Research

Researches

Sumana SANYAL Lab

Sumana SANYAL, BSc(Hons), MSc, PhD


Assistant Professor
Division of Public Health Laboratory Sciences, School of Public Health
School of Biomedical Sciences
The University of Hong Kong

Contact Information
Tel: +852 2831 5524     Email: sanyal@hku.hk
Address: 7/F Hong Kong Jockey Club Building for Interdisciplinary Research, 5 Sassoon Road, Hong Kong

Profile / Projects / PhD projectsPublications / CV / Lab

Profile

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Projects

Our group focuses on understanding host-pathogen interactions that orchestrate an outcome between a successful virus infection versus host restriction. Centered on Dengue and Influenza viruses, we combine biochemical techniques with that of imaging and molecular biology to understand the role of ubiquitin and ubiquitin like modifiers in shaping protein trafficking and cellular signaling pathways by modulating the function of both host and virus-derived factors. Our three ongoing projects are:

  1. Identification and characterization of host factors involved in Dengue virus infection
  2. Role of deubiquitylation events during virus infection
  3. Role of interferon stimulated gene 15 (ISG15) in host restriction of virus infections

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PhD Projects

Project 1: Host factors involved in dengue virus release
The host cellular machinery required for Dengue virus biogenesis is not understood. We have identified Aup1 as one of the host factors that is highly upregulated upon dengue in- fection. Aup1 is a Type-III membrane protein that has been shown to play a role in lipid droplet formation and in the process of endoplasmic reticulum associated degradation. Our ongoing research involves monitoring dengue virus particle release in a non-infectious set- ting, to examine the role of Aup1 in virus particle budding. Upon overexpression of Aup1 we observe an increase in the release of Dengue VLPs, suggesting that Aup1 itself facilitates Dengue secretion. Preliminary data suggests that this function of Aup1 is inhibited upon ubiquitylation. We have generated several variants of Aup1 that are mutated in different domains of the protein. These will be combined with Dengue VLPs in HeLa cells to identify the functional domain of Aup1 responsible for the process of virus release.

Project 2: Role of deubiquitylating enzymes (DUB) in innate immune sig- naling pathways and during viral infections
We use strategies to selectively isolate deubiquitylating enzymes (DUB) that play a role in different cellular pathways. We employ this strategy to identify those that function to tar- get immune signaling pathways, particularly upon infection by various pathogens such as viruses. Some viruses are equipped with their own deubiquitylating enzyme that can inhibit host immune responses. Influenza does not express its own DUB; however, they are able to manipulate the host cellular machinery to upregulate DUBs that provide a replicative advan- tage to them. We use a ubiquitin variant C-terminally modified with vinyl methyl ester (Ub- VME) that can react with active site cysteines of DUBs and can be used to isolate those that are expressed during infection. We have identified several DUBs that are recruited during T- cell receptor signaling as well as two that are specifically expressed upon influenza infection. At present we are investigating the functional relevance of these DUBs during immune sig- naling and virus infections through generating CRISPR-mediated inducible knock-out cells.

Project 3: Function of Tsg101 during influenza infection and its modulation by the interferon-I response
A major response of mammalian cells to viral infections is through upregulation of the in- terferon type I and II pathways. Viruses in turn counter this pathway through either the inhibition of IFN response or by activation of proteins that inhibit the function of interferon- stimulated genes (ISGs). Most viruses including influenza have evolved clever strategies to circumvent the immune response to execute a productive infectious cycle. Influenza achieves this through the function of its non-structural protein 1 (NS1). NS1 has been suggested to be the virulence determining component in influenza viruses and hence understanding its function in the context of virus-host interactions and potential to target the host immune system is of paramount importance. A key interaction documented for NS1 is the dynam- ics of interaction with the interferon-stimulated gene 15 (ISG15). Upon type-I interferon treatment or virus infection, ISG15 is one of the immediate responders and is expressed in abundance. The identities of all the ISG15 targets have not been identified yet. We have identified Tsg101 as one of the host factors involved in assembly and release of infectious virus particles. Tsg101 itself is ISG15 modified upon interferon induction, which prevents virus release from infected cells. We are currently using techniques in cell and molecular bi- ology to understand the role of Tsg101 in influenza biogenesis, the role of post-translational modification (phosphorylation, Isgylation) of Tsg101 for modulation of its function and the contribution of flu NS1 in counteracting the activity of Tsg101 and ISG15.

