Aashish Manglik, MD, PhD
Associate Professor
Pharmaceutical Chemistry
School of Pharmacy

To gain a fundamental understanding of such transmembrane signaling processes, we use a diverse array of techniques spanning biochemical and biophysical interrogation to protein engineering. Our ultimate goal is to use these insights to discover new approaches to precisely control cellular signaling.

• Structural Basis of μ-Opioid Receptor-Targeting by a Nanobody Antagonist.
  bioRxiv : the preprint server for biology 2023 Yu J, Kumar A, Zhang X, Martin C, Raia P, Koehl A, Laeremans T, Steyaert J, Manglik A, Ballet S, Boland A, Stoeber M
• Engineered odorant receptors illuminate structural principles of odor discrimination.
  bioRxiv : the preprint server for biology 2023 de March CA, Ma N, Billesbølle CB, Tewari J, Del Torrent CL, van der Velden WJC, Ojiro I, Takayama I, Faust B, Li L, Vaidehi N, Manglik A, Matsunami H
• Rare antibody phage isolation and discrimination (RAPID) biopanning enables identification of high-affinity antibodies against challenging targets.
  Communications biology 2023 Chung DH, Kong S, Young NJ, Chuo SW, Shiah JV, Connelly EJ, Rohweder PJ, Born A, Manglik A, Grandis JR, Johnson DE, Craik CS
• Structure-based discovery of conformationally selective inhibitors of the serotonin transporter.
  Cell 2023 Singh I, Seth A, Billesbølle CB, Braz J, Rodriguiz RM, Roy K, Bekele B, Craik V, Huang XP, Boytsov D, Pogorelov VM, Lak P, O'Donnell H, Sandtner W, Irwin JJ, Roth BL, Basbaum AI, Wetsel WC, Manglik A,…
• Structural basis of odorant recognition by a human odorant receptor.
  Nature 2023 Billesbølle CB, de March CA, van der Velden WJC, Ma N, Tewari J, Del Torrent CL, Li L, Faust B, Vaidehi N, Matsunami H, Manglik A
• Discrete GPCR-triggered endocytic modes enable β-arrestins to flexibly regulate cell signaling.
  eLife 2022 Barsi-Rhyne B, Manglik A, von Zastrow M
• Autoantibody mimicry of hormone action at the thyrotropin receptor.
  Nature 2022 Faust B, Billesbølle CB, Suomivuori CM, Singh I, Zhang K, Hoppe N, Pinto AFM, Diedrich JK, Muftuoglu Y, Szkudlinski MW, Saghatelian A, Dror RO, Cheng Y, Manglik A
• Fusion protein strategies for cryo-EM study of G protein-coupled receptors.
  Nature communications 2022 Zhang K, Wu H, Hoppe N, Manglik A, Cheng Y
• Biochemical Assays to Directly Assess Smoothened Activation by a Conformationally Sensitive Nanobody.
  Methods in molecular biology (Clifton, N.J.) 2022 Deshpande I, Manglik A
• Selective G protein signaling driven by substance P-neurokinin receptor dynamics.
  Nature chemical biology 2021 Harris JA, Faust B, Gondin AB, Dämgen MA, Suomivuori CM, Veldhuis NA, Cheng Y, Dror RO, Thal DM, Manglik A
• CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes.
  Research square 2021 Gupta M, Azumaya CM, Moritz M, Pourmal S, Diallo A, Merz GE, Jang G, Bouhaddou M, Fossati A, Brilot AF, Diwanji D, Hernandez E, Herrera N, Kratochvil HT, Lam VL, Li F, Li Y, Nguyen HC, Nowotny C, …
• CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes.
  bioRxiv : the preprint server for biology 2021 Gupta M, Azumaya CM, Moritz M, Pourmal S, Diallo A, Merz GE, Jang G, Bouhaddou M, Fossati A, Brilot AF, Diwanji D, Hernandez E, Herrera N, Kratochvil HT, Lam VL, Li F, Li Y, Nguyen HC, Nowotny C, …
• Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia.
