Research

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Zhi-Jian Liu, PhD

Zhu Jian Liu, PhD
Department:
Medicine Research
Division
Newborn Medicine Research
Hospital Title:
Associate Scientific Researcher
Academic Title:
Instructor in Pediatrics, Harvard Medical School
Research Focus Area:
Thrombopoiesis and Platelets in Development
Contact:
617-919-2339
Contact Via Email
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Research Overview

Dr. Liu’s research is focused on developmental differences of platelets and thrombopoiesis, with the aim of advancing our understanding of neonatal thrombocytopenia.  Previously, it was believed that fetal and neonatal megakaryocytes were incomplete in maturation due to their small size and their rapidly-growing progenitors. Dr. Liu's first accomplishment in this area demonstrated a unique uncoupling of enodomitosis and cytoplasmic maturation during fetal/neonatal megakaryopoiesis, which resulted in generating small, but fully mature, megakaryocytes. This finding was highlighted in an "Inside Blood" editorial review. His second research article revealed that prolonging the lifespan of platelets provides a major mechanism for matching platelet mass expansion during fetal/neonatal development. These findings introduced a new paradigm:  the rapid expansion of blood volume predisposes fetuses and neonates to develop severe thrombocytopenia. Dr. Liu is further exploring the mechanisms that regulate such a characteristic process of fetal/neonatal thrombopoiesis. His major focus is on the developmental difference in expression of microRNA let7B and its role in thrombopoiesis. 

Dr. Liu is also working on the influences of maternal antibodies against human platelet antigen-1A (HPA-1A) on megakaryopoiesis. Maternal HPA-1A antibodies account for over 80% of fetal/neonatal alloimmune thrombocytopenia (F/NAIT), with severe sequela.  Intravenous immunoglobulin (IVIG) treatment is the therapy of choice for F/NAIT. However, over 20% of cases are nonresponsive to IVIG treatment. His study showed that the majority of maternal serum samples can suppress megakaryopoiesis in vitro by inducing cell death of immature megakaryocytes. His results also suggest an inverted correlation between the suppression of in vitro megakaryopoiesis and the outcomes of IVIG treatment indicated by postnatal peripheral platelet count. Dr. Liu's following studies will investigate the possible approaches to prevent megakaryocyte death caused by maternal antibodies, with a goal of improving the therapeutic outcomes of IVIG treatment. 


About Zhi-Jian Liu

Zhi-Jian Liu received his Ph.D. degree in Pharmaceutical Sciences (Pharmacology) at the University of South Carolina, College of Pharmacy. He finished his first postdoctoral training in gene therapy at Columbia University Medical Center. In 2008, he joined Dr. Martha Sola-Visner’s group at Boston Children’s Hospital, Division of Newborn Medicine and Harvard Medical School, Department of Pediatrics, as a postdoctoral research fellow. In 2011, he was awarded a “William Randolph Hearst Foundation Award for Pre- and Peri-natal Medicine” fellowship for his research on fetal/neonatal alloimmune thrombocytopenia. In 2012, he was appointed staff scientist and Instructor in Pediatrics at Boston Children’s Hospital and Harvard Medical School. 


Key Publications

Liu Zhi-Jian, Hoffmeister K, Hu Z, Mager DE, Ait-Oudhia S, Debrincat MA, Pleines I, Josefsson EC, Kile BT, Italiano J Jr, Ramsey H, Grozovsky R, Veng-Pedersen P, Chavda C, Sola-Visner M. Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan. Blood. 2014 Mar 5. [Epub ahead of print]

Ferrer-Marin F, Gutti R, Liu Zhi-Jian, Sola-Visner M. MiR-9 contributes to the developmental differences in CXCR-4 expression in human megakaryocytes. J Thromb Haemost. 2014; 12(2):282–285.

Cooper ST, Richters KE, Melin TE, Liu Zhi-Jian, Hordyk PJ, Benrud RR, Geiser LR, Cash SE, Simon Shelley C, Howard DR, Ereth MH, Sola-Visner MC. The hibernating 13-lined ground squirrel as a model organism for potential cold storage of platelets. Am J Physiol Regul Integr Comp Physiol. 2012 May 15;302(10):R1202-8.

Liu Zhi-Jian, Sola-Visner M. Neonatal and adult megakaryopoiesis. Curr Opin Hematol. 2011 Sep;18(5):330-7.

Liu Zhi-Jian, Italiano J, Ferrer-Marin1, Gutti R, Bailey M, Poterjoy B, Rimsza L, and Sola-Visner MC [2011]. Developmental differences in megakaryocytopoiesis are associated with up-regulated Tpo signaling through mTOR and elevated levels of full length GATA-1 in neonatal megakaryocytes.  Blood. 2011 Apr 14;117(15):4106-17. (“Inside Blood” comment: Blood 117:3940-1).

Ferrer-Marin F, Liu Zhi-Jian, Gutti R, Sola-Visner M. Neonatal thrombocytopenia and megakaryocytopoiesis. Semin Hematol. 2010 Jul;47(3):281-8.

Sallmon H, Gutti R, Ferrer-Marin F, Liu Zhi-Jian, Sola-Visner MC.  Increasing platelets without transfusions: Is it time to introduce novel thrombopoietic agents in neonatal care? Journal of Perinatology 2010 30:765-769.

