Pulmonary Biology
Kalinichenko Lab

Kalinichenko Research Lab

The lab is investigating novel transcriptional mechanisms critical for embryonic lung development, lung injury/ repair and lung carcinogenesis. The focus is on winged helix/forkhead box (FOX) proteins and their role in regulating cell signaling pathways required for cellular proliferation, differentiation, motility and survival, to ultimately identify novel molecular mechanisms that cause human lung malformations, promote chronic respiratory diseases or contribute to lung cancer.

Our current projects use mouse models with loss-of-function and gain-of function for various FOX genes and novel pharmacological modulators of FOX proteins to identify transcriptional mechanisms impaired in pediatric and adult pulmonary diseases. These diseases include alveolar capillary dysplasia (ACD), bronchopulmonary dysplasia (BPD), acute lung injury (ALI), asthma and non-small cell lung cancer (NSCLC). Our long-term goal is to discover novel therapeutic approaches and generate novel FDA-approved drugs for treatment of these severe respiratory disorders.

Publications

Ren, X; Ustiyan, V; Guo, M; Wang, G; Bolte, C; Zhang, Y; Xu, Y; Whitsett, JA; Kalin, TV; Kalinichenko, VV. Postnatal Alveologenesis Depends on FOXF1 Signaling in c-KIT+ Endothelial Progenitor Cells. American Journal of Respiratory and Critical Care Medicine. 2019; 200:1164-1176.

Pradhan, A; Dunn, A; Ustiyan, V; Bolte, C; Wang, G; Whitsett, JA; Zhang, Y; Porollo, A; Hu, Y; Xiao, R; et al. The S52F FOXF1 Mutation Inhibits STAT3 Signaling and Causes Alveolar Capillary Dysplasia. American Journal of Respiratory and Critical Care Medicine. 2019; 200:1045-1056.

Sun, L; Ren, X; Wang, I; Pradhan, A; Zhang, Y; Flood, HM; Han, B; Whitsett, JA; Kalin, TV; Kalinichenko, VV. The FOXM1 inhibitor RCM-1 suppresses goblet cell metaplasia and prevents IL-13 and STAT6 signaling in allergen-exposed mice. Science Signaling. 2017; 10:eaai8583.

Cai, Y; Bolte, C; Le, T; Goda, C; Xu, Y; Kalin, TV; Kalinichenko, VV. FOXF1 maintains endothelial barrier function and prevents edema after lung injury. Science Signaling. 2016; 9:ra40.

Ren, X; Ustiyan, V; Pradhan, A; Cai, Y; Havrilak, JA; Bolte, CS; Shannon, JM; Kalin, TV; Kalinichenko, VV. FOXF1 transcription factor is required for formation of embryonic vasculature by regulating VEGF signaling in endothelial cells. Circulation Research. 2014; 115:709-720.

Ren, X; Shah, TA; Ustiyan, V; Zhang, Y; Shinn, J; Chen, G; Whitsett, JA; Kalin, TV; Kalinichenko, VV. FOXM1 promotes allergen-induced goblet cell metaplasia and pulmonary inflammation. Molecular and Cellular Biology. 2013; 33:371-386.

Wang, I; Snyder, J; Zhang, Y; Lander, J; Nakafuku, Y; Lin, J; Chen, G; Kalin, TV; Whitsett, JA; Kalinichenko, VV. Foxm1 mediates cross talk between Kras/mitogen-activated protein kinase and canonical Wnt pathways during development of respiratory epithelium. Molecular and Cellular Biology. 2012; 32:3838-3850.

Kalin, TV; Wang, I; Meliton, L; Zhang, Y; Wert, SE; Ren, X; Snyder, J; Bell, SM; Jr, GL; Whitsett, JA; et al. Forkhead Box m1 transcription factor is required for perinatal lung function. Proceedings of the National Academy of Sciences of USA. 2008; 105:19330-19335.

Malin, D; Kim, I; Boetticher, E; Kalin, TV; Ramakrishna, S; Meliton, L; Ustiyan, V; Zhu, X; Kalinichenko, VV. Forkhead box F1 is essential for migration of mesenchymal cells and directly induces integrin-beta3 expression. Molecular and Cellular Biology. 2007; 27:2486-2498.

Damianos, A; Kalinichenko, VV. Hedgehog and Platelet-derived Growth Factor Collaborate to Guide Fibroblasts during Alveolarization. American Journal of Respiratory Cell and Molecular Biology. 2023; 68:472-474.

Pradhan, A; Che, L; Ustiyan, V; Reza, AA; Pek, NM; Zhang, Y; Alber, AB; Kalin, TR; Wambach, JA; Gu, M; et al. Novel FOXF1-Stabilizing Compound TanFe Stimulates Lung Angiogenesis in Alveolar Capillary Dysplasia. American Journal of Respiratory and Critical Care Medicine. 2023; 207:1042-1054.

Reza, AA; Kohram, F; Reza, HA; Kalin, TR; Kannan, PS; Zacharias, WJ; Kalinichenko, VV. FOXF1 Regulates Alveolar Epithelial Morphogenesis through Transcriptional Activation of Mesenchymal WNT5A. American Journal of Respiratory Cell and Molecular Biology. 2023; 68:430-443.

