Overview

Earl Stadtman Investigator, NIH Distinguished Scholar

The Functional Immunogenomics Section (FIS) studies how genes control the function of cells in the human immune system. We are especially interested in how treatments that change the expression of human genes affect the behavior of immune cells. Our long-term goal is to enable the development of better treatments for human diseases that are caused by an overactive immune system.

FIS scientists work at the intersection of clinical medicine, human immunology, genomics, and bioinformatics. A major area of focus for our team is the dissection of the mechanisms by which glucocorticoids regulate human immunity. Glucocorticoids are a class of drugs. They have been the cornerstone of anti-inflammatory and immunosuppressive therapies for over 70 years. They are highly effective at controlling an overactive immune system, but they also have a long list of serious side effects. Although they are one of the most widely prescribed classes of drugs worldwide, there are surprisingly large gaps in our understanding of how glucocorticoids regulate the behavior of human immune cells. Our team is working to help fill in those gaps, by applying advanced genomic and proteomic technologies to the study of the response to glucocorticoids in healthy humans and people with autoimmune diseases.

Our Research Platform

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Diagram: our research platform, aimed at understanding how glucocorticoids work
The FIS’s research platform combines in vivo and in vitro studies in human cells and tissues, and applies cutting-edge genomic and proteomic technologies to improve our understanding of how drugs affect the immune system and to develop safer therapies for patients with autoimmune and inflammatory conditions.

The FIS’s research platform combines clinical studies in patients with autoimmune diseases and healthy volunteers, with laboratory studies of human cells and tissues. Cutting-edge genomic and proteomic technologies are employed to identify the key genes and proteins that are responsible for the functional effects of glucocorticoids in human cells. In collaboration with the National Center for Advancing Translational Sciences (NCATS), we then work to translate the findings of our research into therapies that can mimic the clinically beneficial effects of glucocorticoids but have fewer side effects.

Bioinformatics Tools

Web applications developed by our lab:

GCgx - How do glucocorticoids work?

GCgx is a scientific web application that allows scientists to study the response of different cell types to glucocorticoids. It provides a simple, mobile-friendly tool that can offer quick answers to the following questions: Is my gene of interest responsive to glucocorticoids in specific cell types? If so, how does its level of expression vary over time and how statistically significant is the change?

NeutGX - Explore the neutrophil transcriptome

NeutGX is a web application that allows investigators to explore the transcriptome of human neutrophils. This tool is available as part of a suite of NIAID Bioinformatics Applications.

Staff

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Seven members of the lab seated eating a meal.
Earl Stadtman Investigator, NIH Distinguished Scholar
Postdoctoral Fellow
Special Volunteer
Senior Research Associate
Postbaccalaureate Fellow
Postbaccalaureate Fellow
‌ 

Our lab is always seeking to recruit the best talent in the scientific community. If you are interested in joining our team, please contact us.

Former Lab Members

Postbaccalaureate Students

  • Qilin Cao, B.S., 2019-2022
  • Thai Tran, B.S., 2019-2021

Rotating Medical/Graduate Students

  • John Michael Sanchez, M.D. Ph.D. Student, 2021

Image & Media Gallery

Clinical Trials

RECRUITING

Genomic Responses of Human Immune and Non-Immune Cells to Glucocorticoids

ClinicalTrials.gov Identifier: NCT02798523

The immune system defends the body against bacteria and other harmful invaders. But it can overact and attack healthy cells by mistake. The group of drugs called glucocorticoids (GCs) can calm down an overactive immune system. But they often cause negative side effects. Researchers want to learn how human genes respond to GCs. Genes live inside each cell of the body. They tell our cells how to function. Researchers hope the results of this study will show them how to develop better drugs that will have the benefits of GCs without the side effects.


