Yun Gong

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (102)454.17 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: To evaluate the efficacy and the limitation of fine-needle aspiration (FNA) biopsy in thyroid bed lesions, a retrospective review was performed of the medical records of thyroid cancer patients who underwent ultrasound-guided FNA biopsy of the thyroid bed at The University of Texas MD Anderson Cancer Center over a 5-year period. METHODS: Data were reviewed on 220 FNA biopsies taken from thyroid bed lesions in 195 patients who had undergone thyroidectomy for thyroid carcinoma. Thyroid bed FNA results were compared with clinical follow-up, including neck dissection results. RESULTS: Recurrent carcinoma was diagnosed by FNA biopsy in 139 of 220 (63%) cases. Neck dissections were performed for 112 sites identified by FNA biopsies, and recurrent carcinoma was confirmed in 110 sites. The concordance between positive and/or suspicious FNA diagnosis and positive neck dissection results was 98% (118 of 120 cases). A false-positive FNA occurred in one patient with follicular thyroid carcinoma. The other discrepancy was attributed to failure to remove the lesion by neck dissection. The diagnostic accuracy of thyroid bed FNA was 100% in papillary and medullary thyroid carcinoma and 93% in follicular thyroid carcinoma. Suspicious and rare false-negative FNA results were attributed to low cellularity and lack of characteristic cytomorphologic features of thyroid carcinoma. CONCLUSIONS: Ultrasound-guided thyroid bed FNA biopsy is accurate and efficient in triaging patients who require post-thyroidectomy follow-up for recurrent thyroid carcinoma. Caution should be taken in the interpretation of FNA specimens that have low cellularity and lack characteristic cytologic features of thyroid carcinoma. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society.
    Cancer Cytopathology 02/2013; 121(2). DOI:10.1002/cncy.21202 · 3.81 Impact Factor
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    ABSTRACT: The development of mature B cells from hematopoietic stem cells is a strictly orchestrated process involving multiple regulatory genes. The transcription factor Sox4 is required for this process, but its role has not been systematically studied, and the underlying mechanisms remain unknown. To determine when and how Sox4 functions in the stepwise process of B cell development, we used mice harboring conditional null alleles for Sox4 and a Cre transgene. Sox4 deletion in hematopoietic stem cells almost entirely eliminated pro-B cells in both fetal livers and adult bone marrow, resulting in a severe deficiency in later stage B cells, including circulating mature B cells. Sox4-deficient pro-B cells, particularly those expressing the stem cell factor receptor c-Kit, readily underwent apoptosis, and even more so when c-Kit activity was inhibited by imatinib. C-Kit-expressing pro-B cells showed decreased activation of the c-Kit downstream protein Src upon Sox4 deletion. Likewise, the level of the anti-apoptotic Bcl2 protein was decreased in residual pro-B cells, and its restoration using a Bcl2 transgene allowed not only partial rescue of pro-B cell survival but also B cell maturation in the absence of Sox4. Our findings indicate that Sox4 is required for the survival of pro-B cells and may functionally interact with c-Kit and Bcl2.
    The Journal of Immunology 01/2013; 190(5). DOI:10.4049/jimmunol.1202736 · 5.36 Impact Factor
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    ABSTRACT: Leukemia cells are protected by various components of its microenvironment, including marrow stromal cells (MSCs). To understand the molecular mechanisms underlying this protection, we cultured acute lymphoblastic leukemia (ALL) cells with MSCs and studied the effect of the latter on the molecular profiling of ALL cells at the mRNA and protein levels. Our results indicated that activated Wnt signaling in ALL cells is involved in MSC-mediated drug resistance. Blocking the Wnt pathway sensitized the leukemia cells to chemotherapy and improved overall survival in a mouse model. Targeting the Wnt pathway may be an innovative approach to the treatment of ALL.
