Sarcoidosis program

Our research group interests are focused on discovery of mechanisms related to human diseases in response to microbial and environmental stressors.

We apply state-of-the-art tools including molecular and cell biology, metabolomics, and genetics to dissect the molecular mechanisms and to identify the determinant factor(s) related to human phenotypic diversity and clinical manifestation of diseases.

A - Regulation of the lung innate and adaptive immune responses

Research in my laboratory is focused on understanding the regulation of innate and adaptive immune responses to microbial antigens and environmental stressors. We are particularly interested to learn the role of human antigen-presenting cells in the modulation of B and T cell responses. As a pulmonologist, I have interest in granulomatous diseases that is why I built a research program focused on defining immune responses in various diffuse lung diseases such as including sarcoidosis. One of major focus in our lab is to study sarcoidosis that as a complex human disease involving many systems. I am interested in various type of immunity leading to phenotypic presentation of same diseases. My laboratory discovered that in sarcoidosis there is a lack of negative regulation through lack of expression of specific phosphatases (such as MKP-1). As there are no animal models available for this disease, my laboratory developed a systematic approach using in- vitro bronchoalveolar lavage cells (BALs), alveolar macrophages as well as peripheral blood mononuclear cells of sarcoidosis patients to study signaling pathways in this disease. Our novel data obtained by RNA sequencing from monocytes and alveolar macrophages from sarcoidosis subjects as well as healthy controls showed large number of differentially expressed genes in sarcoidosis. We identified critical roles of uncontrolled p38 activation to sustained inflammatory responses in sarcoidosis. Importantly, we showed recently that there is an aberrant expression for HIF-1α in sarcoidosis macrophages and granulomatous tissues. This aberrant expression was coupled with increased IL-1β and IL-17 in sarcoidosis.

Related publications:

1. Jaya Talreja*, Harvinder Talwar, Christian Bauerfeld*, Grossman LI, Zhang K, Tranchida P, and Lobelia Samavati. MEK2 negatively. HIF-1α regulates IL-1β and IL-17 in sarcoidosis. Elife. 2019 Apr 4;8. pii: e44519. doi: 10.7554/eLife.44519 Impact Factor: 7.8 ;Citations: Citation:23
2. Jaya Talreja, Christian Bauerfeld, Edward Sendler, Roger Pique-Regi, Francesca Luca and Samavati L Derangement of Metabolic and Lysosomal Gene Profiles in Response to Dexamethasone Treatment in Sarcoidosis. Frontiers Immunology, Front Immunol. 2020 May 12;11:779. doi: 10.3389/fimmu.2020.00779
3. Rastogi R, Jiang Z, Ahmad N, Rosati R, Liu Y, Beuret L, Monks R, Charron J, Birnbaum MJ, Samavati L. Rapamycin induces mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) expression through activation of protein kinase B and mitogen-activated protein kinase kinase pathways. J Biol Chem. 2013 Nov 22;288(47):33966-77.
4. Jaya Talreja*, Harvinder Talwar, Nisar Ahmad, Ruchi Rastogi, and L. Samavati. Dual Inhibition of Rip2 and IRAK1/4 Regulates IL-1β and IL-6 in Sarcoidosis Alveolar Macrophages and Peripheral Blood Mononuclear Cells. J Immunol. 2016 Aug 15;197(4):1368-78. doi: 10.4049/jimmunol.1600258

B - Technology development to identify disease specific immunoglobulins

One of our goal in the research is to identify and validate a panel of biomarkers in form of immunoglobulin, especially IgG for various diseases, including sarcoidosis and tuberculosis. Additionally, we aim to identify the clinical values of identified IgG in predicting stages and outcome of sarcoidosis. Our lab developed a novel antigen library derived from human lung cells supported by various grants by the National Heart, Lungs, and Blood Institute (NHLBI). For this purpose, we constructed a T7 phage cDNA library of potential sarcoidosis antigens using mRNA isolated from BALs and WBCs of sarcoid patients. This cDNA library was immunoscreened with sera from patients with sarcoidosis and healthy subjects and patients with tuberculosis (TB). Additionally, we used sera from smear positive TB subjects and as negative controls we used sera from healthy subjects, cystic fibrosis and lung cancer. We identified biomarkers with high specificity and sensitivity which can classify TB from cystic fibrosis.