RECRUITING

Genomic Effects of Glucocorticoids in Patients With Systemic Lupus Erythematosus

ClinicalTrials.gov Identifier: NCT04233164

The immune system is the body's defense against bacteria and other harmful invaders. In people with systemic lupus erythematosus (SLE), the immune system becomes overactive and attacks healthy cells by mistake. Many people use glucocorticoids (GCs) to treat their SLE. GCs can calm down an overactive immune system by changing how the body reads genes. But GCs have side effects that can increase over time. Researchers want to learn more about how GCs work. This may help to develop new and better drugs for treating SLE without the side effects GCs have.


Scientific Publications

Selected Recent Publications

Single-Cell Analysis Reveals the Range of Transcriptional States of Circulating Human Neutrophils.

Wigerblad G, Cao Q, Brooks S, Naz F, Gadkari M, Jiang K, Gupta S, O'Neil L, Dell'Orso S, Kaplan MJ, Franco LM
J Immunol.
2022 Aug 15;
209(4).
doi: 10.4049/jimmunol.2200154
PMID: 35858733

High-throughput imaging of mRNA at the single-cell level in human primary immune cells.

Gadkari M, Sun J, Carcamo A, Alessi H, Hu Z, Fraser IDC, Pegoraro G, Franco LM
RNA.
2022 Sep;
28(9).
doi: 10.1261/rna.079239.122
PMID: 35764396

Clinical exome sequencing of 1000 families with complex immune phenotypes: Toward comprehensive genomic evaluations.

Similuk MN, Yan J, Ghosh R, Oler AJ, Franco LM, Setzer MR, Kamen M, Jodarski C, DiMaggio T, Davis J, Gore R, Jamal L, Borges A, Gentile N, Niemela J, Lowe C, Jevtich K, Yu Y, Hullfish H, Hsu AP, Hong C, Littel P, Seifert BA, Milner J, Johnston JJ, Cheng X, Li Z, Veltri D, Huang K, Kaladi K, Barnett J, Zhang L, Vlasenko N, Fan Y, Karlins E, Ganakammal SR, Gilmore R, Tran E, Yun A, Mackey J, Yazhuk S, Lack J, Kuram V, Cao W, Huse S, Frank K, Fahle G, Rosenzweig S, Su Y, Hwang S, Bi W, Bennett J, Myles IA, De Ravin SS, Fuss I, Strober W, Bielekova B, Almeida de Jesus A, Goldbach-Mansky R, Williamson P, Kumar K, Dempsy C, Frischmeyer-Guerrerio P, Fisch R, Bolan H, Metcalfe DD, Komarow H, Carter M, Druey KM, Sereti I, Dropulic L, Klion AD, Khoury P, O' Connell EM, Holland-Thomas NC, Brown T, McDermott DH, Murphy PM, Bundy V, Keller MD, Peng C, Kim H, Norman S, Delmonte OM, Kang E, Su HC, Malech H, Freeman A, Zerbe C, Uzel G, Bergerson JRE, Rao VK, Olivier KN, Lyons JJ, Lisco A, Cohen JI, Lionakis MS, Biesecker LG, Xirasagar S, Notarangelo LD, Holland SM, Walkiewicz MA
J Allergy Clin Immunol.
2022 Oct;
150(4).
doi: 10.1016/j.jaci.2022.06.009
PMID: 35753512

The contribution of rare copy number variants in FAS toward pathogenesis of autoimmune lymphoproliferative syndrome.

Jevtich K, Price S, Similuk M, Kulm E, Yan J, Setzer M, Jamal L, Franco LM, Ghosh R, Walkiewicz M, Rao VK
Blood Adv.
2022 Jul 12;
6(13).
doi: 10.1182/bloodadvances.2021005835
PMID: 35476126

A GMR-based assay for quantification of the human response to influenza.

Ravi N, Chang SE, Franco LM, Nagamani SCS, Khatri P, Utz PJ, Wang SX
Biosens Bioelectron.
2022 Jun 1;
205().
doi: 10.1016/j.bios.2022.114086
PMID: 35192997

GCgx: transcriptome-wide exploration of the response to glucocorticoids.

