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## Overview

#### Earl Stadtman Investigator, NIH Distinguished Scholar

Luis M. Franco, M.D.

luis.franco@nih.gov

#### Research Areas (IRP Lab Groups)

Clinical Research

Computational Biology

Genetics and Genomics

Immunology

Systems Biology

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

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:

Image

### 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?

Image

### 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.

#### Related NIAMS Labs

                                    - Systemic Autoimmunity Branch
                                    - Lupus Clinical Trials Unit
                                    - Lupus Genomics and Global Health Disparities Unit

#### Partner Labs at NIH

                                    - NIEHS Molecular Endocrinology Group
                                    - NIA Transcription Systems Dynamics and Biology Unit
                                    - NIAID Signaling Systems Section
                                    - NCI High-Throughput Imaging Facility (HiTIF)
                                    - NCATS Early Translation Branch

#### Scientific Advances

July 1, 2022

Gene Expression Analysis in Single Cells Reveals Considerable Diversity in Human Neutrophils

February 17, 2022

A GMR-based Assay for Quantification of the Human Response to Influenza

#### Core Research Facilities

Labs at the NIAMS are supported by the following state-of-the-art facilities and services:
                                        - Biodata Mining and Discovery
                                        - Flow Cytometry
                                        - Genomic Technology
                                        - Laboratory Animal Care and Use
                                        - Light Imaging
                                        - Translational Immunology

## Staff

**Luis M. Franco, M.D.**

luis.franco@nih.gov

**Brinda Bhatt, Ph.D., M.S.**

brinda.bhatt@nih.gov

**Ariel Bohner, B.S.**

ariel.bohner@nih.gov

**Manasi Gadkari, M.S.**

manasi.gadkari@nih.gov

**Vishal Patel, B.S.**

vishal.patel3@nih.gov

*‌ *

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

                            - Robert Kwiat, B.S., 2021-2023
                            - 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

##### Visualizing Single RNA Molecules in Human Cells

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Robert Kwiat, a postbaccalaureate fellow in the Functional Immunogenomics Section at the NIAMS, discusses his work to visualize and study RNA within monocyte cells. Using advanced microscopy and other techniques, Robert explains how he identifies the location of RNA, its relevance, and how it informs further scientific study.

This research was conducted with the assistance of the NIAMS Light Imaging Section and utilized the Leica TCS SP8 X confocal microscope.

An audio described version of this video is also available.

##### 3D View of Human Monocytes

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This image was acquired using the Leica TCS SP8 X confocal scope, and applying a Z-stack acquisition modality to grab several focal planes along the Z-axis (to cover the entire volume of the cells). All focal planes were recomposed to create a 3D rendering of the cells and the image was exported and post-processed using the Imaris 9.7 image analysis software. The resulting image shows two monocytes, where nuclei (displaying the typical horseshoe shape) are depicted in violet and the plasma membrane in yellow with transparency.

Image acquired/processed by Robert Kwiat, Post-bac Fellow, Dr. Luis Franco’s Functional Immunogenomics Section, with assistance from Dr. Davide Randazzo, Chief, Light Imaging Section.

Download High Res(477.96 KB)

## Clinical Trials

## Scientific Publications

## Selected Recent Publications

###             hcHCR: High-Throughput Single-Cell Imaging of RNA in Human Primary Immune Cells.        

2784().

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

209(4).

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

28(9).

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

150(4).

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

6(13).

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

205().

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

68(2).

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

136(23).

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

117(28).

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

216(2).

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

5().

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

73(10).

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

132(6).

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

11(6).

## News & Highlights

NIAMS-Related Article | March 8, 2022

### New Web Application to Study Cellular Responses to Glucocorticoids

Read More

Announcement | August 19, 2020

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

Read More

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