. 2014 Apr;8(1):123-7. PubMed PMID: 23339032
• Geist L, Henen MA, Haiderer S, Schwarz TC, Kurzbach D, Zawadzka-Kazimierczuk A, Saxena S, Zerko S, Kozminski W, Hinderberger D, Konrat R. Protonation-dependent conformational variability of intrinsically disordered proteins. Protein Sci. 2013 Sep;22(9):1196-205. PubMed PMID: 23821606
• Kurzbach D, Platzer G, Schwarz TC, Henen MA, Konrat R, Hinderberger D. Cooperative unfolding of compact conformations of the intrinsically disordered protein osteopontin. Biochemistry. 2013 Aug 6;52(31):5167-75. PubMed PMID: 23848319
• Henen MA, Coudevylle N, Geist L, Konrat R. Toward rational fragment-based lead design without 3D structures. J Med Chem. 2012 Sep 13;55(17):7909-19. PubMed PMID: 22889313
• Henen, M.A., El Bialy, S.A.A., Goda, F.E. et al. [1,2,4]Triazolo[4,3-a]quinoxaline: synthesis, antiviral, and antimicrobial activities. Med Chem Res 21, 2368–2378 (2012). https://doi.org/10.1007/s00044-011-9753-7
• Henen, M.A.; Hamdi, A.; Farahat, A.A.; Massoud, M.A.M. Understanding Chemistry and Unique NMR Characters of Novel Amide and Ester Leflunomide Analogues. Magnetochemistry 2017, 3, 41. https://doi.org/10.3390/magnetochemistry3040041
• Clements CM, Vögeli B, Shellman YG, Henen MA. SAM1 domain of SASH1 harbors distinctive structural heterogeneity. J Struct Biol. 2022 Dec;214(4):107914. PubMed PMID: 36341956
• Kim JS, Born A, Till JKA, Liu L, Kant S, Henen MA, Vögeli B, Vázquez-Torres A. Promiscuity of response regulators for thioredoxin steers bacterial virulence. Nat Commun. 2022 Oct 20;13(1):6210. PubMed PMID: 36266276
• El-Khouly OA, Henen MA, El-Sayed MA, El-Messery SM. Design, synthesis and computational study of new benzofuran hybrids as dual PI3K/VEGFR2 inhibitors targeting cancer. Sci Rep. 2022 Oct 12;12(1):17104. PubMed PMID: 36224254
• Nashaat S, Henen MA, El-Messery SM, Eisa H. New Benzimidazoles Targeting Breast Cancer: Synthesis, Pin1 Inhibition, 2D NMR Binding, and Computational Studies. Molecules. 2022 Aug 17;27(16). PubMed PMID: 36014485
• Hussain A, Paukovich N, Henen MA, Vögeli B. Advances in the exact nuclear Overhauser effect 2018-2022. Methods. 2022 Oct;206:87-98. PubMed PMID: 35985641
• Born A, Soetbeer J, Henen MA, Breitgoff F, Polyhach Y, Jeschke G, Vögeli B. Ligand-specific conformational change drives interdomain allostery in Pin1. Nat Commun. 2022 Aug 4;13(1):4546. PubMed PMID: 35927276
• Born A, Henen MA, Nichols PJ, Vögeli B. On the use of residual dipolar couplings in multi-state structure calculation of two-domain proteins. Magn Reson Lett. 2022 May;2(2):61-68. PubMed PMID: 35734611
• Paukovich N, Henen MA, Hussain A, Issaian A, Sikela JM, Hansen KC, Vögeli B. Solution NMR backbone assignments of disordered Olduvai protein domain CON1 employing Ha-detected experiments. Biomol NMR Assign. 2022 Apr;16(1):113-119. PubMed PMID: 35098449
• Nichols PJ, Krall JB, Henen MA, Welty R, Macfadden A, Vicens Q, Vögeli B. Z-Form Adoption of Nucleic Acid is a Multi-Step Process Which Proceeds through a Melted Intermediate. J Am Chem Soc. 2023 Dec 22. [Epub ahead of print] PubMed PMID: 38131335