Cao Q, Boo Irizarry Y, Yazhuk S, Tran T, Gadkari M, Franco LM
J Mol Endocrinol.
2021 Dec 10;
68(2).
doi: 10.1530/JME-21-0107
PMID: 34787097

Glucocorticoid-induced eosinopenia results from CXCR4-dependent bone marrow migration.

Hong SG, Sato N, Legrand F, Gadkari M, Makiya M, Stokes K, Howe KN, Yu SJ, Linde NS, Clevenger RR, Hunt T, Hu Z, Choyke PL, Dunbar CE, Klion AD, Franco LM
Blood.
2020 Dec 3;
136(23).
doi: 10.1182/blood.2020005161
PMID: 32659786

Sex differences in neutrophil biology modulate response to type I interferons and immunometabolism.

Gupta S, Nakabo S, Blanco LP, O'Neil LJ, Wigerblad G, Goel RR, Mistry P, Jiang K, Carmona-Rivera C, Chan DW, Wang X, Pedersen HL, Gadkari M, Howe KN, Naz F, Dell'Orso S, Hasni SA, Dempsey C, Buscetta A, Frischmeyer-Guerrerio PA, Kruszka P, Muenke M, Franco LM, Sun HW, Kaplan MJ
Proc Natl Acad Sci U S A.
2020 Jul 14;
117(28).
doi: 10.1073/pnas.2003603117
PMID: 32601182

Immune regulation by glucocorticoids can be linked to cell type-dependent transcriptional responses.

Franco LM, Gadkari M, Howe KN, Sun J, Kardava L, Kumar P, Kumari S, Hu Z, Fraser IDC, Moir S, Tsang JS, Germain RN
J Exp Med.
2019 Feb 4;
216(2).
doi: 10.1084/jem.20180595
PMID: 30674564

Transcript- and protein-level analyses of the response of human eosinophils to glucocorticoids.

Gadkari M, Makiya MA, Legrand F, Stokes K, Brown T, Howe K, Khoury P, Hu Z, Klion A, Franco LM
Sci Data.
2018 Dec 4;
5().
doi: 10.1038/sdata.2018.275
PMID: 30512017

Glucocorticoid-induced eosinopenia in humans can be linked to early transcriptional events.

Khoury P, Stokes K, Gadkari M, Makiya MA, Legrand F, Hu Z, Klion A, Franco LM
Allergy.
2018 Oct;
73(10).
doi: 10.1111/all.13497
PMID: 29885264

Syndromic congenital myelofibrosis associated with a loss-of-function variant in RBSN.

Magoulas PL, Shchelochkov OA, Bainbridge MN, Ben-Shachar S, Yatsenko S, Potocki L, Lewis RA, Searby C, Marcogliese AN, Elghetany MT, Zapata G, Hernández PP, Gadkari M, Einhaus D, Muzny DM, Gibbs RA, Bertuch AA, Scott DA, Corvera S, Franco LM
Blood.
2018 Aug 9;
132(6).
doi: 10.1182/blood-2017-12-824433
PMID: 29784638

Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections--A Prospective Cohort Study.

Zhai Y, Franco LM, Atmar RL, Quarles JM, Arden N, Bucasas KL, Wells JM, Niño D, Wang X, Zapata GE, Shaw CA, Belmont JW, Couch RB
PLoS Pathog.
2015 Jun;
11(6).
doi: 10.1371/journal.ppat.1004869
PMID: 26070066

News & Highlights

NIAMS-Related Article | March 8, 2022

New Web Application to Study Cellular Responses to Glucocorticoids

Although the drugs have been around for more than 70 years, scientists have a poor understanding of how glucocorticoids regulate the immune system and the mechanisms by which they cause toxicity in different organs.
Announcement | August 19, 2020

NIH Offers Web-Based Tool to Study Gene Expression in Human Neutrophils

NIH scientists developed and recently released a free, online data query tool called NeutGX. Researchers around the world can use NeutGX to explore the genetic basis of neutrophil-mediated inflammation in autoimmune diseases, cancer, infectious diseases and other conditions.