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Hire Shahid R.

United Kingdom

Senior Scientist, Biophysics & Structural Biology | Translational Drug Discovery | Consultant | Writer

Profile Summary

Experienced life scientist with 15+ years of academic and biotech experience, specializing in membrane protein biophysics, structural biology, and drug discovery. Expert in protein biochemistry, biophysical and structural studies of challenging membrane proteins with a strong publication record and proven translational impact. My research work has founded two biotech spin-outs and advanced drug discovery pipelines in the UK and globally, translating molecular insights into innovative therapeutics.

Subject Matter Expertise

• ★ Biochemistry
• ★ Structural Biology
• ★ Binding Assays
• ☆ Biochemical Assays
• ☆ Enzyme Activity Assays
• ☆ Mutagenesis
• ☆ Recombinant DNA
• ☆ Plasmid DNA
• ☆ Monoclonal Antibody Production
• ☆ Biophysics
• ☆ Biotechnology & Bioengineering
• ☆ Recombinant Protein Expression

Services

• Writing
• Research

Writing Technical Writing

Research User Research, Feasibility Study, Scientific and Technical Research, Secondary Data Collection

Work Experience

Senior Postdoctoral fellow

University of Oxford

February 2026 - Present

Senior Scientist

OMass Therapeutics Ltd

September 2021 - December 2025

University of Helsinki

- December 2021

Postdoctoral fellow

University of Helsinki

September 2016 - August 2021

Education

PhD (Biochemistry)

Oulun Yliopisto

September 2010 - September 2016

M.Phil (Biochemistry)

Quaid-i-Azam University

September 2006 - January 2008

Certifications

• Certification details not provided.

Publications

JOURNAL ARTICLE

Preclinical characterization of novel multi-client inhibitors of Sec61 with broad antitumor activity @article{fd5e51f920714819abaf6972e1663089, title = "Preclinical characterization of novel multi-client inhibitors of Sec61 with broad antitumor activity", abstract = "The Sec61 translocon mediates entry of most secreted and transmembrane proteins into the endoplasmic reticulum, providing a novel therapeutic target to block the expression of protumorigenic factors. Sec61 inhibitors with antitumor activity, mostly derived from natural products, have been reported. However, poor tolerability and suboptimal pharmaceutical properties have precluded their further development. We report here the discovery and characterization of KZR-834 and KZR-261, related small molecule analogs that directly bind to the Sec61 channel to potently inhibit the biogenesis of a subset of Sec61 client proteins. This client inhibition profile includes several tumorigenic factors, results in the activation of an endoplasmic reticulum stress response, and leads to broad anticancer effects in vitro. In vivo, KZR-261 was well tolerated and exhibits antitumor effects across multiple models, both as a single agent and in combination with anti-PD-1 immunotherapy. Based on the strength of this preclinical data, KZR-261 progressed into a phase I clinical trial (NCT05047536) in patients with malignant disease, where it was found to be well tolerated at doses that achieved durable stable disease. These results highlight the potential of Sec61 inhibition as a novel therapeutic target. Significance Statement: KZR-834 and KZR-261 are novel Sec61 inhibitors with the ability to block multiple Sec61 client proteins, leading to well-tolerated efficacy in in vivo cancer models. This represents a novel mechanism for blocking expression of oncogenic factors, including those not amenable to targeting through conventional methods. (c) 2025 The Author(s). Published by Elsevier Inc. on behalf of American Society for Pharmacology and Experimental Therapeutics. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).", keywords = "Anticancer, Drug targets, Oncology, Small molecule, 1182 Biochemistry, cell and molecular biology", author = "Eric Lowe and Anderl, \{Janet L.\} and David Bade and Cristina Delgado-Martin and Chengguo Dong and Fan, \{R. Andrea\} and Ying Fang and Jing Jiang and Johnson, \{Henry W. B.\} and Aaron Kempema and Phil McGilvray and Dustin McMinn and Beatriz Millare and Tony Muchamuel and Nicole Poweleit and Yu Qian and Shahid Rehan and Giovanna Scapin and Ajia Sugahara and Dale Tranter and Brian Tuch and Jinhai Wang and Laurie Wang and Whang, \{Jennifer A.\} and Patricia Zuno-Mitchell and Paavilainen, \{Ville O.\} and Eunyong Park and Jack Taunton and Kirk, \{Christopher J.\} and Anand, \{Neel K.\}", year = "2025", month = aug, doi = "10.1016/j.jpet.2025.103634", language = "English", volume = "392", journal = "Journal of Pharmacology and Experimental Therapeutics", issn = "0022-3565", publisher = "Elsevier Inc. ", number = "8", } . Journal of Pharmacology and Experimental Therapeutics.

