Major Areas of Research
- Translational genomics
- Functional genomics of the human response to glucocorticoids
- Integrative genomic analysis of the human response to vaccines and viral infections
- Influence of human genetic variation on immune responses
- Human genetics
My laboratory seeks to employ the tools of modern functional genomic analysis in the solution of problems that are directly relevant to human health.
Functional genomics of glucocorticoid action: Glucocorticoids are among the most frequently prescribed immunosuppressive and anti-inflammatory medications worldwide. Long-term use, however, is complicated by serious non-immunologic side effects. A large gap of knowledge about the differences between the actions of this class of drugs on immune and non-immune cells has prevented the development of more targeted therapies or the use of drug combinations that would preserve the desired immunological effects while ameliorating unwanted systemic activities. Glucocorticoids are ligands for a nuclear receptor, and their mechanism of action involves broad effects on gene expression via binding to the mammalian glucocorticoid response element (GRE). Recent discoveries, including that of a negative GRE and of a glucocorticoid-responsive long non-coding RNA (lncRNA), suggest that other important aspects of drug action at the genome level remain incompletely characterized. We are currently working to dissect carefully the transcriptional response of the human genome (including coding and non-coding elements) to glucocorticoids and to compare the responses of individual cell sub-populations. These studies involve both in vitro and in vivo experiments, ranging from cultured cells to clinical experiments with human volunteers at the National Institutes of Health Clinical Center.
Integrative genomic analysis of the human response to vaccines and viral infections: Identification of the host genetic factors that contribute to variation in the human response to vaccines and infections may uncover important mechanisms affecting the effectiveness of immune responses. We have been involved in the description of the transcriptional response to naturally acquired influenza virus infection in a human cohort and are currently working in collaboration with Dr. John Tsang’s laboratory to understand how infection affects the way in which each of the two copies of a gene is independently expressed.
Dr. Franco received his M.D. from the Javeriana University School of Medicine in Bogotá, Colombia, in 2000. He completed a residency in internal medicine and a fellowship in clinical genetics at Baylor College of Medicine in Houston. From 2009 to 2014, he was assistant professor in the department of molecular and human genetics and the department of medicine at Baylor College of Medicine. He joined the Laboratory of Systems Biology as an assistant clinical investigator in 2014. As a physician-scientist, he is interested in the application of systems biology methods to the solution of clinically important problems and to the study of traits that directly relate to human health.
Manasi Gadkari, M.Sc., Research Associate
Katherine Howe, PA-C, MPH [C], Clinical Study Coordinator
Integrative genomic analysis of human immune 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. Immune regulation by glucocorticoids can be linked to cell type-dependent transcriptional responses. J Exp Med. 2019 Feb 4;216(2):384-406. Note: See the Research Highlight on this piece in Nature Reviews Rheumatology and the Faculty Member Recommendation on F1000Prime.
Khoury P, Stokes K, Gadkari M, Makiya MA, Legrand F, Hu Z, Klion A, Franco LM. Glucocorticoid-induced eosinopenia in humans can be linked to early transcriptional events. Allergy. 2018 Oct;73(10):2076-2079.
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. Host transcriptional response to influenza and other acute respiratory viral infections--a prospective cohort study. PLoS Pathog. 2015 Jun 12;11(6):e1004869.
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. Syndromic congenital myelofibrosis associated with a loss-of-function variant in RBSN. Blood. 2018 Aug 9;132(6):658-662. Note: See the commentary on this piece in Blood.
Drummond RA, Franco LM, Lionakis MS. Human CARD9: A Critical Molecule of Fungal Immune Surveillance. Front Immunol. 2018 Aug 6;9:1836.
Karaca E, Weitzer S, Pehlivan D, Shiraishi H, Gogakos T, Hanada T, Jhangiani SN, Wiszniewski W, Withers M, Campbell IM, Erdin S, Isikay S, Franco LM, Gonzaga-Jauregui C, Gambin T, Gelowani V, Hunter JV, Yesil G, Koparir E, Yilmaz S, Brown M, Briskin D, Hafner M, Morozov P, Farazi TA, Bernreuther C, Glatzel M, Trattnig S, Friske J, Kronnerwetter C, Bainbridge MN, Gezdirici A, Seven M, Muzny DM, Boerwinkle E, Ozen M; Baylor Hopkins Center for Mendelian Genomics, Clausen T, Tuschl T, Yuksel A, Hess A, Gibbs RA, Martinez J, Penninger JM, Lupski JR. Human CLP1 mutations alter tRNA biogenesis, affecting both peripheral and central nervous system function. Cell. 2014 Apr 24;157(3):636-50.