Law Laboratory | Scripps Research

Research

The Yin and Yang of Human Antibody Response

Antibody response is part of our immune reactions to fight invasion of foreign matters and development of cancer in our bodies. It is a continuous trial-and-error process throughout our lifetime, influenced by both internal and external factors. When error occurs, our antibody response can do harm to ourselves.

The Law laboratory is interested in understanding how the good and the bad antibodies are made in our bodies. The good antibodies, made during an infection or vaccination against pathogens, help us survive numerous infections. The bad antibodies, found in autoimmune diseases and allergies, contribute to chronic health problems leading to poor quality of life.

Current research projects:

(1) Hepatitis C (HCV). We are one of the leading teams in the world in the study of HCV neutralizing antibodies and vaccine antigens for rational vaccine design. See our recent publications here for our strategies in the development of a broadly effective HCV vaccine.

(2) Hepatitis B (HBV). It is estimated that ~5% of the world populations are HBV+. Chronic HBV can lead to liver inflammation and loss of liver functions. HBV is the leading cause for the need of liver transplantation in many countries. Chronic HBV can be cured functionally when the virus surface antigen (HBsAg) is suppressed and anti-HBsAg antibodies are produced at a high level in the patients. It is recently reported that antibody and B cell responses in chronic HBV patients are defective. We are interested in learning about the mechanism of this virus-induced immune suppression and the strategies to reverse the defect.

(3) Rheumatoid factor (RF) in protection and human diseases. RF is an anti-antibody antibody made in our bodies during an infection or autoimmune reaction. In chronic viral infection, RF can form large immune complex that precipitates in lower body temperature, known as cryoglobulin, causing tissue inflammation and damage. We would like to better define the molecular properties of RF and how they are regulated in our bodies.

(4) Food allergy. Allergy is a “misfired” immune reaction when our bodies expose to harmless food/environmental antigens. The exact cause of allergy is poorly understood although we know that IgE antibody plays a role if the allergic reaction occurs within minutes of allergen exposure. Allergen-specific IgE captured on the surface of mast cells can detect the presence of allergens, leading to "mast cell degranulation" and a cascade of potent immune reactions resulting in tissue damage, and in severe cases, life-threatening anaphylactic reaction. We are interested in studying how the allergen-specific IgE B cells are generated, how the immune memory to food allergens is maintained, and the strategies in curing food allergy. A collaborative training program has been established between our lab and the Division of Allergy, Asthma and Immunology of Scripps Clinic to study peanut allergy.

Mansun Law, Ph.D.

Associate Professor
Department of Immunology & Microbiology

Education
B.Sc., Biotechnology, University of Hong Kong
M.Phil., Molecular Biology, University of Hong Kong
D.Phil., Virology, University of Oxford

Personnel

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Erick Giang

Sr. Research Assistant

Fang Chen

Staff Scientist

Areeje Almasary

Postdoc Fellow

Natalie Shoanga

Research Technician

Alumni

Name Position Date
DAE HEE KIM VISITING SCIENTIST 2020 - 2021
ADAM AZAI RESEARCH INTERN 2019 - 2021
WHITNEY BALDRIDGE GRADUATE STUDENT 2019 - 2021
DUYEN TRAN RESEARCH INTERN 2017 - 2020
KENNA NAGY RESEARCH ASSISTANT 2016 - 2019
JENNIFER CHOI RESEARCH INTERN 2016 - 2019
ESTELLE QI HIGH SCHOOL INTERN 2018 - 2019
JI HYUN LEE HIGH SCHOOL INTERN 2018 - 2019
SHAUN CASTILLO STUDENT INTERN / RESEARCH ASSISTANT 2012 - 2018
FERNANDO ALEMAN (PH.D.) RESEARCH ASSOCIATE 2014 - 2018
GERMAN GOMEZ VISITING SCIENTIST 2016 - 2017
XIHUA CAO VISITING SCIENTIST 2016 - 2017
RADHIKA GOPAL (PH.D) RESEARCH ASSOCIATE 2016 - 2017
KALIFA STRINGFIELD SURF STUDENT 2017
MATTHEW WANG SUMMER HIGH SCHOOL STUDENT 2017
ALEX SWEY-SHEN CHEN (D.SC.) VISITING SCIENTIST 2015 - 2017
ANDREW HONDA RESEARCH ASSISTANT 2013 - 2017
DEVAN CHEA STUDENT INTERN 2014 - 2016
MICHELLE ZHI XU (M.D./PH.D.) VISITING SCIENTIST 2015 - 2016
JESSICA REINHARD VISITING STUDENT 2015
KELLI JACKSON GRAD STUDENT 2013 - 2015
JUDY JUN STUDENT INTERN 2011 - 2014
TINASHE RUWONA (PH.D.) RESEARCH ASSOCIATE 2010 - 2014
JUSTIN LUU RESEARCH INTERN 2013
TRAVIS NIEUSMA STUDENT INTERN / RESEARCH ASSISTANT 2009 - 2012
JUSTIN ROBBINS (PH.D.) RESEARCH ASSOCIATE 2009 - 2012
KRISTIN COGBURN RESEARCH ASSISTANT 2009 - 2012
ANNE DUE (PH.D.) RESEARCH ASSOCIATE 2010 - 2012
NANCY FONG STUDENT INTERN 2011 - 2012
JILL ROUGHAN (PH.D.) RESEARCH ASSOCIATE 2009 - 2012
KATHRYN REARDON SURF STUDENT / RESEARCH ASSISTANT 2009 - 2011
ARTHUR KIM STUDENT INTERN 2009 - 2011
ROSA CARDOSO (PH.D.) RESEARCH ASSOCIATE 2009 - 2010