  Cell 2021 Asarnow D, Wang B, Lee WH, Hu Y, Huang CW, Faust B, Ng PML, Ngoh EZX, Bohn M, Bulkley D, Pizzorno A, Ary B, Tan HC, Lee CY, Minhat RA, Terrier O, Soh MK, Teo FJ, Yeap YYC, Seah SGK, Chan CEZ, Connelly…
• Protein design and variant prediction using autoregressive generative models.
  Nature communications 2021 Shin JE, Riesselman AJ, Kollasch AW, McMahon C, Simon E, Sander C, Manglik A, Kruse AC, Marks DS
• Smoothened transduces Hedgehog signals via activity-dependent sequestration of PKA catalytic subunits.
  PLoS biology 2021 Arveseth CD, Happ JT, Hedeen DS, Zhu JF, Capener JL, Klatt Shaw D, Deshpande I, Liang J, Xu J, Stubben SL, Nelson IB, Walker MF, Kawakami K, Inoue A, Krogan NJ, Grunwald DJ, Hüttenhain R, Manglik A, …
• Surface Proteomics Reveals CD72 as a Target for In Vitro-Evolved Nanobody-Based CAR-T Cells in KMT2A/MLL1-Rearranged B-ALL.
  Cancer discovery 2021 Nix MA, Mandal K, Geng H, Paranjape N, Lin YT, Rivera JM, Marcoulis M, White KL, Whitman JD, Bapat SP, Parker KR, Ramirez J, Deucher A, Phojanokong P, Steri V, Fattahi F, Hann BC, Satpathy AT, Manglik…
• An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike.
  Science (New York, N.Y.) 2020 Schoof M, Faust B, Saunders RA, Sangwan S, Rezelj V, Hoppe N, Boone M, Billesbølle CB, Puchades C, Azumaya CM, Kratochvil HT, Zimanyi M, Deshpande I, Liang J, Dickinson S, Nguyen HC, Chio CM, Merz GE,…
• Hedgehog pathway activation through nanobody-mediated conformational blockade of the Patched sterol conduit.
  Proceedings of the National Academy of Sciences of the United States of America 2020 Zhang Y, Lu WJ, Bulkley DP, Liang J, Ralko A, Han S, Roberts KJ, Li A, Cho W, Cheng Y, Manglik A, Beachy PA
• Universal Polymerase Chain Reaction and Antibody Testing Demonstrate Little to No Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 in a Rural Community.
  Open forum infectious diseases 2020 Appa A, Takahashi S, Rodriguez-Barraquer I, Chamie G, Sawyer A, Duarte E, Hakim J, Turcios K, Vinden J, Janson O, Manglik A, Peluso MJ, Deeks SG, Henrich TJ, Torres L, Rodgers M, Hackett J, Chiu C, …
• Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.
  Science (New York, N.Y.) 2020 Gordon DE, Hiatt J, Bouhaddou M, Rezelj VV, Ulferts S, Braberg H, Jureka AS, Obernier K, Guo JZ, Batra J, Kaake RM, Weckstein AR, Owens TW, Gupta M, Pourmal S, Titus EW, Cakir M, Soucheray M, McGregor…
• Evaluation of SARS-CoV-2 serology assays reveals a range of test performance.
  Nature biotechnology 2020 Whitman JD, Hiatt J, Mowery CT, Shy BR, Yu R, Yamamoto TN, Rathore U, Goldgof GM, Whitty C, Woo JM, Gallman AE, Miller TE, Levine AG, Nguyen DN, Bapat SP, Balcerek J, Bylsma SA, Lyons AM, Li S, Wong …
• Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms.
