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Xueqin Gao
  • Department: Linda & Mitch Hart Center for Regenerative and Personalized Medicine

Xueqin Gao,

MD, PhD

Principal Investigator & Program Director of Bone & Cartilage Biology and Tissue Engineering

Education

Tongji Medical University, MD,1986
Shandong Academy of Medical Sciences, MPH,1991
Shandong University, PhD, 2005
Medical College of Wisconsin, Postdoctoral fellow, 2009
University of Pittsburgh, Postdoctoral associate, 2014

Overview of research

Dr. Gao is currently a Principal Investigator and Program Director of Bone and Cartilage Biology and Tissue Engineering at the Linda & Mitch Hart Center for Regenerative and Personalized Medicine (CRPM) at Steadman Philippon Research Institute (SPRI). In Dr. Huard’s CRPM team, Dr. Gao’s goal is to use her expertise in bone and cartilage tissue engineering and biology to develop new therapies to treat orthopaedic injuries and “keep people active.”   Dr. Gao’s research focuses on the following topics:
 
  1. The use of coacervate (in collaboration with Dr. Yadong Wang, Cornell University) to sustain release systems to deliver growth factors and cells for cartilage and bone regeneration.
  2. Use of MRL/MPJ super-healer mice to identify factors that can be used to promote cartilage and bone regeneration.
  3. Elucidate the mechanism and develop new approach for improvement of osteopenia and muscle pathology in muscular dystrophy
  4. Develop microfracture augmentation therapies using losartan, fiestin and other factors for cartilage repair. This area of research has led to several ongoing clinical trials directed by Dr. Huard.

Biography, Training and Honors

Dr. Gao was an assistant professor from May 2015–January 2020 at the Department of Orthopaedic Surgery at the University of Texas Health Science Center and a visiting scientist to Steadman Philippon Research Institute (SPRI) before joining SPRI full-time Jan 28, 2020. She was also an associate member of the Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center and UTHealth in 2018. In 2009, Dr. Gao joined Dr. Huard’s Team in the Department of Orthopaedic Surgery, University of Pittsburgh as a postdoctoral fellow and received extensive training in stem cell biology, gene therapy and bone tissue engineering until April 2015. She has published three first author papers during this time including in Biomaterials. She has won many career awards such as the New Investigator Recognition Award from ORS (2012), AFIRM Career Enrichment Award (2012), Young Investigator Travel Awards from ASBMR (2014) and ASGCT (2014).

Before coming to the United States, Dr. Gao spent 21 years doing biomedical research in China and became a full professor in 2002 in China. She was a director of Biochip Laboratory and Associate Director of Shandon Medicinal and Biotechnological Center, Shandong Academy of Medical Science, where she was in charge of research, graduate student education and international collaboration. She has won many scientific progress awards and holds more than 10 Chinese patents and published 90+ publications in China. She mentored eight master students during this period.

Dr. Gao is an editorial board and peer reviewer for several journals and meeting abstracts reviewer of ORS, ASBMR and ASGCT.

Contributions to Science

Cancer Chemoprevention, Cancer Biology and High-Throughput Technology for Cancer Targets Discovery

I worked on toxicology during master training and have published several papers in prestigious Chinese Journals under the mentorship of Professor Cibin Qiao. After I received my master’s degree in Public Health with a concentration in Toxicology, I moved my direction to cancer research, especially focused on the colorectal cancer chemoprevention and molecular biology as a principal investigator. By using a transplanted sarcoma model and epidemiology and molecular biology, I found that the non-steroid anti-inflammatory drugs (NSAIDs) have cancer prevention effects. I believe that both cancer and inflammation have over-activated cyclooxgenase-2 signaling pathways. I also worked as a professor and master student mentor in team with other investigators, I continued to do research on colorectal cancer biology and established biochip platforms such as cDNA microarray, oligo nucleotide, microarray and protein assays in my lab. I have 9 patents and Science and Technology Awards. Related publications are below.
 
  1. Gao XQ*, Sun S, Sun HB, Sun F, Zhang W, Song S. Nonsteroidal anti-inflammatory drugs and the risk of polyposis, colon carcinoma and rectal carcinoma. Zhong Hua Yu Fang Yi Xue Za Zhi (Chinese Journal of Preventive Medicine). 2002;36(5): 332-335, PMID:12411196, Corresponding author.
  2. Gao XQ, Han JX, Huang HY, Xu ZF, Zhang WD, Zhu B. Identification of the differential expressive metastasis associated genes in 21 rectal cancers by cDNA microarray. World J Gastroenterol 2007;13(3):341-348, PMID:17230600
  3. Gao XQ, Han JX, Huang HY, Song B, Zhu B, Song CZ. Effects of NS398 on metastasis-associated gene expression in a human colon cancer cells detected by cDNA microarray. World J Gastroenterol. 2005;11(28):4337-4343, PMID:1603803
  4. Gao XQ, Han JX, Huang HY, Yan S, Song CZ, Huang HN. Effect of aspirin on metastasis-associated gene expression of ovarian cancers detected by cDNA microarray. Acta Pharmacol Sin. 2004; 25(10): 1327-33, PMID:15456535