Sudeep Karki, Matti Javanainen, Shahid Rehan, Dale Tranter, Juho Kellosalo, Juha T Huiskonen, Lotta Happonen, Ville Paavilainen (2023). Molecular view of ER membrane remodeling by the Sec61/TRAP translocon . EMBO reports.

Molecular view of ER membrane remodeling by the Sec61/TRAP translocon @article{5a590f6596b84a32b4451eb3b55cc250, title = "Molecular view of ER membrane remodeling by the Sec61/TRAP translocon", abstract = "Protein translocation across the endoplasmic reticulum (ER) membrane is an essential step during protein entry into the secretory pathway. The conserved Sec61 protein-conducting channel facilitates polypeptide translocation and coordinates cotranslational polypeptide-processing events. In cells, the majority of Sec61 is stably associated with a heterotetrameric membrane protein complex, the translocon-associated protein complex (TRAP), yet the mechanism by which TRAP assists in polypeptide translocation remains unknown. Here, we present the structure of the core Sec61/TRAP complex bound to a mammalian ribosome by cryogenic electron microscopy (cryo-EM). Ribosome interactions anchor the Sec61/TRAP complex in a conformation that renders the ER membrane locally thinner by significantly curving its lumenal leaflet. We propose that TRAP stabilizes the ribosome exit tunnel to assist nascent polypeptide insertion through Sec61 and provides a ratcheting mechanism into the ER lumen mediated by direct polypeptide interactions.", keywords = "1182 Biochemistry, cell and molecular biology, Structural Biology", author = "Sudeep Karki and Matti Javanainen and Shahid Rehan and Dale Tranter and Juho Kellosalo and Juha Huiskonen and Happonen, \{Lotta J.\} and Ville Paavilainen", year = "2023", month = nov, day = "20", doi = "10.15252/embr.202357910", language = "English", volume = "24", journal = "EMBO Reports", issn = "1469-221X", publisher = "Springer Science and Business Media Deutschland GmbH", } . EMBO Reports.

