Our Research
![Microscope image of lung tissue samples](https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_200_16_9/public/media/images/2023-04/image009.png?itok=VLF3WMXl 200w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_260_16_9/public/media/images/2023-04/image009.png?itok=W4Pie0Wa 260w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_320_16_9/public/media/images/2023-04/image009.png?itok=SU35G34o 320w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_400_16_9/public/media/images/2023-04/image009.png?itok=tMwKc_ZI 400w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_520_16_9/public/media/images/2023-04/image009.png?itok=ipB9GNsu 520w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_640_16_9/public/media/images/2023-04/image009.png?itok=5Mti_xeh 640w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_800_16_9/public/media/images/2023-04/image009.png?itok=3oCGLRh5 800w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1040_16_9/public/media/images/2023-04/image009.png?itok=anfmFOHg 1040w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1280_16_9/public/media/images/2023-04/image009.png?itok=VQqlBTzi 1280w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1600_16_9/public/media/images/2023-04/image009.png?itok=adcFSohE 1600w)
Investigating the Genetic Basis of Monogenic Adult-Onset Lung Fibrosis
The Garcia Lab investigates the genetic basis of monogenic adult-onset lung fibrosis. We have partnered with familial pulmonary fibrosis (FPF) kindreds and individuals with idiopathic pulmonary fibrosis (IPF) to investigate the genetic underpinnings of adult-onset disease. We have identified rare variants in genes belonging to the surfactant (SFTPA2), telomerase (TERT, TERC, RTEL1, PARN) and mitotic spindle (KIF15) pathways. Each of the disease variants is individually rare and typically private for the family in which it is discovered. However, collectively, rare coding variants are found in ~25% of all FPF kindreds and ~5% of IPF patients.
Adult-Onset Pulmonary Fibrosis Caused by Mutations in Telomerase
![Adult-onset pulmonary fibrosis caused by mutations in telomerase](https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_200/public/media/general/2023-05/adult-onset_pulmonary_fibrosis_caused_by_mutations_in_telomerase.jpg?itok=uFRxMioG 200w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_260/public/media/general/2023-05/adult-onset_pulmonary_fibrosis_caused_by_mutations_in_telomerase.jpg?itok=jbm65N9q 260w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_320/public/media/general/2023-05/adult-onset_pulmonary_fibrosis_caused_by_mutations_in_telomerase.jpg?itok=n4JqLH3M 320w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_400/public/media/general/2023-05/adult-onset_pulmonary_fibrosis_caused_by_mutations_in_telomerase.jpg?itok=v_Ofga2y 400w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_520/public/media/general/2023-05/adult-onset_pulmonary_fibrosis_caused_by_mutations_in_telomerase.jpg?itok=uNhSqiE8 520w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_640/public/media/general/2023-05/adult-onset_pulmonary_fibrosis_caused_by_mutations_in_telomerase.jpg?itok=KDtlYb_V 640w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_800/public/media/general/2023-05/adult-onset_pulmonary_fibrosis_caused_by_mutations_in_telomerase.jpg?itok=gAPMhfm2 800w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1040/public/media/general/2023-05/adult-onset_pulmonary_fibrosis_caused_by_mutations_in_telomerase.jpg?itok=d24oBIy4 1040w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1600/public/media/general/2023-05/adult-onset_pulmonary_fibrosis_caused_by_mutations_in_telomerase.jpg?itok=6KNF_yNZ 1200w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1280/public/media/general/2023-05/adult-onset_pulmonary_fibrosis_caused_by_mutations_in_telomerase.jpg?itok=dZvyvx-A 1280w)
Proc Natl Acad Sci USA. 2007.
