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Luis A Ortiz, MD

Professor, Environmental and Occupational Health

Associate Professor Medicine, Department of Medicine

Associate Professor, Clinical and Translational Science Institute

Contact

100 Technology Drive, Bridgesidepoint Building 1 15219
R-znvy: ynb6@cvgg.rqh
Primary Phone: 967-179-0714


Personal Statement

My research focuses on mechanisms of lung injury that lead to the development of lung fibrosis. In particular, my laboratory has contributed to this field with the development of mouse models of pulmonary fibrosis (silica and bleomycin) and most recently with the concept that bone marrow derived Mesenchymal stem cells (MSCs) are fundamental contributors to the repair of the injured lung. Similarly, my laboratory has characterized the epidemiology of environmentally induced lung disease. Since my arrival to Pittsburgh, I established alliances with grass root organizations to initiate registries and form cohort of subjects exposed to dust (mostly miners) to characterize the impact of pneumoconiosis in the communities of Western Pennsylvania. Subsequently, I contributed to the literature with studies of the prevalence and outcome of silica exposed individuals, and their response to lung transplantation.

My basic science and translational research initiatives led to the demonstration that following the systemic administration of MSC into bleomycin or silica exposed mice these cells are retained in the injured lung and ameliorated the lung injury. Subsequently, my laboratory identified that MSCs exhibit a significant paracrine activity, exerted via secretion of extracellular vesicles and preformed proteins, and regulate innate immunity in the lung.  Thus, MSC produce large amounts of the anti inflammatory cytokine IL1 Receptor antagonist and exosomes that modulate the macrophage production of TNF and inhibit T cell proliferation. My laboratory also studies MSC production of TSG-6 and exosomes as mechanisms that these cells use to ameliorate RV function during the development of pulmonary arterial hypertension in animal models and subjects afflicted by fibrotic lung disease.


In addition, my laboratory identified data indicating that in addition to soluble mediators, MSC release endosomal vesicles (multi vesicular bodies and exosomes) containing mitochondria and micro RNAs. Thus, MSCs can establish intercellular communication to promote genetic exchange and that further contribute to the reprogram of the inflammatory response of activated macrophages in the injured lung. Subsequently, we are conducting pre clinical evaluation of these extracellular vesicles in animal model of lung fibrosis.

Most recent efforts have concentrated in translating these preclinical observations. To that effect I have interacted with Dr. Michael Matthay, an eminent clinical investigator in the field of acute lung injury, to test the efficacy of MSC in subjects afflicted by Adult Respiratory Distress Syndrome (ARDS). This interactions lead Dr. Matthay to designate the University of Pittsburgh as one of the four sites for his START clinical trial to test the safety of well characterized primary human MSCs, manufactured by Dr. David McKenna at the HLBI-sponsored PACT program at the University of Minnesota, in subjects with ARDS requiring mechanical ventilation in whom a 40 percent mortality is expected.

Currently, my laboratory is conducting investigator initiated translational research and we have received support from NHLBI, in the form of an RO1, to conduct a phase I clinical trial testing the safety and efficacy of MSCs on subjects afflicted by pulmonary arterial hypertension as a result of their idiopathic pulmonary fibrosis. We are screening these subjects among populations of patients who are receiving medical care at the Simmons Center for Interstitial Lung Disease (ILD), where I conduct my clinical service and I serve as a liaison between the ILD and transplant services. These funds from NHLBI support the production of clinical grade MSCs by the NHI sponsored PACT program at the University of Minnesota in order to test the safety of these cells in a phase I/II trail as described above.



Education

UNDERGRADUATE:
1976   Instituto Jorge Robledo.  Medellin, Colombia.  Bachelor Science.  

GRADUATE:
1983    Universidad Pontificia Bolivariana.  Medellin, Colombia.  MD

POSTGRADUATE:
1984-1987. Resident in Internal Medicine. 
Department of Medicine
Universidad Pontificia Bolivariana.
Medellin, Colombia. 

1987-1990 Resident in Internal Medicine.                       
Department of Medicine                
Tulane Medical Center
New Orleans, Louisiana

1990-1993 Fellow
Pulmonary and Critical Care Medicine                                                                       University of Texas Health Science Center           
M.D. Anderson Cancer Center                      
Houston, Texas

1991-1993 Post Doctoral Student
Department of Biochemistry (John Olson’s laboratory)
Rice University
Houston, Texas





Teaching

This academic year I will be predominantly involved in teaching stem cell biology and consequently will contribute lectures in the Stem Cell Biology Course (3740) for the multidisciplinary program under direction of Paul Monga, MD.