Signal peptide mimicry primes Sec61 for client-selective inhibition @article{0d54c709ea8d423a8c3067022f4ac6b1, title = "Signal peptide mimicry primes Sec61 for client-selective inhibition", abstract = "Preventing the biogenesis of disease-relevant proteins is an attractive therapeutic strategy, but attempts to target essential protein biogenesis factors have been hampered by excessive toxicity. Here we describe KZR-8445, a cyclic depsipeptide that targets the Sec61 translocon and selectively disrupts secretory and membrane protein biogenesis in a signal peptide-dependent manner. KZR-8445 potently inhibits the secretion of pro-inflammatory cytokines in primary immune cells and is highly efficacious in a mouse model of rheumatoid arthritis. A cryogenic electron microscopy structure reveals that KZR-8445 occupies the fully opened Se61 lateral gate and blocks access to the lumenal plug domain. KZR-8445 binding stabilizes the lateral gate helices in a manner that traps select signal peptides in the Sec61 channel and prevents their movement into the lipid bilayer. Our results establish a framework for the structure-guided discovery of novel therapeutics that selectively modulate Sec61-mediated protein biogenesis.", keywords = "Passive membrane-permeability, Linear constraint solver, General force-field, Particle mesh ewald, Endoplasmic-reticulum, Protein translocation, Cotranslational translocation, Microsomal-membranes, Lipid-composition, Structural basis, 1182 Biochemistry, cell and molecular biology", author = "Shahid Rehan and Dale Tranter and Sharp, \{Phillip P. P.\} and Craven, \{Gregory B. B.\} and Eric Lowe and Anderl, \{Janet L. L.\} and Tony Muchamuel and Vahid Abrishami and Suvi Kuivanen and Wenzell, \{Nicole A. A.\} and Andy Jennings and Chakrapani Kalyanaraman and Tomas Strandin and Matti Javanainen and Olli Vapalahti and Jacobson, \{Matthew P. P.\} and Dustin McMinn and Kirk, \{Christopher J.\} and Huiskonen, \{Juha T.\} and Jack Taunton and Paavilainen, \{Ville O.\}", year = "2023", doi = "10.1038/s41589-023-01326-1", language = "English", volume = "19", pages = "1054–1062", journal = "Nature Chemical Biology", issn = "1552-4450", publisher = "Nature Research ", } . Nature Chemical Biology.

(2020). Pendant-bearing glucose-neopentyl glycol (P-GNG) amphiphiles for membrane protein manipulation: Importance of detergent pendant chain for protein stabilization . Acta Biomaterialia.

Pendant-bearing glucose-neopentyl glycol (P-GNG) amphiphiles for membrane protein manipulation @article{5a2a1fddb8d144488f1809ea9cc54138, title = "Pendant-bearing glucose-neopentyl glycol (P-GNG) amphiphiles for membrane protein manipulation: Importance of detergent pendant chain for protein stabilization", abstract = "Glucoside detergents are successfully used for membrane protein crystallization mainly because of their ability to form small protein-detergent complexes. In a previous study, we introduced glucose neopentyl glycol (GNG) amphiphiles with a branched diglucoside structure that has facilitated high resolution crystallographic structure determination of several membrane proteins. Like other glucoside detergents, however, these GNGs were less successful than DDM in stabilizing membrane proteins, limiting their wide use in protein structural study. As a strategy to improve GNG efficacy for protein stabilization, we introduced two different alkyl chains (i.e., main and pendant chains) into the GNG scaffold while maintaining the branched diglucoside head group. Of these pendant-bearing GNGs (P-GNGs), three detergents (GNG-2,14, GNG-3,13 and GNG-3,14) were not only notably better than both DDM (a gold standard detergent) and the previously described GNGs at stabilizing all six membrane proteins tested here, but were also as efficient as DDM at membrane protein extraction. The results suggest that the C14 main chain of the P-GNGs is highly compatible with the hydrophobic widths of membrane proteins, while the C2/C3 pendant chain is effective at strengthening detergent hydrophobic interactions. Based on the marked effect on protein stability and solubility, these glucoside detergents hold significant potential for membrane protein structural study. Furthermore, the independent roles of the detergent two alkyl chains first introduced in this study have shed light on new amphiphile design for membrane protein study.Statement of significanceDetergent efficacy for protein stabilization tends to be protein-specific, thus it is challenging to find a detergent that is effective at stabilizing multiple membrane proteins. By incorporating a pendant chain into our previous GNG scaffold, we prepared pendant chain-bearing GNGs (P-GNGs) and identified three P-GNGs that were highly effective at stabilizing all membrane proteins tested here including two GPCRs. In addition, the new detergents were as efficient as DDM at extracting membrane proteins, enabling use of these detergents over the multiple steps of protein isolation. The key difference between the P-GNGs and other glucoside detergents, the presence of a pendant chain, is likely to be responsible for their markedly enhanced protein stabilization behavior. (c) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.", keywords = "Amphiphiles, Membrane proteins, Protein stabilization, Amphiphile design, Protein structure, EQUILIBRATIVE NUCLEOSIDE TRANSPORTER-1, MALEIC ACID COPOLYMER, CRYSTAL-STRUCTURE, BETA(2)-ADRENERGIC RECEPTOR, ALLOSTERIC MODULATION, MELIBIOSE PERMEASE, ESCHERICHIA-COLI, HENT1 PROTEIN, PURIFICATION, STABILITY, 1182 Biochemistry, cell and molecular biology", author = "Bae, \{Hyoung Eun\} and Cristina Cecchetti and Yang Du and Satoshi Katsube and Mortensen, \{Jonas S.\} and Weijiao Huang and Shahid Rehan and Lee, \{Ho Jin\} and Loland, \{Claus J.\} and Lan Guan and Kobilka, \{Brian K.\} and Bernadette Byrne and Chae, \{Pil Seok\}", year = "2020", month = aug, doi = "10.1016/j.actbio.2020.06.001", language = "English", volume = "112", pages = "250--261", journal = "Acta Biomaterialia", issn = "1742-7061", publisher = "Acta Materialia Inc", } . Acta Biomaterialia.

