7203 Marsico Hall
Specialty Areas (clinical or research areas of expertise): Critical Care Medicine, Acute Respiratory Distress Syndrome, and Pulmonary Medicine
Chronology: BS, Summa Cum Laude: Texas A&M University, 1999; MD/PhD, University of Texas Southwestern Medical School, 2007; Resident: Johns Hopkins Hospital, 2007-2010; Pulmonary and Critical Care Fellow, Johns Hopkins Hospital, 2010-2014; Clinical Instructor, University of North Carolina, 2014-2017; Assistant Professor, Tenure Track, 2017-present
Description of research and/or clinical interests:
Our research interests are in how the lung resolves injury and undergoes repair after damage. Acute events such as pneumonia, inhalational injury, trauma or sepsis often damage the lung, which consequently can impede its primary function, gas exchange. The clinical syndrome these events can lead to is termed Acute Respiratory Distress Syndrome (ARDS). ARDS is a common pulmonary disease often seen and treated in intensive care units. Despite decades of research into the pathogenesis underlying the development of ARDS, mortality remains high. Our laboratory has built upon exciting observations by our group and others on the importance of how the lung repairs after injury. One type of white blood cell, the Foxp3+ regulatory T cell (Treg), appears important in the resolution of ARDS in both experimental models of lung injury and importantly Treg are present in patients with ARDS. Tregs contribute to the recovery from experimental acute lung injury (ALI) through modulating immune responses and enhancing alveolar epithelial proliferation and tissue repair.
The laboratory’s current funding (K08HL129075, R03HL145255 and The Acute Lung Injury Research Fund from the Hettinger Foundation) explores lymphocyte and epithelium interactions during resolution of experimental lung injury along with expanding our findings to human data and samples obtained from patients with ARDS. These studies provide a broader understanding of Treg-specific contributions towards the reparative process in the resolution of lung injury. Our work may potentially uncover new targets to help accelerate recovery and improve the quality of repaired lung tissue for patients with lung diseases.
Major areas of interests include:
- Studies investigating the mechanisms of Foxp3+regulatory T cells (Tregs) in promoting resolution of lung injury
- Lymphocyte interactions with the distal lung epithelium
- Clinical and translational studies of Acute Respiratory Distress Syndrome (ARDS)
Identifying and elucidating mechanisms of lung resolution will allow for the potential development of therapeutic approaches to minimize collateral tissue damage without adversely altering the beneficial response to injury.
Laboratory Website: https://www.med.unc.edu/medicine/mocklab/
Acute Respiratory Distress Syndrome. University of North Carolina Department of Medicine Chairman’s Corner. April 6, 2016; J. Mock and R. Falk
Care of ARDS
Selected Bibliography (reverse chronological order):
Norton DL, Ceppe A, Tune MK, McCravy M, Devlin T, Drummond MB, Carson SS, Vincent BG, Hagan RS, Dang H, Doerschuk CM, Mock JR. “Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome.” J Transl Med 18, 427 (2020). PMID: 33176790
Hedrick TL, Murray BP, Hagan RS, Mock JR. “COVID-19: Clean up on IL-6.” Am J Respir Cell Mol Biol. 2020 Oct;63(4):541-543. PMID: 32750259
Mock JR, Dial CF, Tune MK, Gilmore RC, O’Neal WK, Hong D, Doerschuk CM. “The impact of Tregs on the AT2 cell transcriptome during the resolution of acute lung injury and the contributions of IFN-γ.” Am J Respir Cell Mol Biol. 2020 Oct;63(4):464-477. PMID: 32543909
Mock JR, Tune MK, Dial CF, Torres-Castillo J, Hagan RS, Doerschuk CM. “Effects of IFN-γ on immune cell kinetics during the resolution of acute lung injury.” Physiol Rep. 2020 Feb; 8 (3) e14368. PMID: 32061190
Mock JR, Dial CF, Tune MK, Norton DL, Martin JR, Gomez JC, Hagan RS, Hong D, Doerschuk CM. “Transcriptional Analysis of Foxp3+ Regulatory T Cells and Functions of Two Identified Molecules during Resolution of ALI” JCI Insight. 2019 March 21; 4(6). PMID: 30753170
Gomez JC, Dang H, Kanke M, Hagan RS, Mock JR, Kelada SNP, Sethupathy P, Doerschuk CM. “Predicted effects of observed changes in the mRNA and microRNA transcriptome of lung neutrophils during S. pneumoniae pneumonia in mice.” Sci Rep. 2017 Sep 12;7(1). PMID: 28900269
Dial DF, Tune MK, Doerschuk CM, and Mock JR. “Foxp3+ Regulatory T Cell Expression of Keratinocyte Growth Factor Enhances Lung Epithelial Proliferation.” 2017 Aug 1; 57(2) Am. J. Respir. Cell Mol. Biol. PMID: 28296468
Mock JR, Singer BD, and D’Alessio FR. “Flow Cytometric Evaluation of Acute Lung Injury and Repair.” Acute Lung Injury and Repair: Scientific Fundamentals and Methods. Editors: Schnapp LM and Feghali-Bostwick C Springer 2017. pages 85-106.
