Summary
Overview
Work History
Education
Skills
Accomplishments
Published Work
Timeline
Generic

Pankaj Panwar

Surrey, Canada,BC

Summary

Collaborative structural biologist with 15 years of experience in producing membrane proteins (GPCRs, ion channels, transporters, Intramembrane proteases) and soluble proteins (Fabs, disulfide rich, intrinsically disordered and multiprotein complexes) by employing bacterial, mammalian and insect expression systems.

Overview

15
15
years of professional experience

Work History

Senior Scientist

AbCellera Biologics Inc.
Vancouver, BC
01.2022 - 11.2023
  • Designed constructs for targeted recombinant protein production for multiple targets, adeptly addressed expression and stability limitations using advanced protein design approaches. Notably Stabilized an exceptionally challenging viral protein prefusion conformation by introducing non-native cysteines (Schrödinger BioLuminate and AF2)
  • Expressed recombinant proteins using mammalian (HEK293 & CHO) and insect (SF9 & Hi5) cell hosts from small-scale to large-scale level, and delivered milligram quantities of low-expressing ion-channel and GPCR targets
  • Efficiently managed installation and operation of TalosL120C EM, computational infrastructure, and sample preparation facilities, ensuring rapid delivery of structural data (typically 1-4 weeks for all protein classes)
  • Built a network of 5 CryoEM CROs to enable cost-effective and scalable CryoEM access
  • Delivered 43 high resolution structures and 16 low resolution models across 10 distinct antigen-antibody targets
  • Improved average resolution from 5-3.5 Å (2021) to 4-2.7 Å (2023)
  • Integrated novel methods for resolution and angular distribution improvement for small MW targets and successfully determined 5 distinct structures in ~50-80 Kda MW range
  • Creatively employed protein engineering and cross-linking to characterize low affinity complexes, successfully determining structures for a lead series with high off rates
  • Designed in-silico mutations and combinatorial libraries using physics (Schrödinger BioLuminate) and ML (GNN models) based tools and successfully improved lead affinities for 2 distinct GPCR antagonist discovery projects
  • Developed protocols for VLP generation for GPCR targets and explored customizable nanoparticle designs for membrane protein targets
  • Realized innovative strategies for epitope coverage enhancement that resulted in discovery of diverse antibody leads for a target with a single dominant epitope

Research Scientist

AbCellera Biologics Inc.
Vancouver, BC
08.2020 - 12.2021
  • Designed constructs for targeted recombinant protein production for multiple targets, adeptly addressed expression and stability limitations using advanced protein design approaches. Notably Stabilized exceptionally challenging viral protein prefusion conformation by introducing non-native cysteines (Schrödinger BioLuminate and AF2)
  • Expressed recombinant proteins using mammalian (HEK293 & CHO) and insect (SF9 & Hi5) cell hosts from small-scale to large-scale level, and delivered milligram quantities of low-expressing ion-channel and GPCR targets
  • Efficiently managed installation and operation of TalosL120C EM, computational infrastructure, and sample preparation facilities, ensuring rapid delivery of structural data (typically 1-4 weeks for all protein classes)
  • Built a network of 5 CryoEM CROs to enable cost-effective and scalable CryoEM access
  • Delivered 43 high resolution structures and 16 low resolution models across 10 distinct antigen-antibody targets
  • Improved average resolution from 5-3.5 Å (2021) to 4-2.7 Å (2023)
  • Integrated novel methods for resolution and angular distribution improvement for small MW targets and successfully determined 5 distinct structures in ~50-80 Kda MW range
  • Creatively employed protein engineering and cross-linking to characterize low affinity complexes, successfully determining structures for a lead series with high off rates
  • Designed in-silico mutations and combinatorial libraries using physics (Schrödinger BioLuminate) and ML (GNN models) based tools and successfully improved lead affinities for 2 distinct GPCR antagonist discovery projects
  • Developed protocols for VLP generation for GPCR targets and explored customizable nanoparticle designs for membrane protein targets
  • Realized innovative strategies for epitope coverage enhancement that resulted in discovery of diverse antibody leads for a target with a single dominant epitope

Research Associate

University Of British Columbia
Vancouver, BC
07.2019 - 07.2020
  • Developed an efficient protocol for isolation of voltage gated calcium channel and determine 3D structures of the channel in complex with an interacting partner
  • Combined molecular modeling and electrocardiographic recordings to gain mechanistic insight into the genetic culprits of Type-8 long QT syndrome [EP Europace, 2019]
  • Designed stable constructs for an intrinsically disordered protein and revealed substrate recognition mechanism by structural and functional characterization [PNAS, 2022]
  • Proposed successful strategies for an ABC transporter stabilization and assisted in structure determination [Nature communications, 2021]

