Clinical Focus


  • Critical Care Medicine

Academic Appointments


Professional Education


  • Residency: Boston Medical Center (2017) MA
  • Board Certification: American Board of Internal Medicine, Critical Care Medicine (2020)
  • Fellowship: Stanford University Pulmonary and Critical Care Fellowship (2020) CA
  • Board Certification: American Board of Internal Medicine, Pulmonary Disease (2019)
  • Board Certification: American Board of Internal Medicine, Internal Medicine (2017)

All Publications


  • Novel TRAF2 variant and KDR deletion are implicated in the pathogenesis of pulmonary arterial hypertension Gallego, N., Pienkos, S., Condon, D., Cruz, A., Ochoa, N., Nevado, J., Arias, P., Agarwal, S., Patel, H., Chakraborty, A., Lapunzina, P., Escribano, P., de Jesus, V., Tenorio, J. SPRINGERNATURE. 2022: 197-198
  • "NOVEL MECHANISMS TARGETED BY DRUG TRIALS IN PULMONARY ARTERIAL HYPERTENSION". Chest Condon, D. F., Agarwal, S., Chakraborty, A., Auer, N., Vazquez, R., Patel, H., Zamanian, R. T., de Jesus Perez, V. A., Condon, D. F. 2021

    Abstract

    Pulmonary arterial hypertension (PAH) is a rare disease associated with abnormally elevated pulmonary pressures and right heart failure resulting in high morbidity and mortality. While PAH prognosis has improved with the introduction of pulmonary vasodilators, disease progression remains a major problem. Given that available therapies are inadequate for preventing small vessel loss and obstruction, there is an active interest in identifying drugs capable of targeting angiogenesis and mechanisms involved in regulation of cell growth and fibrosis. Among the mechanisms linked to PAH pathogenesis, recent preclinical studies have identified promising compounds that are currently being tested in clinical trials. These drugs target seven of the major mechanisms associated with PAH pathogenesis: BMP signaling, tyrosine kinase receptors, estrogen metabolism, extracellular matrix, angiogenesis, epigenetics, and serotonin metabolism. In this review, we will discuss the preclinical studies that led to prioritization of these mechanisms and will discuss recently completed and ongoing phase 2/3 trials using novel interventions such as sotatercept, anastrozole, rodatristat ethyl, tyrosine kinase inhibitors, and endothelial progenitor cells among others. We anticipate that the next generation of compounds will build upon the success of the current standard of care and improve clinical outcomes and quality of life of patients afflicted with PAH.

    View details for DOI 10.1016/j.chest.2021.10.010

    View details for PubMedID 34655569

  • Lung Pericytes in Pulmonary Vascular Physiology and Pathophysiology. Comprehensive Physiology Yuan, K., Agarwal, S., Chakraborty, A., Condon, D. F., Patel, H., Zhang, S., Huang, F., Mello, S. A., Kirk, O. I., Vasquez, R., de Jesus Perez, V. A. 2021; 11 (3): 2227-2247

    Abstract

    Pericytes are mesenchymal-derived mural cells localized within the basement membrane of pulmonary and systemic capillaries. Besides structural support, pericytes control vascular tone, produce extracellular matrix components, and cytokines responsible for promoting vascular homeostasis and angiogenesis. However, pericytes can also contribute to vascular pathology through the production of pro-inflammatory and pro-fibrotic cytokines, differentiation into myofibroblast-like cells, destruction of the extracellular matrix, and dissociation from the vessel wall. In the lung, pericytes are responsible for maintaining the integrity of the alveolar-capillary membrane and coordinating vascular repair in response to injury. Loss of pericyte communication with alveolar capillaries and a switch to a pro-inflammatory/pro-fibrotic phenotype are common features of lung disorders associated with vascular remodeling, inflammation, and fibrosis. In this article, we will address how to differentiate pericytes from other cells, discuss the molecular mechanisms that regulate the interactions of pericytes and endothelial cells in the pulmonary circulation, and the experimental tools currently used to study pericyte biology both in vivo and in vitro. We will also discuss evidence that links pericytes to the pathogenesis of clinically relevant lung disorders such as pulmonary hypertension, idiopathic lung fibrosis, sepsis, and SARS-COVID. Future studies dissecting the complex interactions of pericytes with other pulmonary cell populations will likely reveal critical insights into the origin of pulmonary diseases and offer opportunities to develop novel therapeutics to treat patients afflicted with these devastating disorders. © 2021 American Physiological Society. Compr Physiol 11:2227-2247, 2021.