Stem Cell, Gene Therapy and Bone Tissue Engineering

Under the mentorship of Dr. Johnny Huard, I received advanced training in this field as a postdoctoral fellow. As a co-investigator of Dr. Huard’s proposals and in collaboration with Dr. Bing Wang, I addressed important questions regarding muscle stem cells and host cells’ contribution to tissue bone regeneration. I found that murine muscle stem cells not only have directly contributed to the new regenerated bone tissues, but they also attract host cells such as inflammatory cells and vascular endothelial cells to coordinate to form new functional bone tissues. COX-2 is one of the genes that mediated these donor and host interactions. I have optimized gene therapy vectors and growth factors and found that human muscle-derived stem cells are more efficient to regenerate bone when using lentiviral vector and BMP2 as growth factors compared to retro-viral vector and BMP4. They are as efficient as human bone marrow stem cells in terms of bone regeneration when transduced with Lenti-BMP2. I found that the bone regeneration of human muscle-derived stem cells was not affected by the donor’s age, but impaired by the host’s age.
 
  1. Gao X, Lu A, Tang Y, Schneppendahl J, Liebowitz AB, Scibetta AC, Morris ER, Cheng H, Huard C, Amra S, Wang B, Hall MA, Lowe WR, Huard J. Influences of donor and host age on human muscle-derived stem cell-mediated bone regeneration. Stem Cell Res Ther. 2018 Nov 21;9(1):316. PMID:30463597
  2. Gao X, Usas A, Lu A, Kozemchak A, Tang Y, Poddar M, Sun X, Cummins JH, Huard J. Cyclooxygenase-2 deficiency impairs muscle-derived stem cell-mediated bone regeneration via cellular autonomous and non-autonomous mechanisms. Hum Mol Genet. 2016 Aug 1;25(15):3216-3231. PMID:27354351.
  3. Gao X, Usas A, Tang Y,Lu A,Tan J, Schneppendahl J, Kozemchek AM, Wang B, Tuan RS, Huard J. A comparison of bone regeneration with human mesenchymal stem cells and muscle derived stem cells and with critical role of BMP. Biomaterials, 2014 Aug;35(25):6859-70. PMID: 24856105
  4. Gao X, Usas A, Proto JD, Lu A, Cummins JH, Chen CW, Huard J. Role of donor and host cells in muscle derived stem cell mediated bone repair: Differentiation versus paracrine effects. FASEB J. 2014 Aug;28 (8):3792-809. PMID: 24843069

Bone Biology

I also work on bone biology of muscular dystrophin mice. I found Dystrophin/Utrophin double knockout mice exhibit osteopenia and delayed fracture healing, which are related with muscle damage. I also mentored a postdoc that discovered that the super-healer mice have higher bone mass. These models allowed us to discover new targets for potential treatment of osteoporosis and bone defects. These projects are ongoing.
 
  1. Gao X, Tang Y, Amra S, Sun X, Cui Y, Cheng H, Wang B, Huard J. Systemic Investigation of Bone and Muscle Abnormalities in Dystrophin/Utrophin Double Knockout Mice During Postnatal Development and the Mechanisms. Hum Mol Genet. 2019 May 15;28(10):1738-1751. doi: 10.1093/hmg/ddz012.PMID:30689868
  2. Sun X, Gao X*, Deng Z, Zhang L, McGilvray K, Gadomski BC, Amra S, Bao G, Huard J. High Bone Microarchitecture, Strength, and Resistance to Bone Loss in MRL/MpJ Mice Correlates With Activation of Different Signaling Pathways and Systemic Factors. FASEB J. 2020 Jan;34(1):789-806.PMID:31914651, Co-corresponding author.
  3. Gao X, Sun X, Amra S, Cui Y, Deng Z, Cheng H, Zhang GW, Huard CA, Wang B, Huard J. Impaired  bone defect and fracture healing in dystrophin/utrophin double-knockout mice and the mechanism. Am J Transl Res. 2020 Sep 15;12(9):5269-5282. eCollection 2020.PMID: 33042418

Cartilage Tissue Engineering and Regeneration

After I moved to the University of Texas as an assistant professor, I have led Dr. Huard’s bone and cartilage group. I completed Dr. Huard’s R21 project, “The use of coacervate technology as a new drug delivery system for muscular skeletal tissue repair.” I also made great contributions in developing new therapies using a microfracture (aka bone marrow stimulation) model in rabbits and found that oral losartan, in combination with BMS, enhanced hyaline cartilage repair. Intra-articular cartilage injection of losartan and vascular endothelial cells growth factor (VEGF) also represent a new microfracture enhancement therapy. These findings have led to two clinical trials funded by the Department of Defense (DoD), led by Dr. Johnny Huard and other clinical doctors.
 