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Publications

  1. Sanyal S, Ashour J, Maruyama T, Altenburg AF, Cragnolini JJ, Bilate A, Avalos AM, Garcia-Sastre A and Ploegh HL. Type-I interferon imposes a Tsg101/ISG15 checkpoint at the Golgi for glycoprotein trafficking during influenza virus infection (2013) Cell Host Microbe 14(5): 510-521
  2. Reiling JH, Olive AJ, Sanyal S, Carette JE, Brummelkamp TR, Ploegh HL, Starnbach MN and Sabatini DM. A Luman/CREB3–ADP-ribosylation factor 4 (ARF4) signaling pathway mediates the response to Golgi stress and susceptibility to pathogens (2013) Nat Cell Biology 15(12): 1473-1485.
  3. Tafesse F, Sanyal S, Ashour J, Guimaraes CP, Hermansson M, Somerharju P and Ploegh H. (2013) Intact sphingomyelin biosynthetic pathway is essential for intracellular transport of Influenza virus glycoproteins Proc Natl Acad Sci USA 110(16): 6406-6411
  4. Sanyal S, Claessen JHL and Ploegh H (2012) A viral deubiquitylating enzyme restores dislocation of substrates from the Endoplasmic Reticulum (ER) in semi-intact cells. J. Biol. Chem 287(28): 23594-23603
  5. Ernst R, Claessen JHL, Mueller B, Sanyal S, Spooner E, van der Veen AG, Kirak O, Schlieker C, Weihofen WA and Ploegh H (2011) Enzymatic blockade of the ubiquitin proteasome pathway. PLoS Biol 8(3): e1000605
  6. Menon I, Huber T, Sanyal S, Banerjee S, Barre P, Canis S, Warren JD, Hwa J, Sakmar T and Menon AK (2011) Opsin is a phospholipid flippase in disk membranes. Curr Biol 21(2): 149-153
  7. Sanyal S and Menon AK (2010) Stereoselective transbilayer translocation of mannosyl phosphoryl dolichol by an endoplasmic reticulum flippase. Proc Natl Acad Sci USA 107(25): 11289-11294
  8. Sanyal S and Menon AK (2009) Flipping lipids: Why an’ what’s the reason for? ACS Chem Biol; Invited review 4(11): 895-909
  9. Sanyal S and Menon AK (2009) Specific transbilayer translocation of dolichol-linked- oligosaccharides by an endoplasmic reticulum flippase. Proc Natl Acad Sci USA 106(3): 767-772
  10. Frank CG, Sanyal S and Menon AK (2008) Does Rft1 flip an N-glycan lipid precursor? Nature 454(7204): E3-4
  11. Sanyal S, Frank CG, Menon AK (2008) Distinct flippases translocate glycerophospholipids and oligosaccharide diphosphate dolichols across the endoplasmic reticulum. Biochemistry 47(30): 7937-7946 (ACS Chemical Biology spotlight, Vol 3 No. 8)
  12. Sutterwala SS, Creswell CH, Sanyal S, Menon AK and Bangs JD (2007) De novo sphingolipid synthesis is essential for viability, but not for transport of glycosylphosphatidylinositol-anchored proteins, in African trypanosomes. Eukaryot Cell 6(3): 454-464

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CV

Education:
2005-2010: Cornell University, Weill Cornell Medical College, New York, Ph.D (Biochemistry/Chemical Biology): August 2010
2003-2005: Indian Institute of Technology, Delhi, Master of Science in Chemistry
2000-2003: St. Stephen’s College, University of Delhi, Bachelor of Science (Honours) in Chemistry

Working Experience:
2016-present:HKU-Pasteur Research Pole, School of Public Health, School of Biomedical Sciences, HKU, Assistant Professor
2011-2013: HKU-Pasteur Research Pole, School of Public Health, HKU, Research Assistant Professor
2010-2013: Whitehead Institute for Biomedical Research, MIT
Postdoctoral Research Associate (with Prof. Hidde Ploegh)

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Lab

  • Akhee Jahan (PhD Student)
  • Yun Lan (Post-doctoral Fellow)
  • Mingyuan Li (Post-doctoral Fellow)
  • João Pombo (MPhil Student)
  • Lewis Siu (Research Technician)
  • Tami Zhang (Post-doctoral Fellow)

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