Current Progress on Equilibrative Nucleoside Transporter Function and Inhibitor Design <head> <META HTTP-EQUIV="Refresh" CONTENT="0;URL=/servlet/useragent"> </head> . SLAS Discovery.

Current Progress on Equilibrative Nucleoside Transporter Function and Inhibitor Design @article{a3ce9666ab594c5594c25c303a30175e, title = "Current Progress on Equilibrative Nucleoside Transporter Function and Inhibitor Design", abstract = "Physiological nucleosides are used for the synthesis of DNA, RNA, and ATP in the cell and serve as universal mammalian signaling molecules that regulate physiological processes such as vasodilation and platelet aggregation by engaging with cell surface receptors. The same pathways that allow uptake of physiological nucleosides mediate the cellular import of synthetic nucleoside analogs used against cancer, HIV, and other viral diseases. Physiological nucleosides and nucleoside drugs are imported by two families of nucleoside transporters: the SLC28 concentrative nucleoside transporters (CNTs) and SLC29 equilibrative nucleoside transporters (ENTs). The four human ENT paralogs are expressed in distinct tissues, localize to different subcellular sites, and transport a variety of different molecules. Here we provide an overview of the known structure-function relationships of the ENT family with a focus on ligand binding and transport in the context of a new hENT1 homology model. We provide a generic residue numbering system for the different ENTs to facilitate the interpretation of mutational data produced using different ENT homologs. The discovery of paralog-selective small-molecule modulators is highly relevant for the design of new therapies and for uncovering the functions of poorly characterized ENT family members. Here, we discuss recent developments in the discovery of new paralog-selective small-molecule ENT inhibitors, including new natural product-inspired compounds. Recent progress in the ability to heterologously produce functional ENTs will allow us to gain insight into the structure and functions of different ENT family members as well as the rational discovery of highly selective inhibitors.", keywords = "nucleoside, membrane transporter, equilibrative nucleoside transporter (ENT), cancer, structural biology, PROTEIN-STRUCTURE, S-6-(4-NITROBENZYL)-MERCAPTOPURINE RIBOSIDE, MOLECULAR CHARACTERIZATION, NUCLEOBASE TRANSPORT, CHIMERIC CONSTRUCTS, RECOMBINANT HUMAN, ANALOGS, MUTATION, FAMILY, HENT1, 116 Chemical sciences, 1182 Biochemistry, cell and molecular biology, 1183 Plant biology, microbiology, virology", author = "Shahid Rehan and Saman Shahid and Salminen, \{Tiina A.\} and Veli-Pekka Jaakola and Paavilainen, \{Ville O.\}", year = "2019", month = dec, doi = "10.1177/2472555219870123", language = "English", volume = "24", pages = "953--968", journal = "SLAS discovery ", issn = "2472-5552", publisher = "Society for Laboratory Automation and Screening (SLAS)", number = "10", } . SLAS discovery.