    Cancer letters 01/2013; DOI:10.1016/j.canlet.2012.11.056 · 5.02 Impact Factor
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    ABSTRACT: Background Inflammatory breast cancer (IBC) is a rare but aggressive type of breast carcinoma. Despite multimodality approaches, the clinical outcome of IBC patients remains poor. Tumors arising from cancer stem cells (CSCs) are associated with drug resistance, tumor recurrence and poor prognosis. We aimed to evaluate expression of aldehyde dehydrogenase 1 (ALDH1), a putative stem cell marker, in IBC tumors. Methods Tissue microarrays of 74 surgically resected IBC tumors were immunohistochemically stained for ALDH1. The results were correlated with clinicopathologic parameters, survival data, and compared with findings published in the literature. Results The median follow-up time of the cohort was 42.1 months, and the 5-year overall survival (OS) rate was 46%. Twenty-four tumors (32%) were positive for ALDH1 staining. However, ALDH1 expression was not significantly associated with clinicopathologic variables, including lymph node status, tumor grade, and ER, PR, and HER2 status. Log-rank testing revealed that ALDH1 expression was not significantly associated with the OS rate although there was a trend toward an association with lower OS rate (P = 0.07). The findings were consistent with some of the published data, but substantial inconsistency among reports was noted. Conclusions Our IBC cohort did not show significant correlation between ALDH1 expression and prognosis or other clinicopathologic variables. Although sample size and selection factors may be contributory factors, inconsistent results reported in the literature raise concern regarding the reliability of immunohistochemically identified ALDH1 as a sole marker of breast CSCs. Further study is required to elucidate the significance of CSCs in IBC biology.
    Clinical Breast Cancer 01/2013; 14(3). DOI:10.1016/j.clbc.2013.12.006 · 2.63 Impact Factor
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    ABSTRACT: OBJECTIVES: Metastatic lesions to the pancreas pose diagnostic challenges with regards to their differentiation from primary pancreatic cancer. Data on the yield of endoscopic ultrasonography (EUS)-guided fine-needle aspiration in detection of these lesions are limited. METHODS: This is a retrospective review of 23 patients referred to a tertiary referral center for further evaluation of suspected pancreatic metastases. Main outcome measures were diagnostic yield of endoscopic ultrasonography-guided fine-needle aspiration in evaluation of metastatic lesions to the pancreas. RESULTS: Of 644 patients, 23 (3.6%) undergoing EUS of the pancreas were diagnosed to have metastatic disease to the pancreas based on clinical, radiological, and cytological results. Mean (SD) age was 64.3 (11.7) years. Of the 23 patients, 18 (78.3%) were asymptomatic. Mean (SD) size of lesion on EUS was 39.1 (19.9) mm. A diagnosis of malignant lesion was made in 21 of 23 cases, with a diagnostic accuracy of 91.3%. CONCLUSIONS: Metastatic lesions to the pancreas present as incidental, solitary mass lesions on staging or surveillance imaging. Endoscopic ultrasonography-guided fine-needle aspiration is an important tool in the characterization and further differentiation of metastatic lesions to the pancreas from primary pancreatic cancer.
    Pancreas 12/2012; DOI:10.1097/MPA.0b013e31826c276d · 3.01 Impact Factor
  • 11/2012; 1(1):S71. DOI:10.1016/j.jasc.2012.08.156
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    ABSTRACT: Patients with ovarian serous tumors of low malignant potential (OSLMP) who have peritoneal implants, especially invasive implants, are at an increased risk of developing tumor recurrence. To the best of the authors' knowledge, the ability of peritoneal washing (PW) cytology to detect the presence and type of peritoneal implants has not been adequately investigated, and its prognostic significance is unknown. Records and PW specimens of 101 patients diagnosed with and treated for OSLMP between 1996 and 2010 at The University of Texas MD Anderson Cancer Center were retrospectively reviewed. Patients' staging biopsy findings were compared with the results of the authors' review of the PWs. Follow-up data were also analyzed. Of the 96 patients for whom staging biopsy results were available, 26 (27%) had peritoneal implants (17 noninvasive and 9 invasive), 19 (20%) had endosalpingiosis, and 51 (53%) had negative findings. The PW specimens of 18 of the 26 patients (69%) with peritoneal implants were positive for serous neoplasm, and a correlation was found between cytologic and histologic findings (P < .0001). The sensitivity, specificity, positive predictive value, and negative predictive value were 69%, 84%, 62%, and 88%, respectively. Four of 101 patients had disease recurrence; 3 of these patients had invasive implants and 1 patient had noninvasive implants. None of the patients who had negative staging biopsy findings or endosalpingiosis but did have PW specimens that were positive for serous neoplasm developed disease recurrence. PW cytology detects the presence of peritoneal implants with moderate accuracy. However, long-term studies are needed to determine whether positive PW cytologic findings are an independent predictor of tumor recurrence.