  1. Gao X, Cheng H, Awada H, Tang Y, Amra S, Lu A, Sun X, Lv G, Huard C, Wang B, Bi X, Wang Y, Huard J. A Comparison of BMP2 Delivery by Coacervate and Gene Therapy for Promoting Human Muscle-Derived Stem Cell-Mediated Articular Cartilage Repair. Stem Cell Res Ther. 2019 Nov 26;10(1):346. doi: 10.1186/s13287-019-1434-3.PMID:31771623
  2. Utsunomiya H, Gao X*, Cheng H, Deng Z, Nakama G, Mascarenhas R, Goldman JL, Ravuri SK, Arner JW, Ruzbarsky JJ, Lowe WR, Philippon MJ, Huard J.Intra-articular Injection of Bevacizumab Enhances Bone Marrow Stimulation-Mediated Cartilage Repair in a Rabbit Osteochondral Defect Model. Am J Sports Med. 2021,PMID: 33979242, *Co-first author
  3. Logan CA, Gao X*, Utsunomiya H, Scibetta AC, Talwar M, Ravuri SK, Ruzbarsky JJ, Arner JW, Zhu D, Lowe WR, Philippon MJ, Huard J. The beneficial effect of intra-articular injection of losartan on the microfracture mediated-cartilage repair is dose dependent. Am J Sports. Med, 2021, In press,*Co-first author
  4. Utsunomiya H, Gao X, Deng Z, Cheng H, Nakama G, Scibetta AC, Ravuri SK, Goldman JL, Lowe WR, Rodkey WG, Alliston T, Philippon MJ, Huard J. Biologically Regulated Marrow Stimulation by Blocking TGF-β1 With Losartan Oral Administration Results in Hyaline-like Cartilage Repair: A Rabbit Osteochondral Defect Model. Am J Sports Med. 2020 Mar;48(4):974-984. PMID: 32027515
Cartilage Biology

To develop new therapy for cartilage repair and regeneration, understanding the basic cartilage biology is important. I have used a super-healing mouse model MRL/MpJ to investigate the mechanism and identify factors for cartilage repair.
 
  1. Gao X, Patwa AN, Deng Z, Utsunomiya H, Grinstaff  MW, Ruzbarsky JJ, Snyder BD, Ravuri S, Philippon MJ, Huard J. Influence of fixation on CA4+ contrast enhanced microCT of articular cartilage and subsequent feasibility for histological evaluation. Am J Transl. Res, 2021 June, In press
  2. Deng Z, Gao X*, Sun X, Amra S, Lu A, Cui Y, Eltzschig HK, Lei G, Huard J. Characterization of articular cartilage homeostasis and the mechanism of superior cartilage regeneration of MRL/MpJ mice. FASEB J. 2019 Aug;33(8):8809-8821.PMID:31042406, Co-corresponding author.
  3. Scibetta AC, Morris ER, Liebowitz AB, Gao X*, Lu A, Philippon MJ, Huard J. Characterization of the chondrogenic and osteogenic potential of male and female human muscle-derived stem cells: Implication for stem cell therapy. J Orthop Res. 2019 Jun;37(6):1339-1349. Doi: 10.1002/jor.24231. Epub 2019 Feb 21.PMID: 30667562, Co-corresponding author.

Current and past grants

1R01 AR077045-01A1                PI: Dr. Naoki Nakayama                    4/1/2021-3/31/2026
Project title: Articular Cartilage Tissue Engineering with Human Pluripotent Stem Cells
Role: Co-investigator

NIH 1UG3AR077748-01              PI: Dr. Johnny Huard                         8/1/2020 – 7/31/25
Project title: The Use of Senolytic and Anti-Fibrotic Agents to Improve the Beneficial Effect of Bone Marrow Stem Cells for Osteoarthritis.
Role: Basic biologist

5 R01 AR065445                           PI: Dr. Johnny Huard                        05/06/14-4/30/21
Project title:  Bone abnormalities & healing defect in muscular dystrophy
Role: Co-investigator

MTF Young Investigator Grant     PI: Dr. Ryan J. Warth                    07/01/17-6/30/18  
Project title: Can we improve meniscal healing in the avascular zone? fibrin clot augmentation with stem cells and anti-fibrotic drugs
Role: Co-investigator

5R21AR066206               PI: Dr. Johnny Huard                 04/04/14-3/31/17
Project title: The use of coacervate technology as a new drug delivery system for muscular skeletal tissue repair.
Role: Co-investigator

5 R01 DE013420              PI:  Johnny Huard                   09/01/09-08/31/12
Project title: Muscle-based tissue engineering to improve bone healing.
Role: Co-Investigator

Complete List of Published Work in PUBMED and Chinese database:
Pubmed 21 papers
Pubmed 9 papers
Chinese database 88 paper
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