Study section

Member NHLBI Mentored Clinician and Basic Science Review Committee  Tenure 2014-2019


Selected Publications

Mischler S.E., Cauda E.G., Di Giuseppe, M.,

McWilliams L.J., St. Croix, C., Su. M., Franks, J., and Ortiz LA.  Differential activation of RAW 264.7 macrophages by size-segregated crystalline

silica.  J Occup Med Toxicol. 2016 Dec 15;11:57. doi: 10.1186/s12995-016-0145-2. PMID:

28018477

Boregowda SV., Krishnappa V., Haga CL., Ortiz L.A., and D.G. Phinney.  A clinical Indications Prediction Scale based on TWIST1for Human Mesenchymal Stem Cells. EBioMedicine.  2015 Dec 24;4:62-73. doi: 10.1016/j.ebiom.2015.12.020. eCollection 2016 Feb. PMID: 26981553

Phinney D.G., DiGiuseppe M., Njah J., Sala-Llinas E.,DeLuliis, G., Kaminski N., Shiva S., St. Croix C.M. Stolz D.B., Watkins S.C., Di P.Y., Leikauf GD., Kolls J., Riches DWH., McKenna D., and Ortiz L.A.  Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs.  Nat Commun. 2015 Oct 7;6:8472. doi:
10.1038/ncomms 9472.  PMID: 26442449.

 Rubin J.M., Horowitz J.C., Sisson T.H., Kim K., Ortiz L.A., and Hamilton
J.D.  Ultrasound Strain Measurements for Evaluating Local Pulmonary Ventilation.  IEEE EEE Int Ultrason Symp. 2015 Oct;2015. doi:
10.1109/ULTSYM.2015.0181. PMID: 26635917.

Boregowda S., Krishnappa V., Chambers J.W, LoGrasso P.V, Lai W-T., Ortiz L.A., and D.G. Phinney.  Atmospheric oxygen inhibits growth and differentiation of marrow-derived mouse MSC via a p53 dependent mechanism.  Stem Cells. 2012 May;30(5):975-87. doi: 10.1002/stem.1069. PMID:22367737


Bein, K., Di Giuseppe, M., Mischler, S.E., Ortiz, LA; and Leikauf,
G.D  Surfactant Protein B repression in pulmonary epithelial cells by LPS-stimulated macrophages via cytokines. Am J Respir Cell Mol Biol. 2013 Apr 3. [Epub ahead of print] PMID:23590297

Michael A. Matthay, Piero Anversa, Jahar Bhattacharya, Bruce K. Burnett, Harold A. Chapman, Joshua M. Hare, Derek J. Hei, Andrew M. Hoffman, Stella Kourembanas, David H. McKenna, Luis A. Ortiz, Harald C. Ott, William Tente, Bernard Thébaud, Bruce C. Trapnell, Daniel J. Weiss, Jason X.-J. Yuan, Carol J. Blaisdell.  Cell Therapy for Lung Diseases, Report from an NIH-NHLBI Workshop November 13-14, 2012. Am J Respir Crit Care Med. 2013 May 28. [Epub ahead of print] PMID:23713908

Mischler, S., Cauda, E., DiGiuseppe M., and Ortiz L.A.  A multi-cyclone sampling array for the collection of size-segregated occupational aerosols.  J Occup Environ Hyg. 2013 Dec;10(12):685-93. doi: 10.1080/15459624.2013.818244. PMID: 24195535


Timothy S. Blackwell, Andrew M. Tager, Zea Borok, Bethany B.
Moore,  David A. Schwartz, Kevin J.Anstrom, Ziv Bar-Joseph, Peter Bitterman, Michael R. Blackburn, William Bradford, Kevin K. Brown, Harold A. Chapman, Harold R Collard, Gregory P. Cosgrove,
Robin Deterding, Ramona Doyle, Kevin J. Flaherty, Christine Kim Garcia, James S. Hagood, Craig A. Henke, Erica Herzog, Cory M. Hogaboam, Jeffrey C. Horowitz, Talmadge E. King, Jr., James E. Loyd, William E. Lawson, Clay B. Marsh, Paul W. Noble, Imre Noth, Dean Sheppard, Julie Olsson, Luis A. Ortiz, Thomas G. O’Riordan, Tim D. Oury, Thomas H. Sisson, Ganesh Raghu, Jesse Roman, Patricia J. Sime, Daniel Tschumperlin, Shelia M. Violette, Timothy E. Weaver, Rebecca G. Wells, Eric S.White, Naftali Kaminski, Fernando J. Martinez, Thomas A. Wynn, Victor J. Thannickal and Jerry P. Eu.  NHLBI Workshop Summary: Future Directions in Idiopathic Pulmonary Fibrosis Research An NHLBI Workshop Report.  Am J Respir Crit Care Med. 2013 Oct 25. [Epub ahead of print] PMID: 24160862

Redente E.F., Keith R.C, Janssen W., Henson P.M., Ortiz L.A., Downey G.P., Bratton D.L., and DW. Riches. TNF-a accelerates the resolution of established pulmonary fibrosis in mice by targeting alternatively programmed lung macrophages.  Am J Respir Cell Mol Biol. 2013 Dec 10. [Epub ahead of print] PMID: 24325577


Fazzi F., Winnica D.E., Di Giuseppe M., Njah J., Go K., Sala E., St Croix C.M, Watkins S.C., Tyurin V.A., Phinney D.G., Leikauf G.D., Kagan V.E., and Ortiz, LA. TNFR1/Phox Interaction and TNFR1 Mitochondrial Translocation Thwarts Silica-Induced Pulmonary Fibrosis. The Journal of Immunology.  2014 Apr  15;192(8):3837-46. doi:10.4049/jimmunol.1103516. Epub 2014 Mar 12. PMID: 24623132






Luis A Ortiz
© 2017 by University of Pittsburgh Graduate School of Public Health

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