Sharma Lab

Sharma Lab

"We’re trying to harness the potential of the genome. At our Center, you can systematically dissect the genome by simultaneously conducting thousands of automated experiments to learn how genes function in relation to a given biological system of interest. I think that’s incredibly exciting." — Sonia Sharma, Ph.D. // Assistant Professor, Director
Division of Cell Biology

Overview

Sonia Sharma’s current research focuses on using unbiased, genome-scale approaches to unravel innate immunity, the body’s early immune response to microbial pathogens and neoplastic cells, which has also been implicated as a common causal factor in many inflammatory, allergic and autoimmune diseases. She integrates cutting-edge genetics, biochemistry, cell biology, computational and translational approaches to define the key genetic mechanisms regulating cellular innate immunity, and determine how they impact human health and disease.

Dr. Sharma has an outstanding record of research accomplishments, including high impact discoveries published in top scientific journals. Her work has made her an internationally recognized expert in the use of high throughput, genome scale approaches, in particular RNA interference and CRISPR/Cas9, to dissect complex cellular signaling pathways and questions of immunological relevance. Her use of these technologies is a powerful tool that can be applied to any cellular pathway or disease process.

Dr. Sharma was instrumental in establishing the Institute’s Functional Genomics Center, which she currently directs, and she is channeling her expertise to further her own research program. Her work, particularly her studies of anti-viral and anti-tumor type 1 interferon signaling, which incorporates work with human genetics and biosamples, will be instrumental in understanding how genes contribute to human health and disease.

From The Lab

Feb 24, 2017

First Immune Deficiency Foundation (IDF) Research Grant Awarded

Sep 22, 2016

LJI researcher receives Jeffrey Modell Foundation grant to study primary immunodeficiency

Jun 23, 2013

La Jolla Institute discovers new player critical to unleashing T cells against disease

Sharma Lab

Publications

PLoS Pathog

DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection

2018-07
Curr Opin Immunol

Cytosolic sensing of immuno-stimulatory DNA, the enemy within

2018-02
Nat Commun

Binding of NUFIP2 to roquin promotes recognition and regulation of ICOS mRNA

2018-01
Curr Opin Immunol

Cytosolic sensing of immuno-stimulatory DNA, the enemy within

2017-12
Dhanwani R, Takahashi M, Sharma S
J Virol

cGAS-STING signaling regulates initial innate control of cytomegalovirus infection

2016-08
Lio CJ, McDonald B, Takahashi M, Dhanwani R, Sharma N, Huang J, Pham E, Benedict CA, Sharma S
Gut

The TRAP1 ion channel is expressed in CD4+ T cells and restrains T-cell-mediated colitis through inhibition of TRPV1

2016-06
Bertin S, Aoki-Nonaka Y, Lee J, de Jong PR, Kim P, Han T, Yu T, To K, Takahashi N, Boland BS, Chang JT, Ho SB, Herdman…
Immunity

In vivo RNA interference screens identify regulators of antiviral CD4(+) and CD8(+) T cell differentiation

2014-08
Chen R, Bélanger S, Frederick MA, Li B, Johnston RJ, Xiao N, Liu YC, Sharma S, Peters B, Rao A, Crotty S, Pipkin ME
Nature

An siRNA screen for NFAT activation identifies septins as coordinators of store-operated Ca2+ entry

2013-07
Sharma S, Quintana A, Findlay GM, Mettlen M, Baust B, Jain M, Nilsson R, Rao A, Hogan PG

Principal Investigator

Sonia Sharma, Ph.D.

Assistant Professor, Director

Sonia Sharma Ph.D. is an Assistant Professor in the Division of Cell Biology, and Director of the RNAi Facility.

Dr. Sharma received her B.Sc. and Ph.D. in Microbiology and Immunology from McGill University, in Montréal, Québec. From 2004-2009, she was a Postdoctoral Fellow at the Immune Disease Institute (IDI) at Harvard Medical School in the laboratory of Dr. Anjana Rao. She was an instructor at IDI and in Pediatrics at Children’s Hospital Boston, and at Harvard Medical School.