Publications

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  1. Shi DS, Smith MC, Campbell RA, Zimmerman PW, Franks ZB, Kraemer BF, Machlus KR, Ling J, Kamba P, Schwertz H, Rowley JW, Miles RR, Liu ZJ, Sola-Visner M, Italiano JE, Christensen H, Kahr WH, Li DY, Weyrich AS. Proteasome function is required for platelet production. J Clin Invest. 2014 Sep; 124(9):3757-66.
  2. Liu ZJ, Hoffmeister KM, Hu Z, Mager DE, Ait-Oudhia S, Debrincat MA, Pleines I, Josefsson EC, Kile BT, Italiano J, Ramsey H, Grozovsky R, Veng-Pedersen P, Chavda C, Sola-Visner M. Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan. Blood. 2014 May 29; 123(22):3381-9.
  3. F. Ferrer-Marin, R. Gutti, Z.-J. Liu M. Sola-Visner . Journal of Thrombosis and Haemostasis. MiR-9 contributes to the developmental differences in CXCR-4 expression in human megakaryocytes. 2014; 12(2):282–285.
  4. Cooper ST, Richters KE, Melin TE, Liu ZJ, Hordyk PJ, Benrud RR, Geiser LR, Cash SE, Simon Shelley C, Howard DR, Ereth MH, Sola-Visner MC. The hibernating 13-lined ground squirrel as a model organism for potential cold storage of platelets. Am J Physiol Regul Integr Comp Physiol. 2012 May 15; 302(10):R1202-8.
  5. Liu ZJ, Sola-Visner M. Neonatal and adult megakaryopoiesis. Curr Opin Hematol. 2011 Sep; 18(5):330-7.
  6. Liu ZJ, Italiano J, Ferrer-Marin F, Gutti R, Bailey M, Poterjoy B, Rimsza L, Sola-Visner M. Developmental differences in megakaryocytopoiesis are associated with up-regulated TPO signaling through mTOR and elevated GATA-1 levels in neonatal megakaryocytes. Blood. 2011 Apr 14; 117(15):4106-17.
  7. Sallmon H, Gutti R, Ferrer-Marin F, Liu ZJ, Sola-Visner MC. . Increasing platelets without transfusions: Is it time to introduce novel thrombopoietic agents in neonatal care?. Journal of Perinatology. 2010; 12(30):765-769.
  8. Lebedeva IV, Emdad L, Su ZZ, Gupta P, Sauane M, Sarkar D, Staudt MR, Liu SJ, Taher MM, Xiao R, Barral P, Lee SG, Wang D, Vozhilla N, Park ES, Chatman L, Boukerche H, Ramesh R, Inoue S, Chada S, Li R, De Pass AL, Mahasreshti PJ, Dmitriev IP, Curiel DT, Yacoub A, Grant S, Dent P, Senzer N, Nemunaitis JJ, Fisher PB. mda-7/IL-24, novel anticancer cytokine: focus on bystander antitumor, radiosensitization and antiangiogenic properties and overview of the phase I clinical experience (Review). Int J Oncol. 2007 Nov; 31(5):985-1007.
  9. You S, Ohmori M, Peña MM, Nassri B, Quiton J, Al-Assad ZA, Liu L, Wood PA, Berger SH, Liu Z, Wyatt MD, Price RL, Berger FG, Hrushesky WJ. Developmental abnormalities in multiple proliferative tissues of Apc(Min/+) mice. Int J Exp Pathol. 2006 Jun; 87(3):227-36.
  10. Liu ZJ, Lee WJ, Zhu BT. Selective insensitivity of ZR-75-1 human breast cancer cells to 2-methoxyestradiol: evidence for type II 17beta-hydroxysteroid dehydrogenase as the underlying cause. Cancer Res. 2005 Jul 1; 65(13):5802-11.
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  12. Han GZ, Liu ZJ, Shimoi K, Zhu BT. Synergism between the anticancer actions of 2-methoxyestradiol and microtubule-disrupting agents in human breast cancer. Cancer Res. 2005 Jan 15; 65(2):387-93.
  13. Liu ZJ, Zhu BT. Concentration-dependent mitogenic and antiproliferative actions of 2-methoxyestradiol in estrogen receptor-positive human breast cancer cells. J Steroid Biochem Mol Biol. 2004 Mar; 88(3):265-75.
  14. Ferrer-Marin F, Liu ZJ, Gutti R, Sola-Visner M. Neonatal thrombocytopenia and megakaryocytopoiesis. Semin Hematol. 2010 Jul; 47(3):281-8.
  15. Liu ZJ, Bussel JB, Lakkaraja M, Ferrer-Marin F, Ghevaert C, Feldman HA, McFarland JG, Chavda C, Sola-Visner M. Suppression of in vitro megakaryopoiesis by maternal sera containing anti-HPA-1a antibodies. Blood. 2015 Sep 3; 126(10):1234-6.
  16. Jabara HH, Boyden SE, Chou J, Ramesh N, Massaad MJ, Benson H, Bainter W, Fraulino D, Rahimov F, Sieff C, Liu ZJ, Alshemmari SH, Al-Ramadi BK, Al-Dhekri H, Arnaout R, Abu-Shukair M, Vatsayan A, Silver E, Ahuja S, Davies EG, Sola-Visner M, Ohsumi TK, Andrews NC, Notarangelo LD, Fleming MD, Al-Herz W, Kunkel LM, Geha RS. A missense mutation in TFRC, encoding transferrin receptor 1, causes combined immunodeficiency. Nat Genet. 2016 Jan; 48(1):74-8.
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