Liping Xiao, MD, PhD
Graduate Student, Psychiatry, UConn Health (Affiliate)
I completed post-doctoral training at the University of Connecticut Health Center (UCHC). I am an American Society for Bone and Mineral Research (ASBMR) young investigator award winner and I have made several oral presentations at ASBMR on musculoskeletal research.
As a student in the Master of Science in Clinical and Translational Research at UCHC, I became interested in the studies that use Valproic acid (VPA) to improve behavioral disturbance in Huntington’s disease (HD) patients. VPA is a widely used antiepileptic drug, which has been shown to be neuroprotective. VPA produces beneficial effects in transgenic HD mouse model, However, when VPA was tested in HD patients, there were reports of either some improvement in hyperkinesia or no clinical improvement, in two open-label case series of HD. This is possibly because 1) the dosing ranges in patients have been insufficient, 2) the mechanisms that regulating effect of VPA in HD animal model cells are substantially different from those in human HD neurons in vivo. VPA is also clinically helpful in the treatment of impulsivity and irritability in HD patients (unpublished observations, C. Drazinic who is my mentor). Together, these observations suggest that VPA may have a neuroprotective effect in HD, and therefore, may slow progression of disease, but more rigorous studies need to be performed.
For the InCHIP pilot grant, we plan to provide VPA treatment in 6 patients with HD and irritability for six months, and measure behavioral and neurologic effects by standard questionnaires and clinical assessments recorded by video. We will also obtain peripheral blood to measure VPA levels and differences in expression profiles of Huntington and other genes. We will also explore the effects of VPA on expression of huntingtin and other associated proteins in pluripotent stem cells possessing the huntingtin mutation and their controls.
Hebei Medical University, Shijiazhuang, Hebei, China. M.D 1989 Medicine
Tianjin Medical University, Tianjin, China Ph.D. 2001 Endocrinology & Metabolism
University of Connecticut Health Center, Farmington, CT, USA Master 12/2013, Neuropsychiatry
1. Xiao L, Liu P, Sobue T, Lichtler A, Coffin JD, Hurley MM (2003) Effect of over-expressing fibroblast growth factor 2 protein isoforms in osteoblastic ROS 17/2.8 cells. J Cell Biochem. 89:1291-1301
2. Xiao L, Naganawa T, Obugunde E, Gronowicz G, Ornitz DM, Coffin JD, Hurley MM. (2004) The transcription factor STAT-1 controls Postnatal Bone Formation by Regulating Fibroblast Growth Factor Signaling in Osteoblasts. J Biol Chem 279, 27743-27752. PMID:15073186
3. Sobue T, Naganawa T, Xiao L, Okada Y, Tanaka Y, Ito M, Okimoto N, Nakamura T, Coffin JD, Hurley MM. (2005). Over-expression of fibroblast growth factor-2 causes defective bone mineralization and osteopenia in transgenic mice. J Cell Biochem. 95(1):83-94
4. Naganawa T, Xiao L, Abogunde E, Sobue T, Kalajzic I, Sabbieti M, Agas D, Hurley MM. (2006) In vivo and in vitro comparison of the effects of FGF-2 null and haplo-insufficiency on bone formation in mice. Biochem Biophys Res Commun. 339(2):490-8. PMID:16298332
5. Hurley MM, Okada Y, Xiao L, Tanaka Y, Ito M, Okimoto N, Nakamura T, Rosen CJ, Doetschman T, JD Coffin. (2006) Impaired bone anabolic response to parathyroid hormone in Fgf2-/- and Fgf2+/- mice. Biochem Biophys Res Commun. 341(4):989-94. PMID:16455048
6. Naganawa T, Xiao L, Coffin JD, Doetschman T, Sabbieti MG, Agas D, Hurley MM. (2008) Reduced expression and function of bone morphogenetic protein-2 in bones of Fgf2 null mice. J Cell Biochem. 103(6):1975-88. PMCID: PMC Journal in Process.
7. Xiao L, Liu P, Li X, Doetschamn T, Coffin JD, Drissi H, Hurley MM (2009) The exported 18kD isoform of FGF2 is a critical determinant of bone mass in mice. J Biol Chem 284(5):3170-3182. PMCID: PMC2631953.
8. Sabbieti MG, Agas D, Xiao L, Marchetti L, Coffin JD, Doetschman T, Hurley MM (2009) Endogenous FGF-2 is critically important in PTH anabolic effects on bone. J Cell Physiol 219:143-151. PMCID: PMC2763338.
9. Fei Y, Xiao L, Hurley MM (2010) Fibroblast growth factor-2 positively regulates expression of activating transcription factor 4 in osteoblasts. Biochem Biophys Res Commun. 391(1):335-339. PMID: 19913500.
10. Xiao L, Naganawa T, Lorenzo J, Carpenter TO, Coffin JD, Hurley MM (2010) Nuclear isorofms of fibroblast growth factor-2 are novel inducers of hypophosphatemia via modulation of FGF23 and Klotho. J Biol Chem. 285(4):2834-2846. PMID: 19933269.
11. Sabbieti MG, Agas D, Marchetti L, Santoni G, Amantini C, Xiao L, Menghi G, Hurley MM.(2010). Signaling pathways implicated in PGF2alpha effects on Fgf2+/+ and Fgf2-/- osteoblasts. J Cell Physiol. 224(2):465-74. PMID: 20432442
12. Xiao L, Sobue T, Esliger A, Kronenberg MS, Coffin JD, Doetschman T, Hurley MM. (2010) Disruption of the Fgf2 gene activates the adipogenic and suppresses the osteogenic program in mesenchymal marrow stromal stem cells. Bone. 47(2):360-70. PMID: 20510392.
13. Fei Y, Xiao L, Hurley MM. (2011). The impaired bone anabolic effect of PTH in the absence of endogenous FGF2 is partially due to reduced ATF4 expression.. Biochem Biophys Res Commun. 412(1): 160-4. PMID: 21806973.
14. Fei Y, Xiao L, Doetschman T, Coffin DJ, Hurley MM. (2011). Fibroblast growth factor 2 stimulation of osteoblast differentiation and bone formation is mediated by modulation of the wnt signaling pathway. J Biol Chem. 286(47):40575-83. PMID:21987573
15. Xiao L, Esliger A, Hurley MM. (2012). Nuclear FGF2 isoforms inhibit bone marrow stromal cell mineralization through FGF23/FGFR/MAPK in vitro. J Bone Miner Res. Jul 26. [Epub ahead of print]. PMID:22836867
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