Patricia S. Grace, PhD
- Assistant Professor
Education & Training
- Research Associate, Harvard School of Public Health, 2024
- Postdoctoral Fellow, Ragon Institute of MGH, MIT, and Harvard, 2021
- PhD in Pathology, New York University, 2016
- BS in Chemistry, Mary Baldwin University, 2007
Research Interest Summary
Research Interests
Tuberculosis, the disease caused by the pathogen Mycobacterium tuberculosis (Mtb) remains a global public health burden that takes many lives each year. There is currently no effective vaccine that prevents disease. And an incomplete knowledge about bacterial vulnerabilities that can be targeted by immunity impedes the development of needed new therapies and vaccines.
Antibodies are a powerful and adaptive feature of the immune system that can coordinate potent protective responses during infection. Canonically viewed as antigen specific effectors that neutralize extracellular virus via the antigen binding (Fab) domain, the antibody constant (or Fc-) domain also contributes to pathogen control via interactions with complement or Fc receptors (FcR) expressed on immune cells. Antibodies are a key immune feature that links the TB pathogen to innate and adaptive immunity. The Grace lab uses human and mouse models to:
- Understand the interaction of antibodies with TB antigens
- Identify humoral immune correlates in TB patients associated with favorable infection outcomes
- Define antibody-Fc driven mechanisms that promote bacterial restriction by immune cells
Publications
Grace PS, Peters JM, Sixsmith J, Lu R, Luedeman C, Fenderson BA, Vickers A, Slein MD, Irvine EB, McKitrick T, Wei MH, Cummings RD, Wallace A, Cavacini LA, Choudhary A, Proulx MK, Sundling C, Källenius G, Reljic R, Ernst JD, Casadevall A, Locht C, Pinter A, Sasseti CM, Bryson BD, Fortune SM, Alter G. Antibody-Fab and -Fc features promote Mycobacterium tuberculosis restriction. bioRxiv [Preprint]. 2024 Oct 11:2024.10.07.617070. doi: 10.1101/2024.10.07.617070. PMID 39416184. PMCID: PMC11482752. | View abstract
Irvine EB, Nikolov A, Kahn M, Peters JM, Lu R, Sixsmith J, Wallace A, Schenider M, Shin S, Karpinski W, Hsaio JC, van Woundenbergh E, Casadevall A, Bryson BD, Cavacini LA, Grace PS, Fortune SM, Alter GA. Fc-engineered antibodies leverage neutrophils to drive control of Mycobacterium tuberculosis. Nature Microbiology. 2024 Sep;9(9):2369-2382. doi: 10.1038/s41564-024-01777-9. PMID 39174703. PMCID: PMC11371646. | View abstract
Grace PS, Gunn BM, Lu LL. Engineering the supernatural: monoclonal antibodies for challenging infectious diseases. Curr Opinion Biotechnology. 2022 Dec;78:102818. doi: 10.1016/j.copbio.2022.102818. PMID: 36242952; PMCID: PMC9612313. | View abstract
Grace PS, Dolatshahi S, Lu LL, Cain A, Palmieri F, Petrone L, Fortune SM, Ottenhoff THM, Lauffenburger DA, Goletti D, Joosten SA, Alter G. Antibody Subclass and Glycosylation Shift Following Effective TB Treatment. Frontiers Immunology. 2021 Jul 5;12:679973. doi: 10.3389/fimmu.2021.679973. PMID: 34290702; PMCID: PMC8287567. | View abstract
Lu LL, Chung AW, Rosebrock TR, Ghebremichael M, Yu WH, Grace PS, Schoen MK, Tafesse F, Martin C, Leung V, Mahan AE, Sips M, Kumar MP, Tedesco J, Robinson H, Tkachenko E, Draghi M, Freedberg KJ, Streeck H, Suscovich TJ, Lauffenburger DA, Restrepo BI, Day C, Fortune SM, Alter G. A Functional Role for Antibodies in Tuberculosis. Cell. 2016 Oct 6;167(2):433-443.e14. doi: 10.1016/j.cell.2016.08.072. PMID: 27667685; PMCID: PMC5526202 | View abstract
Grace PS, Ernst JD. Suboptimal Antigen Presentation Contributes to Virulence of Mycobacterium tuberculosis In Vivo. Journal of Immunology. 2016 Jan 1;196(1):357-64. doi: 10.4049/jimmunol.1501494. PMID: 26573837 PMCID: PMC4684992 | View abstract