Dr. Xu's research interest is in defining the molecular mechanism by which activation of p90RSK prolongs cardiac repolarization and plays an important role in the development of cardiac arrhythmias. His clinical translational research involves determining oncoportein expression patterns in malignant neoplasms, in particular in lung cancer, and identifying the useful biomarkers for diagnosis and prognosis.

Qualifications

M.D., Soochow University Medical School, China 1987
Ph.D., Cardiac Physiology, Soochow University Medical School, China 1993
Postdoctoral Fellow, Molecular Biology & Pharmacology, Washington University School of Medicine 1993-99
Resident in Anatomic Pathology, Washington University School of Medicine 1999-2001; Resident and Research Fellow 2001-2002; Resident 2002-03
Fellow, Armed Forces Insitute of Pathology 2003-04
Board Certified, American Board of Pathology

Professional Activities

NIH Cardiovascular Training Grant 1997-99 and 2001-02

Research Overview

Cardiac arrhythmias remain a major health problem, causing at least 250,000 deaths annually in the United States. Dr. Xu lab is focused on elucidating molecular signaling pathways involving the development of cardiac arrhythmias so that therapeutic targets for treatment and/or prevention can be identified. p90 ribosomal S6 kinase (p90RSK) is activated in cardiomyopathies caused by conditions such as ischemia/reperfusion injury and diabetes mellitus in which prolongation of cardiac repolarization and frequent arrhythmias are common. In his lab, they have been exploiting a sophisticated combination of biochemical, electrophysiological and molecular techniques to define the molecular mechanisms by which activation of p90RSK prolongs cardiac repolarization. Recent studies in his lab indicate that p90RSK activation is critical for reactive oxygen species-mediated inhibition of voltage-gated K+ channel (I_to,f and I_Kslow1) activity and leads to prolongation of cardiac repolarization.

Ongoing studies in Dr. Xu lab are focused on defining the functional roles of two delayed rectifier I_Kr and I_Ks channel modulation by p90RSK in the development of cardiac arrhythmias and determining if perturbing p90RSK signaling reduces frequency of arrhythmias induced by cardiac pacing in animals with cardiac ischemia/reperfusion injury and diabetic cardiomyopathy.

Research Office and Laboratory:

Aab Cardiovascular Research Institute

University of Rochester School of Medicine and Dentistry

211 Bailey Rd., Box 679, West Henrietta, NY 14586

Office Phone: (585) 276-9796

Lab Phone: (585) 276-9844

Publications

Li L, Xu H, Spaulding BO, Cheng L, Simon R, Yao JL, di'Sant Agnese PA, Bourne PA, Huang J. Expression of RNA-binding protein IMP3(KOC) in benign urothelium and urothelial tumors. Hum Pathol 2008 Jun 9. [Epub ahead of print]

Lester T, Xu H. Malignant pleural mesothelioma with osseousmetastases and pathologic fracture of femoral neck: a case report. Appl Histochem Mol Morphol 2008 Jun 20. [Epub ahead of print]

Wagner D, Bourne PA, Yang Q, Goldman BI, Lewis JS, Xu H. Unusual features of malignant pleural mesothelioma metastatic to the mediastinal lymph nodes. Applied Immunohistochemistry and Molecular Morphology. 2008 May;16(3):301-7.

Pryor JG, Bourne PA, Yang Q, Spaulding BO, Scott GA, Xu H. IMP3 is a progression marker in malignant melanoma. Modern Pathology 2008 Apr;21(4):431-7.

Lu Z, Abe J, Taunton J, Lu Y, Shishido T, McClain C, Yan C, Xu SP, Spangenberg TM, Xu H. Reactive Oxygen Species-Induced Activation of p90 Ribosomal S6 Kinase Prolongs Cardiac Repolarization Through Inhibiting Outward K+ Channel Activity . Circ Res 2008 Jul 3 [ePub ahead of print]

Hanley KZ, Facik MS, Bourne PA, Yang Q, Spaulding BO, Bonfiglio TA, Xu H. Utility of anti-L523S antibody in the diagnosis of benign and malignant serous effusions. Cancer 2008 Feb 25;114(1):49-56.