Donovan, J; Deng, Z; Bian, F; Shukla, S; Gomez-Arroyo, J; Shi, D; Kalinichenko, VV; Kalin, TV. Improving anti-tumor efficacy of low-dose Vincristine in rhabdomyosarcoma via the combination therapy with FOXM1 inhibitor RCM1. Frontiers in Oncology. 2023; 13:1112859.

Wang, G; Wen, B; Deng, Z; Zhang, Y; Kolesnichenko, OA; Ustiyan, V; Pradhan, A; Kalin, TV; Kalinichenko, VV. Endothelial progenitor cells stimulate neonatal lung angiogenesis through FOXF1-mediated activation of BMP9/ACVRL1 signaling. Nature Communications. 2022; 13:2080.

Wen, B; Wang, G; Li, E; Kolesnichenko, OA; Tu, Z; Divanovic, S; Kalin, TV; Kalinichenko, VV. In vivo generation of bone marrow from embryonic stem cells in interspecies chimeras. eLife. 2022; 11:e74018.

Ribeiro, R; Macedo, JC; Costa, M; Ustiyan, V; Shindyapina, AV; Tyshkovskiy, A; Gomes, RN; Castro, JP; Kalin, TV; Vasques-Nóvoa, F; et al. In vivo cyclic induction of the FOXM1 transcription factor delays natural and progeroid aging phenotypes and extends healthspan. 2022; 2:397-411.

Toth, A; Steinmeyer, S; Kannan, P; Gray, J; Jackson, CM; Mukherjee, S; Demmert, M; Sheak, JR; Benson, D; Kitzmiller, J; et al. Inflammatory blockade prevents injury to the developing pulmonary gas exchange surface in preterm primates. Science Translational Medicine. 2022; 14:eabl8574.

Damianos, A; Xu, K; Kalin, GT; Kalinichenko, VV. Placental tissue stem cells and their role in neonatal diseases. Seminars in Fetal and Neonatal Medicine. 2022; 27:101322.

Sun, X; Perl, AK; Li, R; Bell, SM; Sajti, E; Kalinichenko, VV; Kalin, TV; Misra, RS; Deshmukh, H; Clair, G; et al. A census of the lung: CellCards from LungMAP. Developmental Cell. 2022; 57:112-145.e2.

Kalinichenko, VV; Bolte, CS; Kalin, TV. Transcription Factors: Forkhead Box (FOX) ☆. Encyclopedia of Respiratory Medicine. : Elsevier; Elsevier; 2022.

Kolesnichenko, OA; Whitsett, JA; Kalin, TV; Kalinichenko, VV. Therapeutic Potential of Endothelial Progenitor Cells in Pulmonary Diseases. American Journal of Respiratory Cell and Molecular Biology. 2021; 65:473-488.

Deng, Z; Lin, J; Bud’ko, SL; Webster, B; Kalin, TV; Kalinichenko, VV; Shi, D. Dual Targeting with Cell Surface Electrical Charge and Folic Acid via Superparamagnetic Fe3O4@Cu2-xS for Photothermal Cancer Cell Killing. Cancers. 2021; 13:5275.

Sun, F; Wang, G; Pradhan, A; Xu, K; Gomez-Arroyo, J; Zhang, Y; Kalin, GT; Deng, Z; Vagnozzi, RJ; He, H; et al. Nanoparticle Delivery of STAT3 Alleviates Pulmonary Hypertension in a Mouse Model of Alveolar Capillary Dysplasia. Circulation. 2021; 144:539-555.

Wang, G; Wen, B; Ren, X; Li, E; Zhang, Y; Guo, M; Xu, Y; Whitsett, JA; Kalin, TV; Kalinichenko, VV. Generation of Pulmonary Endothelial Progenitor Cells for Cell-based Therapy Using Interspecies Mouse-Rat Chimeras. American Journal of Respiratory and Critical Care Medicine. 2021; 204:326-338.

Li, E; Ustiyan, V; Wen, B; Kalin, GT; Whitsett, JA; Kalin, TV; Kalinichenko, VV. Blastocyst complementation reveals that NKX2-1 establishes the proximal-peripheral boundary of the airway epithelium. Developmental Dynamics. 2021; 250:1001-1020.

Milewski, D; Shukla, S; Gryder, BE; Pradhan, A; Donovan, J; Sudha, P; Vallabh, S; Pyros, A; Xu, Y; Barski, A; et al. FOXF1 is required for the oncogenic properties of PAX3-FOXO1 in rhabdomyosarcoma. Oncogene: Including Oncogene Reviews. 2021; 40:2182-2199.

Deng, Z; Kalin, GT; Shi, D; Kalinichenko, VV. Nanoparticle Delivery Systems with Cell-Specific Targeting for Pulmonary Diseases. American Journal of Respiratory Cell and Molecular Biology. 2021; 64:292-307.