Dr. Sharma joined La Jolla Institute as an Instructor in Developmental Immunology in 2011, and joined the faculty in July 2013.

Lab Members

Aitor Aguirre

Visiting Scientist

Quinn Bui

Intern

Emily Carron

Postdoctoral Fellow

Khoi Dao

Visiting Scientist

Rekha Dhanwani

Post-Doctoral Fellow

Biosketch:
I did my Ph.D from Defence Research and Development Establishment, India and joined University of Texas Medical Branch, Galveston as a visiting scientist in 2012. I joined University of Minnesota, Twin Cities, as a postdoctoral researcher in 2013 where my research focus was to develop a recombinant tri-segmented Pichinde virus as a novel live vaccine platform and use it as a protective tool against influenza infection in a mouse model. In 2015, I joined La Jolla Institute, San Diego where I am currently working as a Postdoctoral researcher.

Research Focus:
My research interests encompass numerous fields of virology with special emphasis on pathogenesis, antiviral research, vaccines and viral immunology.My current research projects are focused on the role of innate immunity in viral infections as well as in other inflammatory diseases including vasculopathies.

Career Goals:
I plan to pursue a career in scientific research focused on diseased animal models.

Kay Foos

Lab Assistant

Mariko Hara

Post-Doctoral Fellow

Biosketch:
I graduated from Tokyo University of Science in 2008 with a B.S. degree in Biological Science. I then obtained my Ph.D. in Life Science from the University of Tokyo in 2013. I began working as a postdoc in the Sharma laboratory at the La Jolla Institute for Immunology in August 2014.

Research Focus:
My research projects are focused on the roles of novel regulators in nucleic acid-sensing pathways. I am interested in understanding how the genes we have identified can regulate the STING pathway, and in clarifying the physiological roles in immune-mediated diseases and cancer.

Career Goals:

I plan to pursue a career in scientific research focused on innate immunity.

Kevin Lefever

Visiting Scientist

Ian Mathews

Graduate Student

Jeramie Watrous

Visiting Scientist

Sharma Lab

Research Projects

New molecular players in the cGAS-STING pathway of anti-viral and anti-tumor defense:

Cell-free, immuno-stimulatory DNA is recognized in the cytoplasm of cells as a universal danger signal by the innate immune system. We are using genome-scale RNAi and CRISPR/Cas9 approaches in primary human cells to identify important new players in the cGAS-STING pathway of innate cytoplasmic DNA sensing, which has been implicated as the primary sensor for many fungal, bacterial, viral pathogens, and even for neoplastic cells. We aniticpate that key regulators of this pathway will represent important targets for boosting innate immune responses to microbial pathogens and cancer.

Targeting tumor endothelium for cancer surveillance and immunotherapy:

Preliminary data from our lab shows that vascular endothelial cells (vECs) mount remarkably potent innate responses to cell-free DNA, which is well in accordance with their role as sentinels of the blood. However, little is known about how the contribution of innate endothelial responses to the inflammatory landscape of the tumor microenvironment. We are using primary endothelial-tumor cell co-culture, Next Generation RNA-sequencing profiling, RNAi/CRISPR/Cas9-mediated gene deletion, animal models of cancer and human tumor bio-samples to explore the role of vECs as bona fide effectors of the innate response to cancer.

Molecular mechanisms underlying novel interferonopathies:

In addition to their protective role against microbial pathogens and neoplastic cells, high levels of circulating type I Interferon are associated with the development of auto-immune diseases in humans. We have used a forward genetic approach to identify novel negative regulators of the innate response to cell-free DNA whose loss-of-function is known to be associated with systemic inflammation and auto-immunity. We are exploring the molecular mechanisms underlying the role of these negative regulators in type I Interferon signaling.