  Nature 2020 Billesbølle CB, Azumaya CM, Kretsch RC, Powers AS, Gonen S, Schneider S, Arvedson T, Dror RO, Cheng Y, Manglik A
• An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation.
  bioRxiv : the preprint server for biology 2020 Schoof M, Faust B, Saunders RA, Sangwan S, Rezelj V, Hoppe N, Boone M, Billesbølle CB, Puchades C, Azumaya CM, Kratochvil HT, Zimanyi M, Deshpande I, Liang J, Dickinson S, Nguyen HC, Chio CM, Merz GE,…
• Universal PCR and antibody testing demonstrate little to no transmission of SARS-CoV-2 in a rural community.
  medRxiv : the preprint server for health sciences 2020 Appa A, Takahashi S, Rodriguez-Barraquer I, Chamie G, Sawyer A, Consortium C, Duarte E, Hakim J, Turcios K, Vinden J, Janson O, Manglik A, Peluso MJ, Deeks SG, Henrich TJ, Torres L, Rodgers M, Hackett…
• Author Correction: Structural insights into μ-opioid receptor activation.
  Nature 2020 Huang W, Manglik A, Venkatakrishnan AJ, Laeremans T, Feinberg EN, Sanborn AL, Kato HE, Livingston KE, Thorsen TS, Kling RC, Granier S, Gmeiner P, Husbands SM, Traynor JR, Weis WI, Steyaert J, Dror RO,…
• Bivalent binding of a fully human IgG to the SARS-CoV-2 spike proteins reveals mechanisms of potent neutralization.
  bioRxiv : the preprint server for biology 2020 Wang B, Asarnow D, Lee WH, Huang CW, Faust B, Ng PML, Ngoh EZX, Bohn M, Bulkley D, Pizzorno A, Tan HC, Lee CY, Minhat RA, Terrier O, Soh MK, Teo FJ, Yeap YYC, Hu Y, Seah SGK, Maurer-Stroh S, Renia L, …
• β-Arrestin-Biased Angiotensin II Receptor Agonists for COVID-19.
  Circulation 2020 Manglik A, Wingler LM, Rockman HA, Lefkowitz RJ
• Agonist-selective recruitment of engineered protein probes and of GRK2 by opioid receptors in living cells.
  eLife 2020 Stoeber M, Jullié D, Li J, Chakraborty S, Majumdar S, Lambert NA, Manglik A, von Zastrow M
• Molecular Basis of Opioid Action: From Structures to New Leads.
  Biological psychiatry 2019 Manglik A
• Smoothened stimulation by membrane sterols drives Hedgehog pathway activity.
  Nature 2019 Deshpande I, Liang J, Hedeen D, Roberts KJ, Zhang Y, Ha B, Latorraca NR, Faust B, Dror RO, Beachy PA, Myers BR, Manglik A
• Development of an antibody fragment that stabilizes GPCR/G-protein complexes.
  Nature communications 2018 Maeda S, Koehl A, Matile H, Hu H, Hilger D, Schertler GFX, Manglik A, Skiniotis G, Dawson RJP, Kobilka BK
• Measuring ligand efficacy at the mu-opioid receptor using a conformational biosensor.
  eLife 2018 Livingston KE, Mahoney JP, Manglik A, Sunahara RK, Traynor JR
• Structure of the µ-opioid receptor-Gi protein complex.
  Nature 2018 Koehl A, Hu H, Maeda S, Zhang Y, Qu Q, Paggi JM, Latorraca NR, Hilger D, Dawson R, Matile H, Schertler GFX, Granier S, Weis WI, Dror RO, Manglik A, Skiniotis G, Kobilka BK
• A Genetically Encoded Biosensor Reveals Location Bias of Opioid Drug Action.
  Neuron 2018 Stoeber M, Jullié D, Lobingier BT, Laeremans T, Steyaert J, Schiller PW, Manglik A, von Zastrow M
• Sortase ligation enables homogeneous GPCR phosphorylation to reveal diversity in β-arrestin coupling.
  Proceedings of the National Academy of Sciences of the United States of America 2018 Staus DP, Wingler LM, Choi M, Pani B, Manglik A, Kruse AC, Lefkowitz RJ
• Yeast surface display platform for rapid discovery of conformationally selective nanobodies.
