The Genomic Research Laboratory for Lung Fibrosis, Dr. Avraham (Rami) Unterman >>

The Genomic Research Laboratory for Lung Fibrosis

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Our Vision

To uncover the basic mechanisms underlying lung fibrosis and develop new treatments - Interstitital lung diseases (ILDs) consist of over 200 different diseases. Many patients, in particular those who are diagnosed with idiopathic pulmonary fibrosis (IPF), develop severe lung scarring (called lung fibrosis) that necessitates lung transplantation for survival, including some who recover from COVID-19. Despite multidisciplinary approaches to diagnose ILD patients, in many cases the exact diagnosis is unclear. Furthermore, current treatment options may delay disease progression but cannot provide cure. In our laboratory, we employ cutting-edge genomic technologies, including single cell RNA sequencing (scRNA-seq), to study ILD patient-derived samples. We believe that by using scRNA-seq, we may come one step closer towards elucidating the biology of these intricate diseases, identify new biomarkers and develop novel treatments for ILD patients.

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Contact Us

Primary Investigators
Dr Unterman PI Small picture

Dr. Avraham (Rami) Unterman, MD, MBA, Lab PI

03-697‏2552‏ ramiu@tlvmc.gov.il

Dr Stein Lab Manager small pic

Yan Stein, PhD, Lab manager

03-697‏2552‏ yanst@tlvmc.gov.il

General Contact
Address

Sammy Ofer Heart ‎ Building

10th floor Room 64-65

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Research

Characterizing the Immune Dysregulation in COVID-19 patients

COVID-19 may manifest itself as a mild to moderate disease, or as a severe disease requiring intensive care unit (ICU)-level care that may include mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Evidence suggest that dysregulated inflammation plays an important role in the exacerbation of the disease, which may lead to an increased morbidity and mortality of the disease. Nonetheless, the exact molecular mechanisms accounting for this immune dysregulation, as well as their modulation during different stages of the disease, are not fully characterized. In a joined effort together with five different laboratories in Yale School of Medicine, we performed an in-depth, single-cell multi-omics analysis of immune cells that were derived from progressive and stable COVID-19 patients. This analysis revealed unique cell populations of both the innate and adaptive immune cells, as well as aberrant cell-cell interactions between them, that characterized progressive COVID-19 patients. In addition, unique profiling of T cells and B cells revealed a skewed expansion of specific clones that characterized progressive patients. To conclude, this study revealed a dyssynchrony of the innate and adaptive immune system in progressive COVID-19 patients. This study is currently under revision in Nature Communications journal (see publications section).

Immune landscape of Chronic Fibrosing Interstitial Lung Diseases (ILDs)

Among of the most common ILDs are idiopathic lung fibrosis (IPF), chronic hypersensitivity pneumonitis (CHP) and connective tissue-related ILDs (CTD-ILDs). It is important to differentiate between these diagnoses, since CHP and CTD-ILD require immunosuppressive therapies, while IPF is exacerbated by this treatment regime and require anti-fibrotic agents instead. We wish to analyze immune cells, which can be easily extracted from patients’ blood, by utilizing scRNA-seq. This analysis will facilitate the identification of immunological mechanisms that drive these diseases and allow the development of precision medicine approaches for diagnosis and treatment

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly worldwide. Neovascular AMD (nAMD) is a severe AMD subtype that emerges abruptly and may cause a rapid deterioration in vision, eventually leading to blindness if left untreated. Though treatment for nAMD is available, it fails in approximately one third of the patients due to the development of macular fibrosis or atrophy. Currently, the mechanisms underlying macular fibrosis are poorly understood. By usingmulti-omics approach, we wish to characterize the mechanisms underlying nAMD and macular fibrosis. . The identification of such mechanisms is expected to facilitate the devising of new therapeutic approaches to nAMD patients that developed macular fibrosis, for which therapeutic approaches are currently unavailable.

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Our Team

Current Staff

Researchers

Clinical Research Coordinator

Current funding

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Highlight Publications


. Single-Cell Omics Reveals Dyssynchrony of the Innate and Adaptive Immune System in Progressive COVID-19 Unterman A, Sumida TS, Nouri N, Yan X, Zhao A, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C Jr., Deng W, Chen M, Raredon S, Hoehn K, Wang G, Wang Z, DeIuliis G, Ravindra N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels C, Wyllie A, Grubaugh N, Melillo A, Meng H, the Yale IMPACT research team, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler DA, Kaminski N, Dela Cruz CS
MedRxiv 2020 (pre-print) Under revision in Nature Communications

Blood Transcriptomic Predicts Progression of Pulmonary Fibrosis and Associates Natural Killer Cells. SHuang Y, Oldham JM, Ma SF, Unterman A, Liao SY, Barros AJ, Bonham CA, Kim JS, Vij R, Adegunsoye A, Strek ME, Molyneaux PL, Maher TM, Herazo-Maya JD, Kaminski N, Moore BB, Martinez FJ, Noth I.
Am J Respir Crit Care Med 2021 (In Press).

Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, Lucas CL
Immunity 2021; 54(5):1083-1095.e7.

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. Cutting Edge: Distinct B Cell Repertoires Characterize Patients with Mild and Severe COVID-19 Hoehn KB, Ramanathan P, Unterman A, Sumida TS, Asashima H, Hafler DA, Kaminski N, Dela Cruz CS, Sealfon SC, Bukreyev A, Kleinstein SH
J Immunol 2021;206(12):2785-2790.

. Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells Sumida TS, Dulberg S, Schupp J, Stillwell HA, Axisa PP, Comi M, Lincoln M, Unterman A, Kaminski N, Madi A, Kuchroo VK, Hafler DA
BioRxiv 2020 (pre-print). Under review in Nature Immunology

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