Photos

Contact

Law Laboratory
Department of Immunology and Microbiology
The Scripps Research Institute

10550 N. Torrey Pines Rd.
Room/Mailcode: IMM33
La Jolla, CA 92037
Phone - (858) 784-2383
Fax - (858) 784-7842

Publications

See full list of publications by Mansun Law here

Review:

  1. Law M. (2021) Antibody Responses in Hepatitis C Infection. Cold Spring Harb Perspect Med. 11(3). https://doi.org/10.1101/cshperspect.a036962
  2. Chen F, Tzarum N, Wilson IA, Law M. (2019) VH1-69 antiviral broadly neutralizing antibodies: genetics, structures, and relevance to rational vaccine design. Curr Opin Virol 34:149-59. https://doi.org/10.1016/j.coviro.2019.02.004
  3. Tzarum N, Wilson IA, Law M. (2018) The neutralizing face of hepatitis C virus E2 envelope glycoprotein. Front Immunol 9:1315. https://doi.org/10.3389/fimmu.2018.01315

Research Article:

  1. Chen F, Tzarum N, Lin X, Giang E, Velázquez-Moctezuma R, Augestad EH, Nagy K, He L, Hernandez M, Fouch ME, Grinyó A, Chavez D, Doranz BJ, Prentoe J, Stanfield RL, Lanford R, Bukh J, Wilson IA, Zhu J, Law M. (2021) Functional convergence of a germline-encoded neutralizing antibody response in rhesus macaques immunized with HCV envelope glycoproteins. Immunity. 54:781-796.e4. https://doi.org/10.1016/j.immuni.2021.02.013
  2. Chen F, Nagy K, Chavez D, Willis S, McBride R, Giang E, Honda A, Bukh J, Ordoukhanian P, Zhu J, Frey S, Lanford R, Law M. (2020) Antibody responses to immunization with HCV envelope glycoproteins as a baseline for B cell-based vaccine development. Gastroenterology 158:1058-1071.e6. https://doi.org/10.1053/j.gastro.2019.11.282
  3. Tzarum N, Giang E, Kadam RU, Chen F, Nagy K, Augestad EH, Velázquez-Moctezuma R, Keck ZY, Hua Y, Stanfield RL, Dreux M, Prentoe J, Foung SKH, Bukh J, Wilson IA, Law M. (2020) An alternate conformation of HCV E2 neutralizing face as an additional vaccine target. Sci Adv 6:eabb5642. https://doi.org/10.1126/sciadv.abb5642
  4. Tzarum N, Giang E, Kong L, He L, Prentoe J, Augestad E, Hua Y, Castillo S, Lauer GM, Bukh J, Zhu J, Wilson IA, Law M. (2019) Genetic and structural insights into broad neutralization of hepatitis C virus by human VH1-69 antibodies. Sci Adv 5:eaav1882. https://doi.org/10.1126/sciadv.aav1882
  5. Aleman F, Tzarum N, Kong L, Nagy K, Zhu J, Wilson IA, Law M. (2018) Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors. Proc Natl Acad Sci U S A 115:7569-74. https://doi.org/10.1073/pnas.1802378115
  6. Gopal R, Jackson K, Tzarum N, Kong L, Ettenger A, Guest J, Pfaff JM, Barnes T, Honda A, Giang E, Davidson E, Wilson IA, Doranz BJ, Law M. (2017) Probing the antigenicity of hepatitis C virus envelope glycoprotein complex by high-throughput mutagenesis. PLoS Pathog 13:e1006735. https://doi.org/10.1371/journal.ppat.1006735
  7. Kong L, Lee DE, Kadam RU, Liu T, Giang E, Nieusma T, Garces F, Tzarum N, Woods VL, Jr., Ward AB, Li S, Wilson IA, Law M. (2016) Structural flexibility at a major conserved antibody target on hepatitis C virus E2 antigen. Proc Natl Acad Sci U S A 113:12768-73. https://doi.org/10.1073/pnas.1609780113
  8. Kong L, Giang E, Nieusma T, Kadam RU, Cogburn KE, Hua Y, Dai X, Stanfield RL, Burton DR, Ward AB, Wilson IA, Law M. (2013) Hepatitis C virus E2 envelope glycoprotein core structure. Science 342:1090-4. https://doi.org/10.1126/science.1243876
  9. Giang E, Dorner M, Prentoe JC, Dreux M, Evans MJ, Bukh J, Rice CM, Ploss A, Burton DR, Law M. (2012) Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus. Proc Natl Acad Sci U S A 109:6205-10. https://doi.org/10.1073/pnas.1114927109
  10. Law M, Maruyama T, Lewis J, Giang E, Tarr AW, Stamataki Z, Gastaminza P, Chisari FV, Jones IM, Fox RI, Ball JK, McKeating JA, Kneteman NM, Burton DR. (2008) Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge. Nat Med 14:25-7. https://doi.org/10.1038/nm1698

Research Reagents

The below monoclonal antibodies are now available through EMD Millipore:

  •      Anti-HCV E2 Antibody, clone 19B3
  •      Anti-HCV E2 Antibody, clone AR1B
  •      Anti-HCV E2 Antibody, clone AR3A
  •      Anti-HCV E1E2 Antibody, clone AR5A

For large quantity of the mAbs, or other mAbs/antigens, please email H. Ibarra (hibarra@scripps.edu)