    View details for DOI 10.1002/cphy.c200027

    View details for PubMedID 34190345

  • Novel TNIP2 and TRAF2 Variants Are Implicated in the Pathogenesis of Pulmonary Arterial Hypertension FRONTIERS IN MEDICINE Pienkos, S., Gallego, N., Condon, D. F., Cruz-Utrilla, A., Ochoa, N., Nevado, J., Arias, P., Agarwal, S., Patel, H., Chakraborty, A., Lapunzina, P., Escribano, P., Tenorio-Castano, J., de Jesus Perez, V. A., Spanish PAH Consortium 2021; 8: 625763

    Abstract

    Background: Pulmonary arterial hypertension (PAH) is a rare disease characterized by pulmonary vascular remodeling and right heart failure. Specific genetic variants increase the incidence of PAH in carriers with a family history of PAH, those who suffer from certain medical conditions, and even those with no apparent risk factors. Inflammation and immune dysregulation are related to vascular remodeling in PAH, but whether genetic susceptibility modifies the PAH immune response is unclear. TNIP2 and TRAF2 encode for immunomodulatory proteins that regulate NF-κB activation, a transcription factor complex associated with inflammation and vascular remodeling in PAH. Methods: Two unrelated families with PAH cases underwent whole-exome sequencing (WES). A custom pipeline for variant prioritization was carried out to obtain candidate variants. To determine the impact of TNIP2 and TRAF2 in cell proliferation, we performed an MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay on healthy lung pericytes transfected with siRNA specific for each gene. To measure the effect of loss of TNIP2 and TRAF2 on NF-kappa-beta (NF-κB) activity, we measured levels of Phospho-p65-NF-κB in siRNA-transfected pericytes using western immunoblotting. Results: We discovered a novel missense variant in the TNIP2 gene in two affected individuals from the same family. The two patients had a complex form of PAH with interatrial communication and scleroderma. In the second family, WES of the proband with PAH and primary biliary cirrhosis revealed a de novo protein-truncating variant in the TRAF2. The knockdown of TNIP2 and TRAF2 increased NF-κB activity in healthy lung pericytes, which correlated with a significant increase in proliferation over 24 h. Conclusions: We have identified two rare novel variants in TNIP2 and TRAF2 using WES. We speculate that loss of function in these genes promotes pulmonary vascular remodeling by allowing overactivation of the NF-κB signaling activity. Our findings support a role for WES in helping identify novel genetic variants associated with dysfunctional immune response in PAH.

    View details for DOI 10.3389/fmed.2021.625763

    View details for Web of Science ID 000649921700001

    View details for PubMedID 33996849

    View details for PubMedCentralID PMC8119639

  • THE CANCER HYPOTHESIS OF PULMONARY ARTERIAL HYPERTENSION: THE NEXT TEN YEARS. American journal of physiology. Lung cellular and molecular physiology Condon, D., Agarwal, S., Chakraborty, A., de Jesus Perez, V. A. 2020

    View details for DOI 10.1152/ajplung.00057.2020

    View details for PubMedID 32186209

  • Mural Cell SDF1 Signaling is Associated with the Pathogenesis of Pulmonary Arterial Hypertension. American journal of respiratory cell and molecular biology Yuan, K. n., Liu, Y. n., Zhang, Y. n., Nathan, A. n., Tian, W. n., Yu, J. n., Sweatt, A. J., Condon, D. n., Chakraborty, A. n., Agarwal, S. n., Auer, N. n., Zhang, S. n., Wu, J. C., Zamanian, R. T., Nicolls, M. R., de Jesus Perez, V. A. 2020

    Abstract

    Pulmonary artery smooth muscle cells (PASMCs) and pericytes are NG2+ mural cells that provide structural support to pulmonary arteries and capillaries. In pulmonary arterial hypertension (PAH), both mural cell types contribute to PA muscularization but whether similar mechanisms are responsible for their behavior is unknown.RNA-Seq was used to compare the gene profile of pericytes and PASMCs from PAH and healthy lungs. NG2-Cre-ER mice were used to generate NG2-selective reporter mice (NG2tdT) for cell lineage identification and tamoxifen-inducible mice for NG2-selective SDF1 knockout (SDF1NG2-KO).Hierarchical clustering of RNA-seq data demonstrated that the genetic profile of PAH pericytes and PASMCs is highly similar. Cellular lineage staining studies on NG2tdT mice in chronic hypoxia showed that similar to PAH, tdT+ cells accumulate in muscularized microvessels and demonstrate significant upregulation of SDF1, a chemokine involved in chemotaxis and angiogenesis. Compared to controls, SDF1NG2-KO mice in chronic hypoxia had reduced muscularization and lower abundance of NG2+ cells around microvessels. SDF1 stimulation in healthy pericytes induced greater contractility and impaired their capacity to establish endothelial-pericyte communications. In contrast, SDF1 knockdown reduced PAH pericyte contractility and improved their capacity to associate with vascular tubes in co-culture.SDF1 is upregulated in NG2+ mural cells and is associated with PA muscularization. Targeting SDF1 could help prevent and/or reverse muscularization in PAH.