  Nature structural & molecular biology 2018 McMahon C, Baier AS, Pascolutti R, Wegrecki M, Zheng S, Ong JX, Erlandson SC, Hilger D, Rasmussen SGF, Ring AM, Manglik A, Kruse AC
• Structural Basis for G Protein-Coupled Receptor Activation.
  Biochemistry 2017 Manglik A, Kruse AC
• Directed evolution of nanobody chaperones that stabilize GPCR:G-protein complexes.
  The FASEB Journal 2017 Aashish Manglik, Andrew C. Kruse, Antoine Koehl, Brian K. Kobilka, Aaron M. Ring
• Nanobodies to Study G Protein-Coupled Receptor Structure and Function.
  Annual review of pharmacology and toxicology 2016 Manglik A, Kobilka BK, Steyaert J
• Structure-based discovery of opioid analgesics with reduced side effects.
  Nature 2016 Manglik A, Lin H, Aryal DK, McCorvy JD, Dengler D, Corder G, Levit A, Kling RC, Bernat V, Hübner H, Huang XP, Sassano MF, Giguère PM, Löber S, Scherrer G, Kobilka BK, Gmeiner P, Roth BL, Shoichet BK
• Allosteric nanobodies reveal the dynamic range and diverse mechanisms of G-protein-coupled receptor activation.
  Nature 2016 Staus DP, Strachan RT, Manglik A, Pani B, Kahsai AW, Kim TH, Wingler LM, Ahn S, Chatterjee A, Masoudi A, Kruse AC, Pardon E, Steyaert J, Weis WI, Prosser RS, Kobilka BK, Costa T, Lefkowitz RJ
• Allosteric coupling from G protein to the agonist-binding pocket in GPCRs.
  Nature 2016 DeVree BT, Mahoney JP, Vélez-Ruiz GA, Rasmussen SG, Kuszak AJ, Edwald E, Fung JJ, Manglik A, Masureel M, Du Y, Matt RA, Pardon E, Steyaert J, Kobilka BK, Sunahara RK
• Crystal structure of the human σ1 receptor.
  Nature 2016 Schmidt HR, Zheng S, Gurpinar E, Koehl A, Manglik A, Kruse AC
• Efficacy at the Mu Opioid Receptor: Insights from Orthosteric and Allosteric Ligands.
  The FASEB Journal 2016 Kathryn E Livingston, Jacob Mahoney, Aashish Manglik, Brian Kobilka, Roger Sunahara, John R Traynor
• Structural Basis for Allosteric Coupling Between G Protein and the Agonist-Binding Pocket in GPCRs.
  The FASEB Journal 2016 Jacob Mahoney, Brian DeVree, Gisselle Velez-Ruiz, Soren Rasmussen, Adam Kuszak, Elin Edwald, Aashish Manglik, Matthieu Masureel, Yang Du, Rachel Matt, Els Pardon, Jan Steyaert, Brian Kobilka, Roger …
• Abstract B101: Engineered PD-1 variants as immunotherapies for cancer.
  Imaging and Targeting of the Antitumor Response 2016 Sydney R. Gordon, Roy Maute, Aaron Mayer, Melissa McCracken, Arutselvan Natarajan, Nan Guo, Richard Kimura, Jonathan M. Tsai, Aashish Manglik, Andrew Kruse, Sanjiv Gambhir, Irving L. Weissman, Aaron M…
• High-density grids for efficient data collection from multiple crystals.
  Acta crystallographica. Section D, Structural biology 2016 Baxter EL, Aguila L, Alonso-Mori R, Barnes CO, Bonagura CA, Brehmer W, Brunger AT, Calero G, Caradoc-Davies TT, Chatterjee R, Degrado WF, Fraser JS, Ibrahim M, Kern J, Kobilka BK, Kruse AC, Larsson KM…
• Engineering high-affinity PD-1 variants for optimized immunotherapy and immuno-PET imaging.
  Proceedings of the National Academy of Sciences of the United States of America 2015 Maute RL, Gordon SR, Mayer AT, McCracken MN, Natarajan A, Ring NG, Kimura R, Tsai JM, Manglik A, Kruse AC, Gambhir SS, Weissman IL, Ring AM
• Structural Insights into the Dynamic Process of ß2-Adrenergic Receptor Signaling.