Postdoctoral Fellow

University Of British Columbia
Vancouver, BC
07.2014 - 06.2019
  • Developed an efficient protocol for isolation of voltage gated calcium channel and determine 3D structures of the channel in complex with an interacting partner
  • Combined molecular modeling and electrocardiographic recordings to gain mechanistic insight into the genetic culprits of Type-8 long QT syndrome [EP Europace, 2019]
  • Designed stable constructs for an intrinsically disordered protein and revealed substrate recognition mechanism by structural and functional characterization [PNAS, 2022]
  • Proposed successful strategies for an ABC transporter stabilization and assisted in structure determination [Nature communications, 2021]

CIHR-THRUST Postdoctoral Fellow

University Of Alberta
Vancouver, BC
04.2012 - 06.2014
  • Uncovered refolding mechanism for two distinct intramembrane proteases and provided key insight into their structure-activity relationships [Biophysical journal 2016]
  • Combined homology modeling and molecular docking and deciphered substrate specificity mechanisms for a glucose transporter and plant based nucleotide transporter [JBC, 2015; PLOS ONE 2014]
  • Developed a FRET based kinetic assay to probe the catalytic properties of a serine protease and deduced novel mechanism of substrate specific cleavage [EMBO, 2014]

IRTELIS Predoctoral Fellow

University Of Grenoble
Vancouver, BC
10.2008 - 01.2012
  • Identified small-molecule inhibitors against a transporter using virtual screening of a chemical library (~10M compounds) utilizing Schrödinger Glide
  • Characterized a plant nucleotide transporter and uncovered novel insights into substrate transport mechanism [PLOS ONE, 2012]

Education

Ph.D. - Structural Biology

Institut De Biologie Structurale
Grenoble, France
2012

Master of Science - Biotechnology

Indian Institute of Technology
Roorkee, India
2008

Skills

  • Protein and antibody purification: Affinity, IEX, SEC, HIC, MMC using FPLC system
  • Analytical characterization: DSC, DSF, FT-IR, SEC-MALS, DLS, MP and CD
  • Binding validation and characterization using ITC, MST, BLI, ELISA and nsEM
  • Automation system (Hamilton microlab)
  • CryoEM, X-ray diffraction, molecular modeling and docking to guide hit identification, lead optimization, and development of SBDD strategies
  • AF2, Schrödinger BioLuminate, RFdiffusion and ProteinMPNN
  • Optimizing lead antibodies to attain desired levels of affinity and developability profile
  • Data organization using Benchling and electronic lab notebooks

Accomplishments

  • Spearheaded the formation of a 5 member structural biology team from ground up and developed a highly efficient and cost effective gene-to-structure CryoEM pipeline
  • Team lead responsible for structural characterization of Covid-19 therapeutic antibodies in collaboration with Eli Lilly and DARPA [Cell Reports, 2022]
  • Regularly presented research findings to external and internal collaborators, and non-scientific audience
  • Contributed to the preparation of data packages for scientific publications, IND filing and patent applications
  • Outstanding leadership qualities exhibited through the provision of effective mentorship to team members: Post-docs (4), PhDs (1), undergraduates (6)
  • Experience in interfacing with cross-functional teams including AI/ML scientists, Conjugation chemists, and cellular biologists to drive integrated drug discovery projects

