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S. Saif Hasan, PhD

Academic Title:

Assistant Professor

Primary Appointment:

Biochemistry and Molecular Biology

Additional Title:

Group Leader, CBT and IBBR

Email:

sshasan@som.umaryland.edu

Location:

Rockville MD

Phone (Primary):

240-314-6396

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Education and Training

  • B.Sc., Biochemistry, Aligarh Muslim University, India, 2004
  • M.Sc., Biotechnology, University of Pune, India, 2006
  • Ph.D., Biological Sciences, Purdue University, USA, 2013
  • Postdoctoral Research, Purdue University, USA, 2019

Biosketch

My doctoral research on the structure-function studies of the hetero-oligomeric cytochrome b6f complex of the photosynthetic membranes has given me experience in genetic modification, expression, purification, crystallization, and structure determination of membrane protein complexes.

As a post-doctoral researcher, I investigated the structural basis of interactions of membrane-containing flaviviruses and alphaviruses with neutralizing antibodies, thus expanding my research expertise to cryo-electron microscopy, while utilizing my experience in membrane protein biochemistry and structural biology.

As an independent investigator at the University of Maryland, my group investigates the structural basis of viral protein trafficking between cellular organelles. Our research provides insights into virus progeny assembly and the export of genetic vaccines to the cell surface for immune presentation. 

My laboratory is located in the Center for Biomolecular Therapeutics (CBT) in Rockville, MD (address below)

Center for Biomolecular Therapeutics (CBT)

Institute for Bioscience and Biotechnology Research (IBBR)

9600 Gudelsky Drive

Rockville, MD 20850

Research/Clinical Keywords

Cryo-Electron Microscopy, Infectious Viruses, Inter-Organelle Trafficking, Membrane Proteins, Protein Secretion, Structural Biology, Vesicular Trafficking, Viral Structures, X-Ray Crystallography

Highlighted Publications

Representative publications from graduate and post-doctoral research:

Hasan SS, Yamashita E, Baniulis D, Cramer WA. Quinone-dependent proton transfer pathways in the photosynthetic cytochrome b6f Proc Natl Acad Sci U S A. 2013;110(11):4297-302. PubMed PMID: 23440205; PubMed Central PMCID: PMC3600468.

Hasan SS, Miller A, Sapparapu G, Fernandez E, Klose T, Long F, Fokine A, Porta JC, Jiang W, Diamond MS, Crowe JE Jr, Kuhn RJ, Rossmann MG. A human antibody against Zika virus crosslinks the E protein to prevent infection. Nat Commun. 2017;8:14722. PubMed PMID: 28300075; PubMed Central PMCID: PMC5356071.

Hasan SS, Sun C, Kim AS, Watanabe Y, Chen CL, Klose T, Buda G, Crispin M, Diamond MS, Klimstra WB, Rossmann MG. Cryo-EM structures of Eastern Equine Encephalitis Virus reveal mechanisms of virus disassembly and antibody neutralization. Cell Rep. 2018;25(11):3136-3147. PubMed PMID: 30540945; PubMed Central PMCID: PMC6302666

Hasan SS, Sevvana M, Kuhn RJ, Rossmann MG. Structural biology of Zika virus and other flaviviruses. Nat Struct Mol Biol. 2018;25(1):13-20. PubMed PMID: 29323278 (review article)

Dey D, Qing E, He Y, Chen Y, Jennings B, Cohn W, Singh S, Gakhar L, Schnicker NJ, Pierce BG, Whitelegge JP, Doray B, Orban J, Gallagher T, Hasan SS. A single C-terminal residue controls SARS-CoV-2 spike trafficking and incorporation into VLPs. Nat Commun. 2023 Dec 15;14(1):8358. doi: 10.1038/s41467-023-44076-3. PMID: 38102143; PMCID: PMC10724246.

Mishra AK, Shahid S, Karade SS, Agnihotri P, Kolesnikov A, Hasan SS, Mariuzza RA. CryoEM structure of a therapeutic antibody (favezelimab) bound to human LAG3 determined using a bivalent Fab as fiducial marker. Structure. 2023 Oct 5;31(10):1149-1157.e3. doi: 10.1016/j.str.2023.07.013. Epub 2023 Aug 23. PMID: 37619561.

Dey D, Hasan SS. Strategies for rapid production of crystallization quality coatomer WD40 domains. Protein Expr Purif. 2023 Dec;212:106358. doi: 10.1016/j.pep.2023.106358. Epub 2023 Aug 23. PMID: 37625737; PMCID: PMC10529451.

Complete List of Publications:

Research Interests

Our research focuses on one fundamental question: how does inter-organelle trafficking of proteins take place from the atomic to the cellular level? To address this question, we employ the coronavirus spike protein as our favorite tool and we have two major research directions: 

(I) Evolution of coronavirus protein trafficking: The newly synthesized coronavirus proteins traverse organelles and membranes to travel to the progeny assembly site in ER-Golgi intermediate compartment. Coronavirus proteins travel within the infected cells by co-opting and repurposing existing cellular highways and signals that evolved to transport cellular cargo between organelles. We investigate the atomic-level mechanisms by which coronaviruses co-opt these cellular highways and how viral trafficking strategies evolve in the face of selection pressure from the host trafficking machinery and competition from endogenous clients. The overarching goal is to use this fundamental information to develop small molecule therapeutics that disrupt coronavirus protein trafficking, and thus inhibit propagation of coronavirus infections. 

