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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

Location:

Rockville MD

Phone (Primary):

240-314-6396

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, I utilize my expertise in structural biology to investigate inter-organelle communication by multi-subunit membrane protein complexes and viral hijacking of this communciation. Our research has implications for cancer biology, cardiac diseases, infectious viral diseases, and neurodegeneration. 

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

Cancer Biology, Cardiac Disease, Cryo-Electron Microscopy, Epidemic Viruses, G-Proteins, Infectious Viruses, Membrane Proteins, Structural Biology, Transporters, Trans-Membrane Signaling, Viral Structures, Vesicular Trafficking, X-Ray Crystallography

Highlighted Publications

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, Cramer WA. Internal lipid architecture of the hetero-oligomeric cytochrome b6f Structure. 2014;22(7):1008-15. PubMed PMID: 24931468; PubMed Central PMCID: PMC4105968.

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)

Complete List of Publications:

Research Interests

HOW DO ORGANELLES TALK AND VIRUSES EAVESDROP?

          Our research: Biological processes are complex and require coordinated activity of multiple proteins in vastly distinct biochemical environments. Eukaryotic cells are organized into membrane bound organelles that sequester these specialized biochemical environments. The coordinated activity of cellular organelles ensures that complex multi-step biological tasks are executed correctly to maintain cellular homeostasis.

          The Hasan Lab is interested in elucidating the structural basis of communication between specialized organelles that is crucial for metabolic coordination. A major focus of our research is on the secretory pathway in three organelles, i.e., endoplasmic reticulum (ER), Golgi network, and plasma membrane (PM). Nearly one-third of the eukaryotic proteome encodes secretory proteins such as antibodies, hormones, growth-factors, cytokines, and anti-coagulants that function in inter-cellular communication, immunity, and growth. Secretory proteins constitute approximately one-fifth of all known protein drug targets for which an FDA approved therapeutic is available. We are interested in understanding the structural organization of multi-subunit membrane protein complexes that constitute information highways for secretory communication and trafficking between ER, Golgi network, and PM. These membrane protein complexes are highly dynamics in their assembly and composition and involve a variety of membrane embedded components and cytosolic components such as GTPases like signaling G-proteins, and vesicular trafficking coatomer proteins. We aim to elucidate the atomic details of how dysfunction in these signaling-trafficking complexes leads to cancers, cardiac diseases, and neurodegeneration, and to determine the fundamental principles of how these signaling-trafficking complexes are hijacked by epidemic causing SARS-CoV-2, Dengue virus, and pox viruses to achieve viral progeny propagation. Our interest in these viruses is borne out of the large devastation they have caused to human life. Although these viruses are phylogenetically unrelated, they share a common attribute in that they all exploit the human secretory pathway, often through molecular mimicry that tricks human cells to divert host resources towards viral propagation. We hope that comparative investigations of the secretory signaling-trafficking complexes with host and viral proteins will advance the fundamental understanding of cellular metabolism and of diseases such as cancers, cardiac diseases, neurodegeneration, and viral diseases.

          Our tools: Our research mainly uses a combination of latest high-resolution structural technologies such as single particle cryo-electron microscopy (cryo-EM) of large, multi-subunit assemblies and X-ray crystallography and NMR spectroscopy of smaller proteins to gain high-resolution insights into the molecular basis of inter-organelle communication and virus-host interactions. We have in-house access to a new cryo-EM facility that includes a 200 keV Talos Arctica TEM equipped with a Falcon 3 direct electron detector. A second 200 keV TEM, a Glacios, is currently being installed with a K3 direct electron detector and a Volta Phase Plate. We have access to a 950 MHz NMR spectrometer and latest crystallographic data-collection facilities, which complement our cryoEM investigations.

          Our collaborations: Our structural research is enriched by collaborative HDX mass spectrometry of conformational dynamics of membrane protein and viral protein complexes, mass spectrometry-based lipidomics, molecular dynamics, and computer assisted drug design.

           Vacancies: We are always looking for post-doctoral researchers interested in structural investigations of membrane protein complexes and assembly of epidemic causing viruses. Feel free to drop an email to Saif to enquire about available positions. 

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)

Lab Techniques and Equipment

Single particle cryo-electron microscopy, X-ray crystallography, fluorescence spectroscopy, circular dichroism spectroscopy

Links of Interest