Genetic Defects in Surfactant Protein A2 Associated with Pulmonary Fibrosis and Lung Cancer
![Genetic defects in surfactant protein A2 associated with pulmonary fibrosis and lung cancer](https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_200/public/media/general/2023-05/genetic_defects_in_surfactant_protein_a2_associated_with_pulmonary_fibrosis_and_lung_cancer.jpg?itok=I6syQzZd 200w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_260/public/media/general/2023-05/genetic_defects_in_surfactant_protein_a2_associated_with_pulmonary_fibrosis_and_lung_cancer.jpg?itok=3zmQb-7E 260w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_320/public/media/general/2023-05/genetic_defects_in_surfactant_protein_a2_associated_with_pulmonary_fibrosis_and_lung_cancer.jpg?itok=_gVYStAm 320w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_400/public/media/general/2023-05/genetic_defects_in_surfactant_protein_a2_associated_with_pulmonary_fibrosis_and_lung_cancer.jpg?itok=3D50ocCq 400w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_520/public/media/general/2023-05/genetic_defects_in_surfactant_protein_a2_associated_with_pulmonary_fibrosis_and_lung_cancer.jpg?itok=QvunwyY3 520w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_640/public/media/general/2023-05/genetic_defects_in_surfactant_protein_a2_associated_with_pulmonary_fibrosis_and_lung_cancer.jpg?itok=nhHO39qb 640w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_800/public/media/general/2023-05/genetic_defects_in_surfactant_protein_a2_associated_with_pulmonary_fibrosis_and_lung_cancer.jpg?itok=sle2H7Zi 800w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1040/public/media/general/2023-05/genetic_defects_in_surfactant_protein_a2_associated_with_pulmonary_fibrosis_and_lung_cancer.jpg?itok=m10RoeuF 1040w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1600/public/media/general/2023-05/genetic_defects_in_surfactant_protein_a2_associated_with_pulmonary_fibrosis_and_lung_cancer.jpg?itok=NczC0N0O 1200w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1280/public/media/general/2023-05/genetic_defects_in_surfactant_protein_a2_associated_with_pulmonary_fibrosis_and_lung_cancer.jpg?itok=tNqq7mGt 1280w)
Am J Hum Genet. 2009.
Exome Sequencing Links Mutations in PARN and RTEL1 with Familial Pulmonary Fibrosis and Telomere Shortening
![Exome Sequencing Links Mutations in PARN and RTEL1 with Familial Pulmonary Fibrosis and Telomere Shortening](https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_200/public/media/general/2023-05/exome_sequencing_links_mutations_in_parn_and_rtel1_with_familial_pulmonary_fibrosis_and_telomere_shortening.jpg?itok=c1iPrmD6 200w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_260/public/media/general/2023-05/exome_sequencing_links_mutations_in_parn_and_rtel1_with_familial_pulmonary_fibrosis_and_telomere_shortening.jpg?itok=S-Hv4asN 260w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_320/public/media/general/2023-05/exome_sequencing_links_mutations_in_parn_and_rtel1_with_familial_pulmonary_fibrosis_and_telomere_shortening.jpg?itok=FUmPoGn2 320w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_400/public/media/general/2023-05/exome_sequencing_links_mutations_in_parn_and_rtel1_with_familial_pulmonary_fibrosis_and_telomere_shortening.jpg?itok=ZngsxIyX 400w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_520/public/media/general/2023-05/exome_sequencing_links_mutations_in_parn_and_rtel1_with_familial_pulmonary_fibrosis_and_telomere_shortening.jpg?itok=onHK_qDb 520w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_640/public/media/general/2023-05/exome_sequencing_links_mutations_in_parn_and_rtel1_with_familial_pulmonary_fibrosis_and_telomere_shortening.jpg?itok=_B7Pmmmj 640w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_800/public/media/general/2023-05/exome_sequencing_links_mutations_in_parn_and_rtel1_with_familial_pulmonary_fibrosis_and_telomere_shortening.jpg?itok=6C_G5V_H 800w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1040/public/media/general/2023-05/exome_sequencing_links_mutations_in_parn_and_rtel1_with_familial_pulmonary_fibrosis_and_telomere_shortening.jpg?itok=yS31EgV8 1040w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1600/public/media/general/2023-05/exome_sequencing_links_mutations_in_parn_and_rtel1_with_familial_pulmonary_fibrosis_and_telomere_shortening.jpg?itok=Nb4y4W1t 1200w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1280/public/media/general/2023-05/exome_sequencing_links_mutations_in_parn_and_rtel1_with_familial_pulmonary_fibrosis_and_telomere_shortening.jpg?itok=1qm1gUVX 1280w)
Nat. Genet., 2015.