Wen, B; Li, E; Ustiyan, V; Wang, G; Guo, M; Na, CL; Kalin, GT; Galvan, V; Xu, Y; Weaver, TE; et al. In Vivo Generation of Lung and Thyroid Tissues from Embryonic Stem Cells Using Blastocyst Complementation. American Journal of Respiratory and Critical Care Medicine. 2021; 203:471-483.

Nasr, T; Holderbaum, AM; Chaturvedi, P; Agarwal, K; Kinney, JL; Daniels, K; Trisno, SL; Ustiyan, V; Shannon, JM; Wells, JM; et al. Disruption of a hedgehog-foxf1-rspo2 signaling axis leads to tracheomalacia and a loss of sox9+ tracheal chondrocytes. DMM Disease Models and Mechanisms. 2021; 14:dmm046573.

Cappelletti, M; Doll, JR; Stankiewicz, TE; Lawson, MJ; Sauer, V; Wen, B; Kalinichenko, VV; Sun, X; Tilburgs, T; Divanovic, S. Maternal regulation of inflammatory cues is required for induction of preterm birth. JCI insight. 2020; 5:e138812.

Pradhan, A; Kalin, TV; Kalinichenko, VV. Genome Editing for Rare Diseases. Current stem cell reports. 2020; 6:41-51.

Bolte, C; Ustiyan, V; Ren, X; Dunn, AW; Pradhan, A; Wang, G; Kolesnichenko, OA; Deng, Z; Zhang, Y; Shi, D; et al. Nanoparticle Delivery of Proangiogenic Transcription Factors into the Neonatal Circulation Inhibits Alveolar Simplification Caused by Hyperoxia. American Journal of Respiratory and Critical Care Medicine. 2020; 202:100-111.

Black, M; Arumugam, P; Shukla, S; Pradhan, A; Ustiyan, V; Milewski, D; Kalinichenko, VV; Kalin, TV. FOXM1 nuclear transcription factor translocates into mitochondria and inhibits oxidative phosphorylation. Editor, Fox T. Molecular Biology of the Cell. 2020; 31:1411-1424.

Goda, C; Balli, D; Black, M; Milewski, D; Le, T; Ustiyan, V; Ren, X; Kalinichenko, VV; Kalin, TV. Loss of FOXM1 in macrophages promotes pulmonary fibrosis by activating p38 MAPK signaling pathway. Editor, Barsh GS. PLoS Genetics. 2020; 16:e1008692.

Bolte, C; Kalin, TV; Kalinichenko, VV. Molecular, cellular, and bioengineering approaches to stimulate lung regeneration after injury. Seminars in Cell and Developmental Biology. 2020; 100:101-108.

Whitsett, JA; Zacharias, W; Swarr, D; Kalinichenko, VV. Chapter 67 Cell- and tissue-based therapies for lung disease. Principles of Tissue Engineering. : Elsevier; Elsevier; 2020.

Kurahashi, T; Yoshida, Y; Ogura, S; Egawa, M; Furuta, K; Hikita, H; Kodama, T; Sakamori, R; Kiso, S; Kamada, Y; et al. Forkhead Box M1 Transcription Factor Drives Liver Inflammation Linking to Hepatocarcinogenesis in Mice. CMGH Cellular and Molecular Gastroenterology and Hepatology. 2020; 9:425-446.

Hasegawa, T; Kikuta, J; Sudo, T; Matsuura, Y; Matsui, T; Simmons, S; Ebina, K; Hirao, M; Okuzaki, D; Yoshida, Y; et al. Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1. Nature Immunology. 2019; 20:1631-1643.

Ren, X; Ustiyan, V; Guo, M; Wang, G; Bolte, C; Zhang, Y; Xu, Y; Whitsett, JA; Kalin, TV; Kalinichenko, VV. Postnatal Alveologenesis Depends on FOXF1 Signaling in c-KIT+ Endothelial Progenitor Cells. American Journal of Respiratory and Critical Care Medicine. 2019; 200:1164-1176.

Pradhan, A; Dunn, A; Ustiyan, V; Bolte, C; Wang, G; Whitsett, JA; Zhang, Y; Porollo, A; Hu, Y; Xiao, R; et al. The S52F FOXF1 Mutation Inhibits STAT3 Signaling and Causes Alveolar Capillary Dysplasia. American Journal of Respiratory and Critical Care Medicine. 2019; 200:1045-1056.

Shukla, S; Milewski, D; Pradhan, A; Rama, N; Rice, K; Le, T; Flick, MJ; Vaz, S; Zhao, X; Setchell, KD; et al. The FOXM1 Inhibitor RCM-1 Decreases Carcinogenesis and Nuclear β-Catenin. Molecular Cancer Therapeutics. 2019; 18:1217-1229.

Flood, HM; Bolte, C; Dasgupta, N; Sharma, A; Zhang, Y; Gandhi, CR; Kalin, TV; Kalinichenko, VV. The Forkhead box F1 transcription factor inhibits collagen deposition and accumulation of myofibroblasts during liver fibrosis. Biology Open. 2019; 8:bio039800.

Whitsett, JA; Kalin, TV; Xu, Y; Kalinichenko, VV. Building and Regenerating the Lung Cell by Cell. Physiological Reviews. 2019; 99:513-554.