  Cell 2015 Aashish Manglik, Tae Hun Kim, Matthieu Masureel, Christian Altenbach, Zhongyu Yang, Daniel Hilger, Michael T. Lerch, Tong Sun Kobilka, Foon Sun Thian, Wayne L. Hubbell, R. Scott Prosser, Brian K. …
• Propagation of conformational changes during μ-opioid receptor activation.
  Nature 2015 Sounier R, Mas C, Steyaert J, Laeremans T, Manglik A, Huang W, Kobilka BK, Déméné H, Granier S
• Structural insights into µ-opioid receptor activation.
  Nature 2015 Huang W, Manglik A, Venkatakrishnan AJ, Laeremans T, Feinberg EN, Sanborn AL, Kato HE, Livingston KE, Thorsen TS, Kling RC, Granier S, Gmeiner P, Husbands SM, Traynor JR, Weis WI, Steyaert J, Dror RO,…
• SIGNAL TRANSDUCTION. Structural basis for nucleotide exchange in heterotrimeric G proteins.
  Science (New York, N.Y.) 2015 Dror RO, Mildorf TJ, Hilger D, Manglik A, Borhani DW, Arlow DH, Philippsen A, Villanueva N, Yang Z, Lerch MT, Hubbell WL, Kobilka BK, Sunahara RK, Shaw DE
• Structural Insights into the Dynamic Process of β2-Adrenergic Receptor Signaling.
  Cell 2015 Manglik A, Kim TH, Masureel M, Altenbach C, Yang Z, Hilger D, Lerch MT, Kobilka TS, Thian FS, Hubbell WL, Prosser RS, Kobilka BK
• A comparison of chemical shift sensitivity of trifluoromethyl tags: optimizing resolution in ¹⁹F NMR studies of proteins.
  Journal of biomolecular NMR 2015 Ye L, Larda ST, Frank Li YF, Manglik A, Prosser RS
• G Protein-coupled Receptor Kinases of the GRK4 Protein Subfamily Phosphorylate Inactive G Protein-coupled Receptors (GPCRs).
  The Journal of biological chemistry 2015 Li L, Homan KT, Vishnivetskiy SA, Manglik A, Tesmer JJ, Gurevich VV, Gurevich EV
• Goniometer-based femtosecond crystallography with X-ray free electron lasers.
  Proceedings of the National Academy of Sciences of the United States of America 2014 Cohen AE, Soltis SM, González A, Aguila L, Alonso-Mori R, Barnes CO, Baxter EL, Brehmer W, Brewster AS, Brunger AT, Calero G, Chang JF, Chollet M, Ehrensberger P, Eriksson TL, Feng Y, Hattne J, Hedman…
• Covalent agonists for studying G protein-coupled receptor activation.
  Proceedings of the National Academy of Sciences of the United States of America 2014 Weichert D, Kruse AC, Manglik A, Hiller C, Zhang C, Hübner H, Kobilka BK, Gmeiner P
• The role of protein dynamics in GPCR function: insights from the β2AR and rhodopsin.
  Current opinion in cell biology 2014 Manglik A, Kobilka B
• Activation and allosteric modulation of a muscarinic acetylcholine receptor.
  Nature 2013 Kruse AC, Ring AM, Manglik A, Hu J, Hu K, Eitel K, Hübner H, Pardon E, Valant C, Sexton PM, Christopoulos A, Felder CC, Gmeiner P, Steyaert J, Weis WI, Garcia KC, Wess J, Kobilka BK
• Applications of molecular replacement to G protein-coupled receptors.
  Acta crystallographica. Section D, Biological crystallography 2013 Kruse AC, Manglik A, Kobilka BK, Weis WI
• Adrenaline-activated structure of β2-adrenoceptor stabilized by an engineered nanobody.