    View details for DOI 10.1165/rcmb.2019-0401OC

    View details for PubMedID 32084325

  • ANATOMIC, GENETIC AND FUNCTIONAL PROPERTIES OF THE RETINAL CIRCULATION IN PULMONARY HYPERTENSION Pulmonary Circulation Nickel, N. P., Shamskhou, E. A., Razeen, M., Condon, D., Messentier, L., Dubra, A., Liao, Y., Zamanian, R. T., Yuan, K., de Jesus Perez, V. A. 2020

    View details for DOI 10.1177/2045894020905508

  • From 2D to 3D: Promising Advances in Imaging Lung Structure. Frontiers in medicine Klouda, T. n., Condon, D. n., Hao, Y. n., Tian, W. n., Lvova, M. n., Chakraborty, A. n., Nicolls, M. R., Zhou, X. n., Raby, B. A., Yuan, K. n. 2020; 7: 343

    Abstract

    The delicate structure of murine lungs poses many challenges for acquiring high-quality images that truly represent the living lung. Here, we describe several optimized procedures for obtaining and imaging murine lung tissue. Compared to traditional paraffin cross-section and optimal cutting temperature (OCT), agarose-inflated vibratome sections (aka precision-cut lung slices), combines comparable structural preservation with experimental flexibility. In particular, we discuss an optimized procedure to precision-cut lung slices that can be used to visualize three-dimensional cell-cell interactions beyond the limitations of two-dimensional imaging. Super-resolution microscopy can then be used to reveal the fine structure of lung tissue's cellular bodies and processes that regular confocal cannot. Lastly, we evaluate the entire lung vasculature with clearing technology that allows imaging of the entire volume of the lung without sectioning. In this manuscript, we combine the above procedures to create a novel and evolutionary method to study cell behavior ex vivo, trace and reconstruct pulmonary vasculature, address fundamental questions relevant to a wide variety of vascular disorders, and perceive implications to better imaging clinical tissue.

    View details for DOI 10.3389/fmed.2020.00343

    View details for PubMedID 32766264

    View details for PubMedCentralID PMC7381109

  • The 6th World Symposium on Pulmonary Hypertension: what's old is new. F1000Research Condon, D. F., Nickel, N. P., Anderson, R. n., Mirza, S. n., de Jesus Perez, V. A. 2019; 8

    Abstract

    In February 2018, the 6th World Symposium on Pulmonary Hypertension (WSPH) brought together experts from various disciplines to review the most relevant clinical and scientific advances in the field of PH over the last 5 years. Based on careful review and discussions by members of the different task forces, major revisions were made on the hemodynamic definition for various forms of PH and new genes were added to the list of genetic markers associated with pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease. In addition, the use of risk stratification tools was encouraged as a strategy to reduce one-year mortality risk in PAH patients through early implementation of PAH therapies. While members of the medical community are still debating some of the proposed changes, the new WSPH guidelines advocate early diagnosis and initiation of combination therapy to reduce mortality and improve quality of life in patients with PH.

    View details for DOI 10.12688/f1000research.18811.1

    View details for PubMedID 31249672

    View details for PubMedCentralID PMC6584967

  • Diagnosis and Management of Pulmonary Hypertension in the Modern Era: Insights from the 6th World Symposium. Pulmonary therapy Thomas, C. A., Anderson, R. J., Condon, D. F., de Jesus Perez, V. A. 2019

    Abstract

    The past 20 years have seen major advances in the diagnosis and management of pulmonary hypertension, a disease associated with significant morbidity and mortality. The 6th World Symposium in Pulmonary Hypertension (WSPH) took place in February 2018 and attempted to consolidate the current knowledge in the field into practical recommendations to help prioritize an action plan to improve patient outcomes and identify future research directions. In this review, we will summarize the highlights of the 6th WSPH proceedings, including revisions to the hemodynamic definitions and classification of the various types of pulmonary hypertension, genetic advances, approaches to risk stratification, and updated treatment algorithms.