Lim JH, Jono H. Koga T, Woo CH, Ishinaga H, Bourne P, Xu H, Ha UH, Xu H, Li JD. Tumor suppressor CYLD acts as a neative regulator for non-typeable Haemophilus influenza-induced inflammation in the middle ear and lung of mice. PLoS ONE 2007 Oct 10;2(10):e1032.

Miyamoto H, Molena DA, Schoeniger LO, and Xu H. Solitary fibrous tumor of the pancreas: a case report. International Journal of Surgical Pathology. 2007 July; 15(3) 311-314.

LaPoint RJA, Bourne PA, Wang HL, Xu H. Coexpression of c-kit and bcl-2 in small cell carcinoma and large cell neuroendocrine carcinoma of the lung. Applied Immunohistochemistry and Molecular Morphology. 2007 Dec;15(4):401-6 .

Lim JH, Stirling B, Derry J, Koga T, Jono H, Woo CH, Xu H, Bourne P, Ha UH, Ishinaga H, Xu H, Andalibi A, Feng XH, Zhu H, Huang Y, Zhang W, Weng X, Yan C, Yin Z, Briles DE, Davis RJ, Flavell RA, Li JD. Tumor suppressor CYLD regulates acute lung injury in lethal Streptococcus pneumoniae infections. Immunity. 2007 Aug;27(2):349-60.

Yan C, Ding B, Shishido T, Woo CH, Itoh S, Jeon KI, Liu W, Xu H, McClain C, Molina CA, Blaxall BC, Abe J. Activation of extracellular signal-regulated kinase 5 reduces cardiac apoptosis and dysfunction via inhibition of a phosphodiesterase 3A/inducible cAMP early repressor feedback loop. Circ Res. 2007 Mar 2;100(4):510-9.

Ishinaga H, Jono H, Lim JH, Kweon SM, Xu H, Ha UH, Xu H, Koga T, Yan C, Feng XH, Chen LF, Li JD. TGF-beta induces p65 acetylation to enhance bacteria-induced NF-kappaB activation. EMBO J. 2007 Feb 21;26(4):1150-62.

Simon R, Bourne PA, Yang Q, Spaulding BO, di Sant'Agnese PA, Wang HL, Xu H. Extrapulmonary small cell carcinomas express K homology domain containing protein overexpressed in cancer, but carcinoid tumors do not. Hum Pathol. 2007 Aug;38(8):1178-83. Epub 2007 May 22.

Xu H, Bourne PA, Spaulding BO, Wang HL. High-grade neuroendocrine carcinomas of the lung express K homology domain containing protein overexpressed in cancer but carcinoid tumors do not. Hum Pathol. 2007 Apr;38(4):555-63.

Hameed O, Xu H, Saddeghi S, Maluf H. Hepatoid carcinoma of the pancreas: a case report and literature review of a heterogeneous group of tumors. Am J Surg Pathol. 2007 Jan;31(1):146-52.

Wagner D, Joseph J, Huang J, Xu H. Malakoplakia of the prostate on needle core biopsy: a case report and review of the literature. Int J Surg Pathol. 2007 Jan;15(1):86-9.

Shah AP, Xu H, Sime PJ, Trawick DR. Severe airflow obstruction and eosinophilic lung disease after Stevens-Johnson syndrome. Eur Respir J. 2006 Dec;28(6):1276-9.

Bhagwat SP, Gigliotti F, Xu H, Wright TW. Contribution of T cell subsets to the pathophysiology of Pneumocystis-related immunorestitution disease. Am J Physiol Lung Cell Mol Physiol. 2006 Dec;291(6):L1256-66.

Guo W, Jung WE, Marionneau C, Aimond F, Xu H, Yamada KA, Schwarz TL, Demolombe S, Nerbonne JM. Targeted Deletion of Kv4.2 Eliminates Ito,f and Results in Electrical and Molecular Remodeling, With No Evidence of Ventricular Hypertrophy or Myocardial Dysfunction. Circ Res. 2005 Dec 9;97(12):1342-1350. Epub 2005 Nov 17.

