Jeoung-Sook Shin, Ph.D.

Associate Professor, Department of Microbiology & Immunology
Sandler Asthma Basic Research Center
University of California San Francisco

513 Parnassus Avenue, HSE-201
San Francisco, CA 94143-0414

Tel: 415-476-5451
Fax: 415-476-3939
Email: [email protected]

Jeoung-Sook Shin is an Associate Professor in the Department of Microbiology & Immunology. She completed her B.S. and M.S. in Chemistry at Seoul National University, Korea. She received her Ph.D. from Duke University and her postdoctoral training at Yale University as a Jane Coffin Childs Memorial Fund Postdoctoral Fellow.

The Shin laboratory is interested in understanding the molecular mechanisms by which dendritic cells shape and control T cell immunity. The current research is focused on understanding the role of a membrane-anchored ubiquitin ligase named MARCH1 (membrane-associated RINCCH1). MARCH1 is highly expressed in dendritic cells, attaches ubiquitin chains to the cytoplasmic tail of MHCII, CD86, and possibly other membrane proteins, and mediates endocytosis, lysosomal sorting, and degradation of the substrates. Through this activity, MARCH1 promotes surface turnover of specific immune-associated molecules in dendritic cells. However, its functional role is not clearly understood.

The specific objectives are as follows:

  1. Determine the role of MARCH1 in dendritic cell function of establishing T cell tolerance. Dendritic cells play a significant role in establishing T cell tolerance through their ability to present self-antigens to developing T cells in the thymus. When antigen-presenting DCs make a cognitive interaction with antigen-specific thymocytes, this interaction leads the engaged thymocytes to apoptotic cell death or regulatory T cell differentiation. Whether MARCH1 is involved in any of these processes is being investigated.
  2. Determine the role of MARCH1 in dendritic cell function of driving T cell immunity. Dendritic cells play an essential role in the development of specific T cell immunity to various antigens. Dendritic cell subset 1 drives cytotoxic T lymphocyte and T helper type 1 (Th1) immunity against virus, cancer, and intracellular bacteria or parasite whereas dendritic cell subset 2 drives Th17 immunity to fungi and extracellular bacteria and Th2 immunity to intestinal hookworm and allergens. The Shin laboratory is interested in finding out whether MARCH1 plays an important role in the development and maintenance of any specific types of T cell immunity.
  3. Determine the role of MARCH1 in immune-stimulatory diseases. Many of immunestimulatory diseases are associated with unregulated T cell immunity. Allergic diseases including allergic asthma are associated with strong Th2 immunity while certain autoimmune diseases such as multiple sclerosis are associated with strong Th1 and Th17 immunity. The Shin laboratory is interested in determining whether MARCH1 is involved in the development and exacerbation of these T cell-dependent immune-stimulatory diseases and if so, whether MARCH1 could serve as a therapeutic target for treatment of these diseases.
Selected Publications:
  1. Shin, JS, Gao, Z, Abraham, SN. Involvement of cellular caveolae in bacterial entry into mast cells. Science. 289:785-8, 2000.
  2. Shin JS, Abraham SN. Cell biology. Caveolae--not just craters in the cellular landscape. Science. 293:1447-8, 2001.
  3. Shin, JS, Shelburne, CP, Jin, C, LeFurgey, EA, Abraham, SN. Harboring of particulate allergens within secretory compartments by mast cells following IgE/FceRI-lipid raft mediated phagocytosis, J Immunol. 177:5791-5800, 2006
  4. Shin, JS, Ebersold, M, Pypaert, M, Delamarre, L, Hartley, A, and Mellman, I. Surface expression of MHC class II in dendritic cells is controlled by regulated ubiquitination, Nature. 444:115-8, 2006
  5. Bloom, O, Unternaehrer, JJ, Jiang, A, Shin, JS, Delamarre, L, Allen, P, and Mellman, I. Spinophilin participates in information transfer at immunological synapses, J Cell Biol. 181:203-11, 2008
  6. Baravalle, G, Park, H, McSweeney, M, Ohmura-Hoshino, M, Matsuki, Y, Shin, JS. Ubiquitination of CD86 is a key mechanism in regulating antigen presentation by dendritic cells, J Immunology. 187:2966, 2011
  7. Ma, JK, Platt, MY, Eastham-Anderson, J, Shin, JS*, and Mellman, I*. MHC class II distribution in dendritic cells and B cells is determined by ubiquitin chain length, PNAS. 109:8820, 2012 *Shin, JS and Mellman, contributed equally to this work
  8. Oh, J, Wu, N, Baravalle, G, Cohn, B, Ma, J, Lo, B, Mellman, I, Ishido, S, Anderson, M, and Shin, JS. MARCH1-mediated MHCII ubiquitination promotes dendritic cell selection of natural regulatory T cells, J Exp Med. 210:1069, 2013
  9. Greer, A, Wu, N, Putnam, A, Woodruff, P, and Shin, JS. Serum IgE clearance is facilitated by human FceRI internalization. J Clin Inves. 124:1187, 2014
  10. Baravalle, G, Greer, A, LaFlam, TN, and Shin, JS. Antigen-conjugated human IgE induces antigen-specific T cell tolerance in a humanized mouse model, J Immunology. 192:3280, 2014
  11. Greer, AM, Matthay, MA, Kukreja, J, Bhakta, NR, Nguyen, CP, Wolters, PJ, Woodruff, PG, Fahy, JV, and Shin, JS. Accumulation of BDCA1+ dendritic cells in interstitial fibrotic lung diseases and Th2-high asthma. PLoS ONE, Jun 9(6): e99084, 2014
  12. Greer, AM and Shin, JS. The Role of FceRI expressed by dendritic cells and monocytes. Cellular and Molecular Life Sciences. 72:2349, 2015
  13. Oh J, Shin, JS. Molecular mechanism and cellular function of MHCII ubiquitination. Immunological reviews. 266:134, 2015.
  14. Bannard O, McGowan SJ, Ersching J, Ishido S, Victora GD, Shin JS, and Cyster JG. Ubiquitin-mediated fluctuations in MHCII class II facilitate efficient germinal center B cell responses. J Exp Med. 213:993, 2016
  15. Oh, J, Wu, N, Barczak, AJ, Barbeau, R, Erle, DJ, and Shin, JS. CD40 mediates maturation of thymic dendritic cells driven by self-reactive CD4+ thymocytes and supports development of natural regulatory T cells. J Immunology, 200:1399, 2018
  16. Oh. J, Perry, JSA, Pua, H, Irgens-Moller, N, Ishido, S, Hsieh, CS, and Shin, JS. MARCH1 protects the lipid raft and tetraspanin web from MHCII proteotoxicity in dendritic cells. J Cell Biol, 217:1395, 2018
  17. Borges TJ, Murakami N, Machado FD, Murshid A, Lang BJ, Lopes RL, Bellan LM, Uehara M, Antunes KH, Pérez-Saéz MJ, Birrane G, Vianna P, Gonçalves JIB, Zanin RF, Azzi J, Abdi R, Ishido S, Shin JS, Souza APD, Calderwood SK, Riella LV, Bonorino C. MARCH1-dependent modulation of donor MHC II on CD103+ dendritic cell mitigates alloimmunity. Nat Commun, 9: 3482, 2018
  18. Shin JS. Unexpected role of dendritic cells in pulmonary fibrosis. Thorax, 74:925, 2019
  19. Deng Z, Law CS, Ho FO, Wang KM, Jones KD, Shin JS, Shum AK. A defect in thymic tolerance causes T cell-mediated autoimmunity in a murine model of COPA syndrome. J Immunology, 204:2360, 2020