Daniel Zegarra-Ruiz

2022 Regional Award Finalist — Post-Doc

Current Position:
Postdoctoral Research Associate

Institution:
Memorial Sloan Kettering Cancer Center

Discipline:
Immunology

Recognized for: Discoveries linking gut microbes to immune processes. The gut microbiome consists of trillions of microbes that impact host immune processes involved in health and disease. Immunologist Daniel Zegarra-Ruiz, PhD, found that during early development, gut bacteria act as a template to educate and increase the number microbiota-specific T cells. These important immune cells recognize gut bacteria and help mount appropriate immune responses. Additionally, changes to the gut microbiome are associated with cancer. Zegarra-Ruiz discovered that, in colorectal cancer, exposing mice to E. coli after tumor initiation can amplify tumor growth but exposure before tumor formation leads to better outcomes. Zegarra-Ruiz’s research is critical to understand the effects bacteria have on the immune system and the consequences on cancer growth as well as inflammatory and autoimmune diseases. 

Areas of Research Interest and Expertise: Immunology, Microbiome, T Cell, Thymus, Lupus, Autoimmunity, Colorectal Cancer

Previous Positions:  

BS, Universidad Peruana Cayetano Heredia, Peru (Advisor: Dr. Jose L. Aguilar-Olano)
PhD, Yale University (Advisor: Dr. Martin A. Kriegel)
Postdoctoral Associate, Baylor College of Medicine (Advisor: Dr. Gretchen E. Diehl)
Postdoctoral Research Fellow, Memorial Sloan Kettering Cancer Center (Advisor: Dr. Gretchen E. Diehl)

Research Summary

The gut microbiome consists of trillions of microbes, and this exceptionally complex microbial community has enormous impacts on health and disease. Immunologist Daniel Zegarra-Ruiz, PhD, has made groundbreaking discoveries regarding how intestinal bacteria modulate the human immune system. Zegarra-Ruiz focuses on a type of immune cell referred to as microbiota-specific T cells. These specialized immune cells recognize gut bacteria and help mount appropriate immune responses. Zegarra-Ruiz established that a type of bacteria called segmented filamentous bacteria (SFB) helps train microbiota-specific T cells. By colonizing the mouse gut with SFB in early life, the number of microbiota-specific T cells increase in the thymus, the immune organ that makes and trains T cells. These findings indicate that the microbiome acts as a template to educate T cells to recognize gut microbiota and fight future bacterial infections.

Zegarra-Ruiz also explores how changes in the gut microbiome influence tumor development in patients with colorectal cancer (CRC). Zegarra-Ruiz performed experiments where he colonized mice with E. coil both before and after tumor initiation. He discovered that colonizing mice with E. coli before tumor initiation protected them from tumor development; however, colonizing with E. coli after tumors were established resulted in tumor acceleration. These results suggest that cells in the intestine relay signals from E. coli that modify the immune processes and ultimately drive CRC outcome.

Studying the interaction between microbes and the immune system can impact our understanding of not only cancer, but also autoimmune diseases where gut microbes play a critical role such as systemic lupus erythematosus, an avenue of research that Zegarra-Ruiz will pursue in the future. 

Perhaps the key to understanding the development of inflammatory and autoimmune disorders hides in our gut.

Key Publications:

1. D.F. Zegarra-Ruiz, D. Kim, K. Norwood, F.B. Saldana-Morales, M. Kim, C. Ng, R. Callaghan, et al. Microbiota manipulation to increase macrophage IL-10 improves colitis and limits colitis-associated colorectal cancer. Gut Microbes, 2022.
2. D.F. Zegarra-Ruiz., D. Kim, K. Norwood, M. Kim, W. Wu, F.B. Saldana-Morales, A.A. Hill, et al. Thymic development of gut-microbiota-specific T cells. Nature, 2021.
3. Zegarra-Ruiz, A. El Beidaq, A.J. Iñiguez, M. Lubrano Di Ricco, S. Manfredo Vieira, W.E. Ruff, D. Mubiru, et al. A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity. Cell Host Microbe, 2019.
4. Manfredo Vieira, M. Hiltensperger, V. Kumar, D.Zegarra-Ruiz, C. Dehner, N. Khan, F.R.C. Costa, et al. Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science, 2018.

Other Honors:

In the Media:

YouTube – Entre mi Casa y el Lab

Andina – Daniel Zegarra, el peruano que destaca en EE.UU. y promueve la ciencia en YouTube

Fred Hutch – Fred Hutch announces recipients of the 4th annual Dr. Eddie Méndez Award

Memorial Sloan Kettering Cancer Center – MSK Awards & Appointments June 2022

Memorial Sloan Kettering Cancer Center – MSK Science Education

Andino – Científico peruano recibe premio en Estados Unidos

Lupus Foundation of America – Daniel Zegarra Ruiz, 2017 Gina M. Finzi Memorial Student Fellow

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