(2019). Current Progress on Equilibrative Nucleoside Transporter Function and Inhibitor Design . SLAS DISCOVERY: Advancing Life Sciences R&D.

Rapamycin-inspired macrocycles with new target specificity @article{0d249a2eec11482e9879d0b26e1780b4, title = "Rapamycin-inspired macrocycles with new target specificity", abstract = "Rapamycin and FK506 are macrocyclic natural products with an extraordinary mode of action, in which they form binary complexes with FK506-binding protein (FKBP) through a shared FKBP-binding domain before forming ternary complexes with their respective targets, mechanistic target of rapamycin (mTOR) and calcineurin, respectively. Inspired by this, we sought to build a rapamycin-like macromolecule library to target new cellular proteins by replacing the effector domain of rapamycin with a combinatorial library of oligopeptides. We developed a robust macrocyclization method using ring-closing metathesis and synthesized a 45,000-compound library of hybrid macrocycles (named rapafucins) using optimized FKBP-binding domains. Screening of the rapafucin library in human cells led to the discovery of rapadocin, an inhibitor of nucleoside uptake. Rapadocin is a potent, isoform-specific and FKBP-dependent inhibitor of the equilibrative nucleoside transporter 1 and is efficacious in an animal model of kidney ischaemia reperfusion injury. Together, these results demonstrate that rapafucins are a new class of chemical probes and drug leads that can expand the repertoire of protein targets well beyond mTOR and calcineurin.", keywords = "116 Chemical sciences, EQUILIBRATIVE NUCLEOSIDE TRANSPORTER, ISCHEMIA-REPERFUSION INJURY, FUNCTIONAL-CHARACTERIZATION, ADENOSINE RECEPTORS, IMMUNOSUPPRESSANT FK506, CYCLOSPORINE-A, HIGH-AFFINITY, BINDING, PROTEIN, CALCINEURIN", author = "Zufeng Guo and Hong, \{Sam Y.\} and Jingxin Wang and Shahid Rehan and Wukun Liu and Hanjing Peng and Manisha Das and Wei Li and Shridhar Bhat and Brandon Peiffer and Ullman, \{Brett R.\} and Chung-Ming Tse and Zlatina Tarmakova and Cordelia Schiene-Fischer and Gunter Fischer and Imogen Coe and Paavilainen, \{Ville O.\} and Zhaoli Sun and Liu, \{Jun O.\}", year = "2019", month = mar, doi = "10.1038/s41557-018-0187-4", language = "English", volume = "11", pages = "254--263", journal = "Nature Chemistry", issn = "1755-4349", publisher = "Nature Publishing Group", number = "3", } . Nature Chemistry.