Rare and Common Variants in KIF15 Contribute to Genetic Risk of Idiopathic Pulmonary Fibrosis
![• Rare and Common variants in KIF15 Contribute to Genetic Risk of Idiopathic Pulmonary Fibrosis](https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_200/public/media/general/2023-05/rare_and_common_variants_in_kif15_contribute_to_genetic_risk_of_idiopathic_pulmonary_fibrosis.jpg?itok=0AovXfrF 200w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_260/public/media/general/2023-05/rare_and_common_variants_in_kif15_contribute_to_genetic_risk_of_idiopathic_pulmonary_fibrosis.jpg?itok=--t_2ymk 260w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_320/public/media/general/2023-05/rare_and_common_variants_in_kif15_contribute_to_genetic_risk_of_idiopathic_pulmonary_fibrosis.jpg?itok=4Hzavukx 320w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_400/public/media/general/2023-05/rare_and_common_variants_in_kif15_contribute_to_genetic_risk_of_idiopathic_pulmonary_fibrosis.jpg?itok=nbW2gDS3 400w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_520/public/media/general/2023-05/rare_and_common_variants_in_kif15_contribute_to_genetic_risk_of_idiopathic_pulmonary_fibrosis.jpg?itok=5kuyZQIr 520w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_640/public/media/general/2023-05/rare_and_common_variants_in_kif15_contribute_to_genetic_risk_of_idiopathic_pulmonary_fibrosis.jpg?itok=H9Ir2YFG 640w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_800/public/media/general/2023-05/rare_and_common_variants_in_kif15_contribute_to_genetic_risk_of_idiopathic_pulmonary_fibrosis.jpg?itok=IHfYJPnN 800w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1040/public/media/general/2023-05/rare_and_common_variants_in_kif15_contribute_to_genetic_risk_of_idiopathic_pulmonary_fibrosis.jpg?itok=vQI71waT 1040w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1600/public/media/general/2023-05/rare_and_common_variants_in_kif15_contribute_to_genetic_risk_of_idiopathic_pulmonary_fibrosis.jpg?itok=k02O--65 1200w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1280/public/media/general/2023-05/rare_and_common_variants_in_kif15_contribute_to_genetic_risk_of_idiopathic_pulmonary_fibrosis.jpg?itok=zOSuOZ4b 1280w)
Am. J. Respir. Crit. Care, 2022.
Using Human Kindreds and Cohorts to Translate Genetic Discoveries
We use human kindreds and cohorts to translate genetic discoveries. We have defined the spectrum of pulmonary fibrosis phenotypes associated with rare variants in telomere-related genes (TERT, TERC, PARN, RTEL1). Regardless of diagnosis or gene mutation, patients typically demonstrate clinical progression. Individuals with inherited pathogenic telomere-shortening mutations have an increased frequency of somatic TERT promoter mutations in leukocytes, which lead to increased telomerase activity and a selective advantage for cell growth and replication.
We have shown that leukocyte telomere length is directly associated with transplant-free survival for IPF patients. Telomere length predicts the rate of pulmonary function decline and adverse effects of immunosuppressive medications. We have begun to investigate the clinical utility of measuring telomere length in the ILD clinic to personalize patient care.
We have leveraged the cohort of patients hospitalized at New York Presbyterian Hospital/Columbia University Irving Medical Center at the start of the pandemic to characterize the post-acute sequelae of COVID-19, including pulmonary fibrosis.
Somatic mutations in telomerase promoter counterbalance germline loss-of-function mutations
![Somatic mutations in telomerase promoter counterbalance germline loss-of-function mutations](https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_200/public/media/general/2023-05/somatic_mutations_in_telomerase_promoter_counterbalance_germline_loss-of-function_mutations.jpg?itok=XjNv2-A8 200w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_260/public/media/general/2023-05/somatic_mutations_in_telomerase_promoter_counterbalance_germline_loss-of-function_mutations.jpg?itok=fg0Dlo1- 260w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_320/public/media/general/2023-05/somatic_mutations_in_telomerase_promoter_counterbalance_germline_loss-of-function_mutations.jpg?itok=jQBl_oND 320w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_400/public/media/general/2023-05/somatic_mutations_in_telomerase_promoter_counterbalance_germline_loss-of-function_mutations.jpg?itok=_g-6YDJx 400w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_520/public/media/general/2023-05/somatic_mutations_in_telomerase_promoter_counterbalance_germline_loss-of-function_mutations.jpg?itok=BGG03IIL 520w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_640/public/media/general/2023-05/somatic_mutations_in_telomerase_promoter_counterbalance_germline_loss-of-function_mutations.jpg?itok=YJQbuwua 640w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_800/public/media/general/2023-05/somatic_mutations_in_telomerase_promoter_counterbalance_germline_loss-of-function_mutations.jpg?itok=ei5BrcZ4 800w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1040/public/media/general/2023-05/somatic_mutations_in_telomerase_promoter_counterbalance_germline_loss-of-function_mutations.jpg?itok=8pmMCUmU 1040w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1600/public/media/general/2023-05/somatic_mutations_in_telomerase_promoter_counterbalance_germline_loss-of-function_mutations.jpg?itok=5DAms9CX 1200w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1280/public/media/general/2023-05/somatic_mutations_in_telomerase_promoter_counterbalance_germline_loss-of-function_mutations.jpg?itok=HyuM_wVO 1280w)
J Clin Invest. 2017.