• Lambert KA, Clements CM, Mukherjee N, Pacheco TR, Shellman SX, Henen MA, Vögeli B, Goldstein NB, Birlea S, Hintzsche J, Tan AC, Zhao R, Norris DA, Robinson WA, Wang Y, VanTreeck JG, Shellman YG. SASH1 interacts with TNKS2 and promotes human melanocyte stem cell maintenance. bioRxiv. 2023 Sep 27. PubMed PMID: 37808724
• Maurina SF, O'Sullivan JP, Sharma G, Pineda Rodriguez DC, MacFadden A, Cendali F, Henen MA, Vögeli B, Kieft JS, Glasgow A, Steckelberg AL. An Evolutionarily Conserved Strategy for Ribosome Binding and Host Translation Inhibition by ß-coronavirus Non-structural Protein 1. J Mol Biol. 2023 Oct 15;435(20):168259. PubMed PMID: 37660941
• Pacheco A, Issaian A, Davis J, Anderson N, Nemkov T, Paukovich N, Henen MA, Vögeli B, Sikela JM, Hansen K. Proteolytic activation of human-specific Olduvai domains by the furin protease. Int J Biol Macromol. 2023 Apr 15;234:123041. PubMed PMID: 36581038
• Nichols PJ, Krall JB, Henen MA, Vögeli B, Vicens Q. Z-RNA biology: a central role in the innate immune response?. RNA. 2023 Mar;29(3):273-281. PubMed PMID: 36596670
• Krall JB, Nichols PJ, Henen MA, Vicens Q, Vögeli B. Structure and Formation of Z-DNA and Z-RNA. Molecules. 2023 Jan 14;28(2). PubMed PMID: 36677900
• De Silva SM, Dhiman A, Sood S, Mercedes KF, Simmons WJ, Henen MA, Vögeli B, Dykhuizen EC, Musselman CA. PBRM1 bromodomains associate with RNA to facilitate chromatin association. Nucleic Acids Res. 2023 May 8;51(8):3631-3649. PubMed PMID: 36808431
• Langeberg CJ, Nichols PJ, Henen MA, Vicens Q, Vögeli B. Differential Structural Features of Two Mutant ADAR1p150 Za Domains Associated with Aicardi-Goutières Syndrome. J Mol Biol. 2023 Apr 15;435(8):168040. PubMed PMID: 36889460
• Nichols PJ, Bevers S, Henen MA, Kieft JS, Vicens Q, Vögeli B. Adoption of A-Z Junctions in RNAs by Binding of Za Domains. Methods Mol Biol. 2023;2651:251-275. PubMed PMID: 36892773
• Clements CM, Vögeli B, Shellman YG, Henen MA. Solution NMR backbone assignment of the SASH1 SLy proteins associated disordered region (SPIDER). Biomol NMR Assign. 2023 Jun;17(1):151-157. PubMed PMID: 37155029
• Clements CM, Henen MA, Vögeli B, Shellman YG. The Structural Dynamics, Complexity of Interactions, and Functions in Cancer of Multi-SAM Containing Proteins. Cancers (Basel). 2023 Jun 1;15(11). PubMed PMID: 37296980
• Maurina SF, O'Sullivan JP, Sharma G, Pineda Rodriguez DC, MacFadden A, Cendali F, Henen MA, Kieft JS, Glasgow A, Steckelberg AL. An evolutionarily conserved strategy for ribosome binding and inhibition by ß-coronavirus non-structural protein 1. bioRxiv. 2023 Jun 8. PubMed PMID: 37333070
• Henen MA, Paukovich N, Prekeris R, Vögeli B. Solution NMR Backbone Assignment of the C-Terminal Region of Human Dynein Light Intermediate Chain 2 (LIC2-C) Unveils Structural Resemblance with Its Homologue LIC1-C. Magnetochemistry. 2023 Jul;9(7). PubMed PMID: 37476506