  Nature 2013 Ring AM, Manglik A, Kruse AC, Enos MD, Weis WI, Garcia KC, Kobilka BK
• The role of ligands on the equilibria between functional states of a G protein-coupled receptor.
  Journal of the American Chemical Society 2013 Kim TH, Chung KY, Manglik A, Hansen AL, Dror RO, Mildorf TJ, Shaw DE, Kobilka BK, Prosser RS
• Structure of active β-arrestin-1 bound to a G-protein-coupled receptor phosphopeptide.
  Nature 2013 Shukla AK, Manglik A, Kruse AC, Xiao K, Reis RI, Tseng WC, Staus DP, Hilger D, Uysal S, Huang LY, Paduch M, Tripathi-Shukla P, Koide A, Koide S, Weis WI, Kossiakoff AA, Kobilka BK, Lefkowitz RJ
• Corrigendum: A New Class of Amphiphiles Bearing Rigid Hydrophobic Groups for Solubilization and Stabilization of Membrane Proteins.
  Chemistry - A European Journal 2013 Pil Seok Chae, Søren G. F. Rasmussen, Rohini R. Rana, Kamil Gotfryd, Andrew C. Kruse, Aashish Manglik, Kyung Ho Cho, Shailika Nurva, Ulrik Gether, Lan Guan, Claus J. Loland, Bernadette Byrne, Brian K.…
• Crystal structure of active Beta-arrestin1 bound to phosphorylated carboxy-terminus of a G protein-coupled receptor.
  The FASEB Journal 2013 Arun K. Shukla, Aashish Manglik, Andrew Kruse, Rosana Reis, Wei Chou Tseng, Dean P. Staus, Daniel Hilger, Serdar Uysal, LiYin Huang, Marcin Peduch, Prachi Tripathi-Shukla, Akiko Koide, Shohei Koide, …
• The dynamic process of β(2)-adrenergic receptor activation.
  Cell 2013 Nygaard R, Zou Y, Dror RO, Mildorf TJ, Arlow DH, Manglik A, Pan AC, Liu CW, Fung JJ, Bokoch MP, Thian FS, Kobilka TS, Shaw DE, Mueller L, Prosser RS, Kobilka BK
• Role of detergents in conformational exchange of a G protein-coupled receptor.
  The Journal of biological chemistry 2012 Chung KY, Kim TH, Manglik A, Alvares R, Kobilka BK, Prosser RS
• Inside Cover: A New Class of Amphiphiles Bearing Rigid Hydrophobic Groups for Solubilization and Stabilization of Membrane Proteins (Chem. Eur. J. 31/2012).
  Chemistry - A European Journal 2012 Pil Seok Chae, Søren G. F. Rasmussen, Rohini R. Rana, Kamil Gotfryd, Andrew C. Kruse, Aashish Manglik, Kyung Ho Cho, Shailika Nurva, Ulrik Gether, Lan Guan, Claus J. Loland, Bernadette Byrne, Brian K.…
• A new class of amphiphiles bearing rigid hydrophobic groups for solubilization and stabilization of membrane proteins.
  Chemistry (Weinheim an der Bergstrasse, Germany) 2012 Chae PS, Rasmussen SG, Rana RR, Gotfryd K, Kruse AC, Manglik A, Cho KH, Nurva S, Gether U, Guan L, Loland CJ, Byrne B, Kobilka BK, Gellman SH
• Structure of the δ-opioid receptor bound to naltrindole.
  Nature 2012 Granier S, Manglik A, Kruse AC, Kobilka TS, Thian FS, Weis WI, Kobilka BK
• Crystal structure of the µ-opioid receptor bound to a morphinan antagonist.
  Nature 2012 Manglik A, Kruse AC, Kobilka TS, Thian FS, Mathiesen JM, Sunahara RK, Pardo L, Weis WI, Kobilka BK, Granier S
• Stably integrated luxCDABE for assessment of Salmonella invasion kinetics.
  Molecular imaging 2008 Flentie KN, Qi M, Gammon ST, Razia Y, Lui F, Marpegan L, Manglik A, Piwnica-Worms D, McKinney JS