Alter

Galit Alter, PhD

Lab Info:

Principal Investigator: Galit Alter, PhD

Lab Staff: 6 research staff scientists, 14 post docs, 5 graduate students, 2 undergraduate students, 7 technicians, 3 administrators

Office/Location: 400TS 784

Phone: (857) 268-7003

Email: galter@partners.org

Category: Group Leaders, Members

Dr. Galit Alter is a Professor of Medicine at Harvard Medical School and a Group Leader at the Ragon Institute of MGH, MIT and Harvard.

 

Dr. Alter’s work focuses on the development of systems biology tools to define the correlates of immunity against infectious diseases that ravage the globe. To this end, Dr. Alter developed a novel, ever-evolving approach to probing humoral immunity that she termed ‘systems serology’. Dr. Alter uses this novel -omics platform to profile the remarkable diversity of antibodies generated in response to pathogens or vaccines and their abilities to leverage the immune system to fight disease. Capturing hundreds of datapoints, this approach provides unprecedented resolution into the unique humoral immune fingerprints that exist among individuals. Her group then interrogates these antibody profiles, using machine learning and other high dimensional tools to define the specific antibody profiles/features that track with favorable patient outcomes in diseases such as HIV, Ebola virus, Mycobacterium tuberculosis, malaria, etc. These data raise often unexpected hypotheses on antibody mechanism of action that have led to the accelerated understanding of new therapeutic or vaccine-design approaches.

 

Through this work, Dr. Alter seeks to advance rational vaccine design as well as begin to define the rules by which vaccines may fully leverage the breadth of functionality of the humoral immune response. By increasing the understanding of humoral immunity, she aims to expand the focus of vaccine development from effective antigen design to include the frequently overlooked role of antibodies in directing innate immune activity. This novel direction in systems immunology also may point to innovative engineering strategies to enhance the bioactivity of the monoclonal therapeutics aimed at selectively driving clearance, control, or eradication of diseases beyond those caused by infectious agents, including malignancies and autoimmune disorders.

 

Most recently, Dr. Alter has become particularly interested in the role of post-translational modulation of antibody functionality, via alterations in the glycans that are added to antibodies. Like all glycoproteins, antibody glycosylation changes rapidly during inflammatory diseases. Interestingly, these changes in glycosylation have direct effects on tuning antibody effector function. Dr. Alter’s work points to directed changes in antibody glycosylation linked to disease control. Understanding the rules by which antibody glycosylation, and more broadly all protein glycosylation, is controlled to direct immunologic activity may unlock new avenues to manipulate antibody function in a targeted manner through vaccination.

 

Dr. Alter is a two-time recipient of the prestigious MGH Research Scholars Award, and she was elected a member of the American Association of Microbiology in 2019.

 

Dr. Alter received a BSc and PhD at McGill University and completed postdoctoral training in the Partners AIDS Research Center at MGH.

 

Noteworthy Publications

1. Ackerman ME, Das J, Pittala S, Broge T, Linde C, Suscovich TJ, Brown EP, Bradley T, Natarajan H, Lin S, Sassic JK, O’Keefe S, Mehta N, Goodman D, Sips M, Weiner JA, Tomaras GD, Haynes BF, Lauffenburger DA, Bailey-Kellogg C, Roederer M, Alter G. Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV. Nat Med. 2018 Oct;24(10): 1590-1598.

 

2. Lofano G, Gorman MJ, Yousif AS, Yu WH, Fox JM, Dugast AS, Ackerman ME, Suscovich TJ, Weiner J, Barouch D, Streeck H, Little S, Smith D, Richman D, Lauffenburger D, Walker BD, Diamond MS, and Alter G. Antigen-specific antibody Fc-glycosylation enhances humoral immunity via the recruitment of complement. Science Immunology. 2018. Aug 17;3(26). pii: eaat7796. PMID: 30120121.

 

3. Yu WH, Zhao P, Draghi M, Arevalo C, Karsten CB, Suscovich TJ, Gunn B, Streeck H, Brass AL, Tiemeyer M, Seaman M, Mascola JR, Wells L, Lauffenburger DA, Alter G. Exploiting glycan topography for computational design of Env glycoprotein antigenicity. PLoS Comput Biol. 2018 Apr 20;14(4):e1006093. doi: 10.1371/journal.pcbi.1006093.

 

4. Lu LL, Chung AW, Rosebrock T, Ghebremichael M, Yu WH, Schoen MK, Tafesse F, Martin C, Leung V, Mahan AE, Sips M, Tedesco J, Robinson H, Tkachenko E, Freedberg, Streeck H, Suscovich TJ, Draghi M, Lauffenburger D, Restrepo BI, Day C, Fortune S, Alter G. A functional role for antibodies in tuberculosis. Cell. 2016 Oct 6;167(2):433-443.e14.