Related publications:

1. Jaya Talreja, Changya Peng, Kezhong Zhang, Lobelia Samavati- Novel Sarcoidosis Epitope Augments MHCII, CD80/CD86 Expression, Promotes B-Cell Differentiation and IgG Production. Am J Respir Cell Mol Biol. 2025 Jan 21. doi: 10.1165/rcmb.2024-0428OC. PMID: 39836049
2. Lobelia Samavati, Jaya Talreja, Changya Peng, Sarcoidosis Immunodiagnostic Detects IgG Antibodies Against Unique Antigenic Epitopes. AJRCCM; PMID: 39078236 DOI: 10.1164/rccm.202406-1235LE
3. Changya Peng, Jaya Talreja, Brennen Steinbauer, Laura Koth, Lobelia Samavati; Discovery of Two Novel Immunoepitopes and Development of a Peptide-based Sarcoidosis Immunoassay. AJRCCM: PMID: 38299032; Citation:7
4. Jaya Talreja, Changya Peng, Lobelia Samavati; MIF modulates p38/ERK phosphorylation via MKP-1 induction in sarcoidosis; IScience 2023 Dec 14;27(1):108746. doi: 10.1016/j.isci.2023.108746. PMID: 38299032; Citation:1
5. Jaya Talreja, Changya Peng, Tuan-Minh Nguyen, Sorin Draghici, Lobelia Samavati. Discovery of Novel Transketolase Epitopes and the Development of IgG-Based Tuberculosis Serodiagnostics. Microbiology Spectrum: DOI: doi.org/10.1128/spectrum.03377-22. Pubmed ID: PMID: 30029479. Citation:Samer Najeeb Hanoudi, Harvinder Talwar, Sorin Draghici and Lobelia Samavati. Autoantibodies against cytoskeletons and lysosomal trafficking discriminate sarcoidosis from healthy controls, tuberculosis and lung cancers. Molecular Biomedicine (2022-01-20).
6. Talwar H, Hanoudi SN, Draghici S and Samavati L. Novel T7 Phage Display Library Detects Classifiers for Active Mycobacterium Tuberculosis Infection. Viruses. 2018 Jul 19;10(7). pii: E375. doi: 10.3390/v10070375.

C - Mouse Model: Adjacent to directly human related research, our laboratory is interested to uncover the mechanisms of sustained versus resolution of inflammation in murine models.

We are interested in various posttranslational modifications of proteins, such as phosphorylation, ubiquitination and their effect on the gene transcription factors, signal transduction that modulate cellular responses and cellular bioenergetics.

Related Publications:

1. Talreja J, Bauerfeld C, Wang X, Hafner M, Liu Y, Samavati L. MKP-1 modulates ubiquitination/phosphorylation of TLR signaling. Life Sci Alliance. 2021 Sep 27;4(12):e202101137. doi: 10.26508/lsa.202101137. Print 2021 Dec. PMID: 34580177
2. Harvinder Talwar, Mohamad Bouhamdan, Christian Bauerfeld*, Jaya Talreja*, Rifdat Aoidi, Nicolas Houde, Jean Charron, and Lobelia Samavati. MEK2 negatively Regulates LPS Mediated IL-1βProduction Through HIF-1α Expression. Journal of immunology. 2019 Feb 1. pii: ji1801477. doi: 10.4049/jimmunol.1801477 Impact Factor: 5.2 Citations:7
3. Jaya Talreja* and Samavati L. K63-Linked Polyubiquitination on TRAF6 Regulates LPS-Mediated MAPK Activation, Cytokine Production, and Bacterial Clearance in Toll-Like Receptor 7/8 Primed Murine Macrophages. Front Immunol. 2018 Feb 21;9:279. doi: 10.3389/fimmu.2018.00279.
4. Kezhong Zhang; HuiLiu, Zhenfeng Song,Yuan yuan Jiang, HyunbaeKim, Lobelia Samavati, Hien M.Nguyen, Zeng-QuanYang. The UPR Transducer IRE1 Promotes Breast Cancer Malignancy by Degrading Tumor Suppressor microRNAs; iScience. 2020 Aug 25;23(9):101503. doi: 10.1016/j.isci.2020.101503. Online ahead of print.PMID: 32911332
5. Samavati L, Lee I, Mathes I, Lottspeich F, and Hüttemann M. TNFα Inhibits Oxidative Phosphorylation through Tyrosine Phosphorylation at Subunit I of Cytochrome c Oxidase. J Biol Chem 2008; 283:21134-44.

D - Clinical Research

Related publications:

1. Samavati, L and Bruce Uhal ACE2, MUCH MORE THAN JUST A RECEPTOR FOR SARS-COV-2. Frontiers in Cellular and Infection Microbiology, 2020 Jun 5;10:317. doi: 10.3389/fcimb.2020.00317
2. Muhanad Taha, Dahlia Sano, Samer Hanoudi, Zahia Esber, Morvarid Elahi, Ali Gabali, Teena Chopra, Sorin Draghici and Lobelia Samavati; Platelets and renal failure in the SARS-CoV-2 syndrome; Platelets;
3. Muhanad Taha and Lobelia Samavati; Antiphospholipid antibodies in COVID-19: a meta-analysis and systematic review. RMD Open. 2021 May;7(2):e001580. doi: 10.1136/rmdopen-2021-001580.PMID: 33958439;
4. Bourbonnais J M and Samavati L. Clinical predictors of pulmonary hypertension in sarcoidosis. Eur Respir J 2008;32:296-302.

Complete list of publications