Published Work

  • Westendorf K, Žentelis S, Wang L, Foster D, Vaillancourt P, Wiggin M, Lovett E, Lee R, Hendle J, Pustilnik A, Sauder JM, Kraft L, Hwang Y, Siegel RW, Chen J, Heinz BA, Higgs RE, Kallewaard NL, Jepson K, Goya R, Smith MA, Collins DA, Pellacani D, Xiang P, Puyraimond VD, Ricicova M, Devorkin L, Pritchard C, Dalal K, Panwar P, Dhupar H, Garces FA, Cohen CA, Dye JM, Huie K, Badger CV, Kobasa D, Audet J, Freitas JJ, Hassanali S, Hughes I, Munoz L, Palma HC, Ramamurthy B, Cross RW, Geisbert TW, Menachery V, Lokugamage K, Borisevich V, Lanz I, Anderson L, Sipahimalani P , Corbett KS, Yang EY, Zhang Y, Shi W, Zhou Y, Choe M, Misasi J, Kwong PD, Sullivan NJ, Graham BS, Fernandez TL, Hansen CL, Falconer E, Mascola JR, Jones BE, Barnhart BC (2022). LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV2 variants. Cell Reports 39(7)
  • Safabakhsh S, Panwar P, Barichello S, Sangha SS, Hanson PJ, Petegem FV, Laksman Z (2022). The role of phosphorylation in atrial fibrillation: a focus on mass spectrometry approaches. Cardiovascular Research 118(5):1205-1217
  • Zheng FY, Panwar P*, McFarlane CR, Tuinte WE, Campiglio M, Petegem FV (2022). Structures of the junctophilin/voltage-gated calcium channel interface reveal hot spot for cardiomyopathy mutations. Proceedings of the National Academy of Sciences 119(10): e2120416119
  • Scortecci JF, Molday LJ, Curtis SB, Garces FA, Panwar P, Petegem FV, Molday RS (2021). Cryo-EM structures of the ABCA4 importer reveal mechanisms underlying substrate binding and Stargardt disease. Nature communications 12(1):5902
  • Asghari P, Scriven RDL, Ng M, Panwar P, Chou KC, Petegem FV, Moore EDW (2020). Cardiac ryanodine receptor distribution is dynamic and changed by auxiliary proteins and post-translational modification. Elife 9:e51602
  • Mellor GJ, Pankaj Panwar*, Lee AK, Steinberg C, Hathaway JA, Bartels K, Christian S, Balaji S, Roberts JD, Simpson CS, Boczek NJ, Tester DJ, Radbill AE, Mok NE, Hamilton RM, Kaufman ES, Eugenio PJ, Weiss R, January C, McDaniel GM, Leather GA, Erickson C, Falik S, Behr E, Wilde AM, Sanatani S, Ackerman MJ, Petegem FV, Krahn AD, Laksman Z (2019). Type 8 long QT syndrome: pathogenic variants in CACNA1C-encoded Cav1.2 cluster in STAC protein binding site. Ep Europace 21(11):1725-1732
  • Long W, Pangrahi R, Panwar P, Chen XZ, Lemieux MJ, Cheeseman CI (2017). Mechanism and the structural basis of urate/fructose exchange in Human Glucose Transporter 9 (hSLC2A9). Scientific Reports 7: 41167
  • Panigrahi R, Arutyunova E, Panwar P, Gimpl K, Keller S, Lemieux MJ (2016). Reversible unfolding of rhomboid intramembrane proteases. Biophysical Journal 110(6):1379-1390
  • Long W, Panwar P, Witkowska K, Wong K, O'Neill D, Chen X, Lemieux MJ, Cheeseman CI (2015). Critical Roles of two hydrophobic residues within human glucose transporter 9 (hSLC2A9) in substrate selectivity and urate transport. The Journal of Biological Chemistry. 290(24):15292-303
  • Witz S, Panwar P, Schober M, Deppe J, Pasha FA, Lemieux MJ, Möhlmann T (2014). Structure-function relationship of a plant NCS1 memberhomology modeling and mutagenesis identified residues critical for substrate specificity of PLUTO, a nucleobase transporter from Arabidopsis. PLOS one. 9(3): e91343
  • Arutyunova E*, Panwar P*, Skiba PM, Gale N, Mak MW, Lemieux MJ (2014). Allosteric regulation of rhomboid intramembrane proteolysis. EMBO Journal. 33(17): 1869-1881
  • Panwar P*, Lemieux MJ (2014). Expression and Purification of Haemophilus influenzae Rhomboid Intramembrane Protease GlpG for Structural Studies. Current Protocols in Protein Science 76(1):29.9.1-29.9.25
  • Panwar P, Deniaud A, Pebay-Peyroula E (2012). Contamination from an affinity column: an encounter with a new villain in the world of membrane-protein crystallization. Acta Crystallographica D - Biological Crystallography. 68(10): 1272-1277
  • Deniaud A, Panwar P, Barrand AF, Bernaudat F, Juillan-Binard C, Ebel C, Rolland N, Pebay-Peyroula E (2012). Oligomeric status and nucleotide binding properties of the plastid ATP/ADP transporter 1: toward a molecular understanding of the transport mechanism. PLOS one. 7(3):e32325


Joint first-author*

Timeline

Senior Scientist

AbCellera Biologics Inc.
01.2022 - 11.2023

Research Scientist

AbCellera Biologics Inc.
08.2020 - 12.2021

Research Associate

University Of British Columbia
07.2019 - 07.2020

Postdoctoral Fellow

University Of British Columbia
07.2014 - 06.2019

CIHR-THRUST Postdoctoral Fellow

University Of Alberta
04.2012 - 06.2014

IRTELIS Predoctoral Fellow

University Of Grenoble
10.2008 - 01.2012

Ph.D. - Structural Biology

Institut De Biologie Structurale

Master of Science - Biotechnology

Indian Institute of Technology
Pankaj Panwar