 

5. Alison E. Mahan, Madeleine F. Jennewein, Todd Suscovich, Kendall Dionne, Jacquelynne Tedesco, Amy W. Chung, Hendrik Streeck, Maria Pau, Hanneke Schuitemaker, Don Francis, Patricia Fast, Dagna Laufer, Bruce D. Walker, Lindsey Baden, Dan H. Barouch, Galit Alter. Antigen-specific antibody glycosylation is regulated via vaccination. PLOS Path. 2016 Mar 16;12(3):e1005456.

 

6. Chung AW, Kumar MP, Arnold KB, Yu WH, Schoen MK, Dunphy LJ, Suscovich TJ, Frahm N, Linde C, Mahan AE, Hoffner M, Streeck H, Ackerman ME, McElrath JM, Schuitemaker H, Pau MG, Baden L, Kim JH, Michael NL, Barouh DH, Lauffenburger. DA, Alter G. Dissecting polyclonal vaccine-induced humoral immunity against HIV using Systems Serology. Cell. 2015 Nov 5;163(4):988-98.

 

7. Alter G, Heckerman D, Schneidewind A, Fadda L, Kadie CM, Carlson JM, Oniangue-Ndza C, Martin M, Li B, Khakoo SI, Carrington M, Allen TM, Altfeld M. HIV-1 adaptation to NK-cell-mediated immune pressure. Nature. 2011 Aug 3;476(7358):96-100.

 

Reviews

1. Saphire EO, Schendel SL, Gunn BM, Milligan JC, Alter G. Antibody-mediated protection against Ebola virus. Nat Immunol. 2018 Nov;19(11):1169-1178.

 

2. Alter G, Barouch D. Immune Correlate-Guided HIV Vaccine Design. Cell Host Microbe. 2018 Jul 11;24(1):25-33.

 

3. Fadda L and Alter G. KIR/HLA: Genetic Clues for a Role of NK cells in the Control of HIV. Adv Exp Med Biol. 2012; 780:27-36.

 

4. Ackerman ME, Dugast AS, Alter G. Emerging concepts on the role of innate immunity in the prevention and control of HIV infection. Annu Rev Med. 2012;63:113-30. Epub 2011 Nov 8.

 

5. Alter G, Altfeld M. Mutiny or scrutiny: NK cell modulation of DC function in HIV-1 infection. Trends Immunol. 2011 May;32(5):219-24. Epub 2011 Mar 14.

 

6. Berger CT, Alter G. Natural Killer cells in spontaneous control of HIV infection. CurrOpin HIV AIDS. 2011 May;6(3):208-13.

 


Laboratory Staff:

 

Research Staff:

Thomas Broge, Technologist

Jon Fallon, PhD, Staff Scientist

Bronwyn Gunn, PhD, Senior Research Scientist

Caitlyn Linde, Research Specialist

Richard Lu, PhD, Research Specalist

Vicky Roy, Technologist

Todd Suscovich, PhD, Senior Research Lab Manager

 

Fellows:

Yannic Bartsch, PhD, Postdoctoral Fellow

Zhilin Chen, PhD, Postdoctoral Fellow

Deniz Cizmeci, PhD, Postdoctoral Fellow

Jishnu Das, PhD, Postdoctoral Fellow

Leela Davies, MD, PhD, Infectious Disease Fellow

Allison Demas, PhD, Postdoctoral Fellow

Elizabeth DeRiso, PhD, Postdoctoral Fellow

Sepideh Dolatshahi, PhD, Postdoctoral Fellow

Matthew Gorman, PhD, Postdoctoral Fellow

Patricia Grace, PhD, Postdoctoral Fellow

Jonathan Herman, PhD, Infectious Disease Fellow

Christina Karsten, PhD, Postdoctoral Fellow

Nickita Mehta, PhD, Postdoctoral Fellow

Evan Rossignol, PhD, Postdoctoral Fellow

Aniruddh Sarkar, PhD, Postdoctoral Fellow

Marianna Spatola, PhD, Postdoctoral Fellow

 

Graduate Students:

Caroline Atyeo

Carolyn Boudreau

Audrey Butler

Stephanie Fischinger

Edward Irvine

Madeleine Jennewein

Alex Zhu

Tomer Zohar

 

Technicians:

Jackson Burke

Thomas Linnekin

Wiktor Karpinski

Ashlin Michell

Sally Shin

Matthew Slein

Administrators:

Corinne Luedemann, Project Manager

Madeline Davis, Project Coordinator

 

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