Ding B, Abe J, Wei H, Xu H, Che W, Aizawa T, Liu W, Molina CA, Sadoshima J, Blaxall BC, Berk BC, Yan C. A positive feedback loop of phosphodiesterase 3 (PDE3) and inducible cAMP early repressor (ICER) leads to cardiomyocyte apoptosis. Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14771-6. Epub 2005 Sep 26.

Chiu HC, Kovacs A, Blanton RM, Han X, Courtois M, Weinheimer CJ, Yamada KA, Brunet S, Xu H, Nerbonne JM, Welch MJ, Fettig NM, Sharp TL, Sambandam N, Olson KM, Ory DS, Schaffer JE. Transgenic expression of fatty acid transport protein 1 in the heart causes lipotoxic cardiomyopathy. Circ Res. 2005 Feb 4;96(2):225-33. Epub 2004 Dec 23. X

Xu, H, Lu, D. EL-Mofty and Wang, H. Metachronous squamous cell carcinomas evolving from independent oropharyngeal and pulmonary squamous papillomas: associated with human papillomavirus 11 and lack of aberrant p53, Rb and p16 protein expression. Human Pathology. 2004; 11:1419-22.

Okamato, R, Xu, H, Kouchoukos, N, Moon, MR and Sundt, TM. The influence of medical properties on wall stress and ditensibility of the dilated ascending aorta. Journal of Thoracic and Cardiovascular Surgery 2003; 126: 842-850

Goldstein, JA, Beardslee, MA, Xu, H, Sundt, TM and Lasala, J. Infective endocarditis on a CardioSEAL Device closing a patent formen ovale. Catheterization and and Cardiovascular Interventions. 2002; 55: 217-220

Sundt, TM, Moon, MR, and Xu, H. Reoperation for dilatation of the pulmonary autograft after Ross procedure. Journal of Thoracic and Cardiovascular Surgery 2001; 122: 1249-1252

Li, H, Guo, W, Xu, H, and Nerbonne, JM. Functional expression of a GFP-tagged Kv1.5 a subunit in mouse ventricle. American Journal of Physiology-Heart 2001, 281: H955-967.

Xu, H, Barry, MD, Li, H, Brune S, Guo, W and Nerbonne, JM. Attenuation of the slow component of delay rectification, action potential prolongation, and triggered activity in mice expressing a dominant-negative Kv2 a subunit. Circulation Research 1999; 85:623-633.

Xu, H, Guo, W and Nerbonne, JM. Four kinetically distinct depolarization-activated K+ currents in adult mouse ventricular myocytes. Journal of General Physiology 1999; 113:661-677

Xu, H, Li, H and Nerbonne, JM. Elimination of the transient outward current and action potential prolongation in mouse atrial myocytes expressing a dominant negative Kv4 a subunit. Journal of Physiology 1999;519:11-21.

Guo, W, Xu, H, London, B and Nerbonne JM. Molecular basis of transient outward K+current diversity in mouse ventricular myocytes. Journal of Physiology 1999; 521:587-599.

Barry, DM, Xu, H, Schuessler, RB and Nerbonne, JM. Functional knockout of the cardiac transient outward K+ current in mice expressing a dominant negative voltage-gated K+ channel (Kv4) a subunit. Circulation Research 1998; 83:560-567.

Xu, H, Dixon, JE, Barry, DM, Trimmer, JS, McKinnon, D, Merlie, JP and Nerbonne, JM. Developmental analysis reveals mismatch in the expression of K+ channel a subunits and voltage-gated K+ channel currents in rat ventricular myocytes. Journal of General Physiology 1996; 40:444-478.

 

Helpful Links

• Pathology Department Faculty List
• Areas of Excellence - Anatomic Pathology
• Areas of Excellence - Clinical Pathology
• Pathology Ph.D. Program Faculty

Pathology & Laboratory Medicine Sites

Pathology and Laboratory Medicine URMC Clinical Laboratories URMC Central Laboratory Research and Academics Residency Program Graduate Studies