Telomere-Related Lung Fibrosis is Diagnostically Heterogeneous but Uniformly Progressive
![Telomere-Related Lung Fibrosis is Diagnostically Heterogeneous but Uniformly Progressive](https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_200/public/media/general/2023-05/telomere-related_lung_fibrosis_is_diagnostically_heterogeneous_but_uniformly_progressive.jpg?itok=abcp6n0V 200w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_260/public/media/general/2023-05/telomere-related_lung_fibrosis_is_diagnostically_heterogeneous_but_uniformly_progressive.jpg?itok=O6OWmNqi 260w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_320/public/media/general/2023-05/telomere-related_lung_fibrosis_is_diagnostically_heterogeneous_but_uniformly_progressive.jpg?itok=75RkyAZu 320w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_400/public/media/general/2023-05/telomere-related_lung_fibrosis_is_diagnostically_heterogeneous_but_uniformly_progressive.jpg?itok=LUAuVYWb 400w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_520/public/media/general/2023-05/telomere-related_lung_fibrosis_is_diagnostically_heterogeneous_but_uniformly_progressive.jpg?itok=jTloViUG 520w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_640/public/media/general/2023-05/telomere-related_lung_fibrosis_is_diagnostically_heterogeneous_but_uniformly_progressive.jpg?itok=n9rTQziV 640w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_800/public/media/general/2023-05/telomere-related_lung_fibrosis_is_diagnostically_heterogeneous_but_uniformly_progressive.jpg?itok=fIcG1Fql 800w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1040/public/media/general/2023-05/telomere-related_lung_fibrosis_is_diagnostically_heterogeneous_but_uniformly_progressive.jpg?itok=xWVm-8Vm 1040w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1600/public/media/general/2023-05/telomere-related_lung_fibrosis_is_diagnostically_heterogeneous_but_uniformly_progressive.jpg?itok=O_NfA-UL 1200w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1280/public/media/general/2023-05/telomere-related_lung_fibrosis_is_diagnostically_heterogeneous_but_uniformly_progressive.jpg?itok=rvLFkrM0 1280w)
Eur Respir J. 2016.
Effect of Telomere Length on Survival in Idiopathic Pulmonary Fibrosis: an Observational Study With Independent Validation
![Effect of Telomere Length on Survival in Idiopathic Pulmonary Fibrosis](https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_200/public/media/general/2023-05/effect_of_telomere_length_on_survival_in_idiopathic_pulmonary_fibrosis.jpg?itok=vHlzAIOt 200w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_260/public/media/general/2023-05/effect_of_telomere_length_on_survival_in_idiopathic_pulmonary_fibrosis.jpg?itok=gTJseteO 260w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_320/public/media/general/2023-05/effect_of_telomere_length_on_survival_in_idiopathic_pulmonary_fibrosis.jpg?itok=R-o9moJd 320w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_400/public/media/general/2023-05/effect_of_telomere_length_on_survival_in_idiopathic_pulmonary_fibrosis.jpg?itok=hN3-xmV6 400w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_520/public/media/general/2023-05/effect_of_telomere_length_on_survival_in_idiopathic_pulmonary_fibrosis.jpg?itok=dDOO1cJc 520w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_640/public/media/general/2023-05/effect_of_telomere_length_on_survival_in_idiopathic_pulmonary_fibrosis.jpg?itok=dqbQJyab 640w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_800/public/media/general/2023-05/effect_of_telomere_length_on_survival_in_idiopathic_pulmonary_fibrosis.jpg?itok=RSlWYX7g 800w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1040/public/media/general/2023-05/effect_of_telomere_length_on_survival_in_idiopathic_pulmonary_fibrosis.jpg?itok=-jE7PnJB 1040w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1600/public/media/general/2023-05/effect_of_telomere_length_on_survival_in_idiopathic_pulmonary_fibrosis.jpg?itok=Gsn9dS-F 1200w, https://www.vagelos.columbia.edu/sites/default/files/styles/cola_media_1280/public/media/general/2023-05/effect_of_telomere_length_on_survival_in_idiopathic_pulmonary_fibrosis.jpg?itok=12A02hCH 1280w)
Lancet Respir Med. 2014.
Telomere Length and Use of Immunosuppressive Medications in Idiopathic Pulmonary Fibrosis
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