(II) Intra-cellular trafficking of coronavirus genetic vaccines: The COVID-19 pandemic brought spike genetic vaccines from bench to bedside in a remarkably short period of time. The success of these vaccines depends on the correct biosynthesis of the spike protein and export to the cell surface where they are displayed to the immune system. We investigate the atomic basis of this trafficking, and the myriad of structural transitions that the spike protein undergoes in its journey from the inside of cells to the cell surface. Our overarching goal is to determine how genetic differences in the trafficking machinery in distinct human populations control the biogenesis and export of the spike protein and to use this fundamental information to improve the immunogenicity of spike-based genetic vaccines. 

Awards and Affiliations

  • 2003 & 2004 : ‘JNCASR – Summer Research Fellowship’ awarded by the Jawaharlal Nehru Centre for Advanced Scientific Research (Bangalore), Rajiv Gandhi Foundation (New Delhi) and Department of Science and Technology (Government of India).
  • 2005: University Medal for highest marks in Bachelor of Science (Honors) Biochemistry awarded by the Aligarh Muslim University, Aligarh (India).
  • 2005: University Medal for highest marks in the Faculty of Life Sciences awarded by the Aligarh Muslim University, Aligarh (India).
  • 2005: Nationally competed scholarship for higher studies awarded by the Bharat Petroleum Corporation Limited (India).
  • 2011: Best talk by a graduate student (co-winner) at the 37th Midwest-Southeast Photosynthesis Meeting, Marshall IN (USA).
  • 2012: Student Research Achievement Award at the 56th Annual Biophysical Society Meeting, San Diego CA (USA).
  • 2018: Best talk by a post-doctoral researcher at The Hitchhiker’s Guide to the Biomolecular Galaxy: A Purdue Mini-symposium on Integrating Structure, Function, and Interactions of the Biomolecular Universe at Purdue University, West Lafayette IN, USA
  • 2018: Best short talk by a post-doctoral researcher at the Third Annual Life Sciences Postdoc Symposium at Purdue University, West Lafayette IN, USA
  • 2019: Biophysical Society travel award to present research at the 63rd Annual Biophysical Society Meeting, Baltimore MD (USA)
  • 2022: Pre-Clerkship Teaching commendation award from the University of Maryland School of Medicine, Baltimore MD (USA)
  • 2023: Pre-Clerkship Teaching commendation award from the University of Maryland School of Medicine, Baltimore MD (USA)
  • 2024: Teaching of the Year, GPILS, University of Maryland Baltimore MD (USA)

Grants and Contracts

  • 2019-20: Principal Investigator (multi-investigator), “Molecular Architecture of KDELR-Gq, an Oncogenic Trans-Membrane Signaling Complex”, University of Maryland MPower
  • 2020-21: Principal Investigator (multi-investigator), “Structural Investigations of KDEL Receptors”, University of Maryland MPower
  • 2020-21: Principal Investigator (multi-investigator), “Molecular Investigations of SARS-CoV-2 Spike Protein”, UMaryland MPower COVID19 Response Fund Award
  • 2021-22: Principal Investigator, “Molecular Lipidomics of a Therapeutic Target in Coronavirus Assembly”, American Thoracic Society/GlaxoSmithKline   
  • 2021-22: Principal Investigator, “Molecular Investigations of KDEL Receptor Retrograde Trafficking and its Viral Hijacking”, University of Maryland MPower
  • 2023-24: Principal Investigator, “Structural Investigation of SARS-CoV-2 Spike Protein”, American Thoracic Society
  • 2023-2028: Principal Investigator, "Biophysical, Structural, and Cellular Dissection of COPI-Dependent Retrograde Trafficking Using a Coronavirus Toolkit", NIH/NIGMS R01
  • 2024-2026: Principal Investigator, "Structural Investigations of Coronavirus Spike Protein", NIH/NIAID R21

Professional Activity

  • 2019: Ad-hoc reviewer, Biotechnology and Biological Sciences Research Council, United Kingdom
  • 2022: Ad-hoc early career reviewer, Biochemistry and Biophysics of Membranes Study Section, NIH (June 2022 Council Meeting)
  • 2022: Ad-hoc reviewer, Medical Research Council, United Kingdom
  • 2023: Ad-hoc reviewer, Macromolecular Structure and Function C Study Section, NIH (June 2023 Council Meeting)
  • 2023: Stand-in Co-Chair, Complementary methods to study metalloenzymes session, American Crystallographic Association Meeting, Baltimore MD

Lab Techniques and Equipment

Membrane protein and virus production, single particle cryo-electron microscopy, X-ray crystallography, and BLI analyses

Links of Interest

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