Mock JR, Kolb TK, Illei PB, Yang SC, Lederman HM, and Merlo CA. “Bronchus Associated Lymphoid Tissue in Kabuki Syndrome with Associated Hyper-IgM Syndrome/Common Variable Immunodeficiency” Am J Respir Crit Care Med. 2016 Aug 15; 194(4):514-515. PMID: 27275756
Singer BD, Mock JR, D’Alessio FR, Aggarwal NR. Mandke P, Johnston L, Damarla M. “Flow-cytometric method for simultaneous analysis of mouse lung epithelial, endothelial, and hematopoietic lineage cells” Am J Physiol Lung Cell Mol Physiol. 2016 May 1;310(9) PMID: 26944088
Kolb TM, Peabody J, Baddoura P, Fallica J, Mock JR, Singer BD, D’Alessio FR, Damarla M, Damico R. “Right ventricular angiogenesis is an early adaptive response to chronic hypoxia-induced pulmonary hypertension” Microcirulation 2015 Sep 9 PMID: 26352923
Limjunyawong N, Mock JR, and Mitzner W. “Instillation and Fixation Methods Useful in Mouse Lung Cancer Research” J. Vis. Exp. (102), e52964, doi:10.3791/52964 (2015).
Singer BD, Mock JR, Garibaldi BT, Aggarwal NR, Sidhaye VK, Florez MA, Chau E, Gibbs KW, Mandke P, Tripathi A, Yegnasubramanian S, King LS, D’Alessio FR. “Regulatory T cell DNA methyltransferase inhibition accelerates resolution of lung inflammation.” Am J Respir Cell Mol Biol. 2015: May; 52(5):641-52 PMID: 25295995
Files DC, Liu C, Pereyra A, Wang Z, Aggarwal NR, D’Alessio FR, Garibaldi BT, Mock JR, Singer BD, Feng X, Lee AL, Philpott S, Lussier S, Purcell L, Chou J, Seeds M, King LS, Morris PE, Delbono O. “Therapeutic Exercise Attenuates Neutrophilic Lung Injury and Skeletal Muscle Wasting.” Sci Transl Med. 2015 Mar 11;7(278):278-32 PMID: 25761888
Mock JR, Garibaldi BT, Aggarwal NR, Singer BD, Chau E, Rabold R, Files DC, Jenkins J, Sidhaye V, Wagner E, D’Alessio FR, and King LS. “CD4+ Foxp3+ Regulatory T Cells Promote Epithelial Proliferation.” Mucosal Immunol. 2014 Nov;7(6):1440-51 PMID: 24850425
Garibalid BT, D’Alessio FR, Mock JR, Files DC, Chau E, Yoshiki E, Drummon MB, Aggarwal NR, Sidhaye V, King LS. Regulatory T cells Reduce Acute Lung Injury Fibroproliferation By Decreasing Fibrocyte Recruitment. Am. J. Respir. Cell Mol. Biol. 2013 Jan;48(1):35-43. PMID: 23002097
D’Alessio FR, Tsushima K, Aggarwal NR, Mock JR, Eto Y, Garibaldi BT, Files DC, Avalos CR, Rodriguez JV, Waickman AT, Reddy SR, Pearse, DB, Sidhaye, VK, Hassoun PM, Crow MT, King LS. Resolution of Experimental Lung Injury by Monocyte-Derived Inducible Nitric Oxide Synthase (iNOS). J Immunol. 2012 Sept 1; 189(5):2234-45 PMID: 22844117
Files DC, D’Alessio FR, Johnston L, Kesari P, Aggarwal NR, Garibaldi BT, Mock JR, Simmers J, DeGorordo A, Murdoch J, Willis MS, Patterson C, Tanskersley CG, Cohn RD, King LS, Crow MT. A Critical Role for Muscle Ring Finger-1 in Acute Lung Injury-associated Skeletal Muscle Wasting. Am. J. Respir. Crit. Care Med. 2012; 185; 825-834. PMID: 22312013