Functional reconstitution of human equilibrative nucleoside transporter-1 into styrene maleic acid co-polymer lipid particles @article{a729b6bef395409995238b40cadc3e4c, title = "Functional reconstitution of human equilibrative nucleoside transporter-1 into styrene maleic acid co-polymer lipid particles", abstract = "The human equilibrative nucleoside transporter-1 (hENT1) is important for the entry of anti-cancer and antiviral nucleoside analog therapeutics into the cell, and thus for their efficacy. Understanding of hENT1 structure -function relationship could assist with development of nucleoside analogs with better cellular uptake properties. However, structural and biophysical studies of hENT1 remain challenging as the hydrophobic nature of the protein leads to complete aggregation upon detergent-based membrane isolation. Here we report detergent-free reconstitution of the hENT1 transporter into styrene maleic acid co-polymer lipid particles (SMALPs) that form a native lipid disc. SMALP-purified hENT1, expressed in Sf9 insect cells binds a variety of ligands with a similar affinity as the protein in native membrane, and exhibits increased thermal stability compared to detergent-solubilized hENT1. hENT1-SMALPs purified using FLAG affinity M2 resin yielded similar to 0.4 mg of active and homogenous protein per liter of culture as demonstrated by ligand binding, size-exclusion chromatography and SDS-PAGE analyses. Electrospray ionization mass spectrometry (ESI-MS) analysis showed that each hENT1 lipid disc contains 16 phosphatidylcholine (PC) and 2 phosphatidylethanolamine (PE) lipid molecules. Polyunsaturated lipids are specifically excluded from the hENT1 lipid discs, possibly reflecting a functional requirement for a dynamic lipid environment. Our work demonstrates that human nucleoside transporters can be extracted and purified without removal from their native lipid environment, opening up a wide range of possibilities for their biophysical and structural studies. (C) 2017 Elsevier B.V. All rights reserved.", keywords = "Membrane proteins, Lipid, Model membrane, Nucleoside transporter, SMALPs, INTEGRAL MEMBRANE-PROTEINS, MASS-SPECTROMETRY, FREE PURIFICATION, INSECT CELLS, CRYO-EM, BINDING, ENVIRONMENT, INHIBITION, RECEPTORS, COMPLEXES, 1182 Biochemistry, cell and molecular biology", author = "Shahid Rehan and Paavilainen, \{Ville O.\} and Veli-Pekka Jaakola", year = "2017", month = may, doi = "10.1016/j.bbamem.2017.02.017", language = "English", volume = "1859", pages = "1059--1065", journal = "Biochimica et Biophysica Acta. Biomembranes", issn = "0005-2736", publisher = "Elsevier B.V.", number = "5", } . Biochimica et Biophysica Acta. Biomembranes.

Rehan, S., Paavilainen, V.O., Jaakola, V.-P.(2017). Functional reconstitution of human equilibrative nucleoside transporter-1 into styrene maleic acid co-polymer lipid particles . Biochimica et Biophysica Acta - Biomembranes. 1859. (5). Microsoft.AspNetCore.Mvc.Localization.LocalizedHtmlString 1059-1065.

Thermodynamics and kinetics of inhibitor binding to human equilibrative nucleoside transporter subtype-1. @article{ee3d8b28a26c4a999cf021280d443d13, title = "Thermodynamics and kinetics of inhibitor binding to human equilibrative nucleoside transporter subtype-1.", keywords = "317 Pharmacy", author = "Shahid Rehan and Yash Ashok and Rahul Nanekar and Veli-Pekka Jaakola", year = "2015", month = dec, doi = "10.1016/j.bcp.2015.09.019", language = "English", volume = "98", pages = "681--689", journal = "Biochemical Pharmacology", issn = "0006-2952", publisher = "Elsevier Inc. ", number = "4", } . Biochemical Pharmacology.

Expression, purification and functional characterization of human equilibrative nucleoside transporter subtype-1 (hENT1) protein from Sf9 insect cells @article{b79a48315d9f48399347d538758f9981, title = "Expression, purification and functional characterization of human equilibrative nucleoside transporter subtype-1 (hENT1) protein from Sf9 insect cells", keywords = "1182 Biochemistry, cell and molecular biology", author = "Shahid Rehan and Veli-Pekka Jaakola", year = "2015", month = oct, doi = "10.1016/j.pep.2015.07.003", language = "English", volume = "114", pages = "99", journal = "Protein Expression and Purification", issn = "1046-5928", publisher = "Academic Press Inc.", } . Protein Expression and Purification.

Rehan, S., Ashok, Y., Nanekar, R., Jaakola, V.-P.(2015). Thermodynamics and kinetics of inhibitor binding to human equilibrative nucleoside transporter subtype-1 . Biochemical Pharmacology. 98. (4). Microsoft.AspNetCore.Mvc.Localization.LocalizedHtmlString 681-689.

Rehan, S., Jaakola, V.-P.(2015). Expression, purification and functional characterization of human equilibrative nucleoside transporter subtype-1 (hENT1) protein from Sf9 insect cells . Protein Expression and Purification. 114. Microsoft.AspNetCore.Mvc.Localization.LocalizedHtmlString 99-107.