Center for Regenerative Medicine
Rhode Island Hospital
Warren Alpert Medical School of Brown University
One Hoppin Str. CORO Bldg 402C
Providence, RI 02903
Olin Liang, PhD
Dr. Olin Liang is currently an Assistant Professor at the Center for Regenerative Medicine at Rhode Island Hospital and Warren Alpert Medical School of Brown University. Dr. Liang completed his PhD thesis in Microbiology at the Karolinska Institute and Lund University in Sweden, and received postdoctoral training at Max Planck Institute in Germany. He was a Staff Scientist at Boston Children’s Hospital and an Instructor of Pediatrics at Harvard Medical School before he joined Rhode Island Hospital and Brown University in 2013.
Dr. Liang’s research interests are studying the mechanisms of pulmonary hypertension, and the therapeutic potential of genetically modified stem cells in pulmonary hypertension, as well as hematopoietic stem cell biology. Previously, Dr. Liang was awarded a NIH-National Research Service Award (NRSA) to investigate the role of lipid phosphatase SHIP in hematopoietic niche formation and maintenance. This study was the first to establish a hematopoietic bone marrow microenvironment reconstitution system to functionally examine specific cell types in hematopoietic niches. It also suggests that selective inhibition of SHIP in patients may improve treatment outcome of devastating blood diseases by targeting the aberrant bone marrow microenvironment. Recently, Dr. Liang received a second NIH-NRSA and a pilot project grant from the CardioPulmonary Vascular Biology COBRE to study a developmental process called endothelial to hematopoietic transition and its potential role in pulmonary hypertension.
In addition to establishing his research credentials, which include numerous original publications in leading scientific journals, Dr. Liang actively participates in undergraduate and graduate student education, as well as in clinical and research fellow training.
The Role of Endothelial to Hematopoietic Transition in Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a severe and frequently fatal disease that is either idiopathic, familial or secondary. The hallmark of PAH is the development of elevated pulmonary vascular resistance, leading to increased right ventricular pressure and ultimately progression to heart failure and death. Although current intervention offers relief from symptoms and prolonged survival, there is no cure for this disease. Improving treatment strategies requires a thorough understanding of the molecular mechanisms underlying the pathophysiology of PAH despite the multifactorial nature of the disease. The primary objective of this pilot proposal is to determine whether a developmental process called endothelial to hematopoietic transition (EHT) may play a role in the pathogenesis of PAH. To test this hypothesis, we propose the following specific aims: Aim 1: To identify potential endothelial to hematopoietic transition in pulmonary arterial hypertension by lineage tracing. Aim 2: To test whether blocking endothelial to hematopoietic transition can alleviate pulmonary arterial hypertension. Successful completion of this pilot study will provide significant preliminary data for a NIH research project grant (R01) application, where molecular mechanisms of EHT can be further investigated and potential therapeutic targets for PAH can be identified. Our long-term goal is to gain a better understanding of potential pathogenic mechanisms leading to PAH, which may provide novel therapies for treatment and prevention of this devastating cardiopulmonary vascular disease.
1. Liang OD, Lu J, Nombela-Arrieta C, Zhong J, Zhao L, Pivarnik G, Mondal S, Chai L, Silberstein LE, Luo HR. Deficiency of lipid phosphatase SHIP enables long-term reconstitution of hematopoietic inductive bone marrow microenvironment. Dev Cell. 2013 May 28;25(4):333-49.
PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/23725762
2. Liang OD, Kleibrink BE, Schuette-Nuetgen K, Khatwa UU, Mfarrej B, Subramaniam M. Green tea epigallo-catechin-galleate ameliorates the development of obliterative airway disease. Exp Lung Res. 2011 Sep;37(7):435-44.
PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/21787235
3. Vergadi E, Chang MS, Lee C, Liang OD, Liu X, Fernandez-Gonzalez A, Mitsialis SA, Kourembanas S. Early macrophage recruitment and alternative activation are critical for the later development of hypoxia-induced pulmonary hypertension. Circulation. 2011 May 10;123(18):1986-95.
PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/21518986
4. Liang OD, Mitsialis SA, Chang MS, Vergadi E, Lee C, Aslam M, Fernandez-Gonzalez A, Liu X, Baveja R, Kourembanas S. Mesenchymal stromal cells expressing heme oxygenase-1 reverse pulmonary hypertension. Stem Cells. 2011 Jan;29(1):99-107.
PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/20957739
5. Fredenburgh LE, Liang OD, Macias AA, Polte TR, Liu X, Riascos DF, Chung SW, Schissel SL, Ingber DE, Mitsialis SA, Kourembanas S, Perrella MA. Absence of cyclooxygenase-2 exacerbates hypoxia-induced pulmonary hypertension and enhances contractility of vascular smooth muscle cells. Circulation. 2008 Apr 22;117(16):2114-22.
PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/18391113
6. Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, Noiseux N, Zhang L, Pratt RE, Ingwall JS, Dzau VJ. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med. 2005 Apr;11(4):367-8.
PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/15812508
Sharon Rounds, MD
Department of Medicine
Providence VA Medical Center