    View details for DOI 10.1007/s41030-019-00105-5

    View details for PubMedID 32048239

  • Human dendritic cells exhibit a pronounced type I IFN signature following Leishmania major infection that is required for IL-12 induction. Journal of immunology (Baltimore, Md. : 1950) Favila, M. A., Geraci, N. S., Zeng, E., Harker, B., Condon, D., Cotton, R. N., Jayakumar, A., Tripathi, V., McDowell, M. A. 2014; 192 (12): 5863-72

    Abstract

    Leishmania major-infected human dendritic cells (DCs) exhibit a marked induction of IL-12, ultimately promoting a robust Th1-mediated response associated with parasite killing and protective immunity. The host cell transcription machinery associated with the specific IL-12 induction observed during L. major infection remains to be thoroughly elucidated. In this study, we used Affymetrix GeneChip (Affymetrix) to globally assess the host cell genes and pathways associated with early L. major infection in human myeloid-derived DCs. Our data revealed 728 genes were significantly differentially expressed and molecular signaling pathway revealed that the type I IFN pathway was significantly enriched. Addition of a neutralizing type I IFN decoy receptor blocked the expression of IRF7 and IL-12p40 during DC infection, indicating the L. major-induced expression of IL-12p40 is dependent upon the type I IFN signaling pathway. In stark contrast, IL-12p40 expression is not elicited by L. donovani, the etiological agent of deadly visceral leishmaniasis. Therefore, we examined the gene expression profile for several IFN response genes in L. major versus L. donovani DC infections. Our data revealed that L. major, but not L. donovani, induces expression of IRF2, IRF7, and IFIT5, implicating the regulation of type I IFN-associated signaling pathways as mediating factors toward the production of IL-12.

    View details for DOI 10.4049/jimmunol.1203230

    View details for PubMedID 24808365

    View details for PubMedCentralID PMC4052223

  • Phenyl-alpha-tert-butyl-nitrone and benzonidazole treatment controlled the mitochondrial oxidative stress and evolution of cardiomyopathy in chronic chagasic Rats. Journal of the American College of Cardiology Wen, J. J., Gupta, S., Guan, Z., Dhiman, M., Condon, D., Lui, C., Garg, N. J. 2010; 55 (22): 2499-508

    Abstract

    The purpose of this study was to determine the pathological importance of oxidative stress-induced injurious processes in chagasic heart dysfunction.Trypanosoma cruzi-induced inflammatory pathology and a feedback cycle of mitochondrial dysfunction and oxidative stress may contribute to Chagas disease.Sprague-Dawley rats were infected with T. cruzi and treated with phenyl-alpha-tert-butylnitrone (PBN), an antioxidant, and/or benzonidazole (BZ), an antiparasitic agent. We monitored myocardial parasite burden, oxidative adducts, mitochondrial complex activities, respiration, and adenosine triphosphate synthesis rates, and inflammatory and cardiac remodeling responses during disease development. The cardiac hemodynamics was determined for all rats.Benzonidazole (not PBN) decreased the parasite persistence and immune adverse events (proinflammatory cytokine expression, beta-nicotinamide adenine dinucleotide phosphate oxidase and myeloperoxidase activities, and inflammatory infiltrate) in chronically infected hearts. PBN +/- BZ (not BZ alone) decreased the mitochondrial reactive oxygen species level, oxidative adducts (malonyldialdehyde, 4-hydroxynonenal, carbonyls), hypertrophic gene expression (atrial natriuretic peptide, B-type natriuretic peptide, alpha-skeletal actin), and collagen deposition and preserved the respiratory chain efficiency and energy status in chronically infected hearts. Subsequently, LV dysfunction was prevented in PBN +/- BZ-treated chagasic rats.BZ treatment after the acute stage decreased the parasite persistence and inflammatory pathology. Yet, oxidative adducts, mitochondrial dysfunction, and remodeling responses persisted and contributed to declining cardiac function in chagasic rats. Combination treatment (PBN + BZ) was beneficial in arresting the T. cruzi-induced inflammatory and oxidative pathology and chronic heart failure in chagasic rats.

    View details for DOI 10.1016/j.jacc.2010.02.030

    View details for PubMedID 20510218

    View details for PubMedCentralID PMC2887697