    Cancer Cytopathology 08/2012; 120(4):238-44. DOI:10.1002/cncy.21219 · 3.81 Impact Factor
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    ABSTRACT: To facilitate accurate detection of estrogen receptor (ER) expression in breast tumors, the American Society of Clinical Oncology/College of American Pathologists recommends that cold ischemia time be kept under 1 h. However, data to address the upper threshold of cold ischemia time are limited. Although it is our routine practice to keep cold ischemia time under 1 h for breast core biopsy specimens, this is difficult for surgical specimens because of the comprehensive intraoperative assessment performed at our institution. In this retrospective study, we compared ER immunohistochemical staining results in paired breast tumor core biopsy specimens and resection specimens with cold ischemia times ranging from 64 to 357 min in 97 patients. The staining category (≥10%, positive; 1-9%, low positive; <1%, negative) between the core biopsy and resection specimens changed for five patients (5%). The weighted Kappa statistic for ER staining category between the two specimen types was 0.86 (95% confidence interval, 0.74-0.99), indicating good concordance. The difference in the percentage of ER staining between core biopsy and resection was not significantly associated with cold ischemia time (P=0.81, Spearman correlation). Although we did not observe significant associations between the difference in ER staining in the two specimen types and cold ischemia time after placing the patients in three groups of 'increase', 'decrease' and 'no change' using a difference of 25% in ER staining percentage as the cutoff, a trend of decreased ER staining with cold ischemia time >2 h was detected. No statistically significant association was found between the change of ER staining and the history of neoadjuvant chemotherapy. Our findings indicate that prolonged cold ischemia time up to 4 h (97% of our cohort) in the practice setting of our institution has minimal clinical impact on ER immunohistochemical expression in breast tumors.Modern Pathology advance online publication, 17 August 2012; doi:10.1038/modpathol.2012.135.
    Modern Pathology 08/2012; DOI:10.1038/modpathol.2012.135 · 6.36 Impact Factor
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    ABSTRACT: Inflammatory breast cancer (IBC) is a highly angiogenic disease; thus, antiangiogenic therapy should result in a clinical response. However, clinical trials have demonstrated only modest responses, and the reasons for these outcomes remain unknown. Therefore, the purpose of this retrospective study was to determine the prognostic value of protein levels of vascular endothelial growth factor (VEGF-A), one of the main targets of antiangiogenic therapy, and its receptors (VEGF-R1 and -R2) in IBC tumor specimens. Specimens from IBC and normal breast tissues were obtained from Algerian patients. Tumor epithelial and stromal staining of VEGF-A, VEGF-R1, and VEGF-R2 was evaluated by immunohistochemical analysis in tumors and normal breast tissues; this expression was correlated with clinicopathological variables and breast cancer-specific survival (BCSS) and disease-free survival (DFS) duration. From a set of 117 IBC samples, we evaluated 103 ductal IBC tissues and 25 normal specimens. Significantly lower epithelial VEGF-A immunostaining was found in IBC tumor cells than in normal breast tissues (P <0.01), cytoplasmic VEGF-R1 and nuclear VEGF-R2 levels were slightly higher, and cytoplasmic VEGF-R2 levels were significantly higher (P = 0.04). Sixty-two percent of IBC tumors had high stromal VEGF-A expression. In univariate analysis, stromal VEGF-A levels predicted BCSS and DFS in IBC patients with estrogen receptor-positive (P <0.01 for both), progesterone receptor-positive (P = 0.04 and P = 0.03), HER2+ (P = 0.04 and P = 0.03), and lymph node involvement (P <0.01 for both). Strikingly, in a multivariate analysis, tumor stromal VEGF-A was identified as an independent predictor of poor BCSS (hazard ratio [HR]: 5.0; 95% CI: 2.0-12.3; P <0.01) and DFS (HR: 4.2; 95% CI: 1.7-10.3; P <0.01). To our knowledge, this is the first study to demonstrate that tumor stromal VEGF-A expression is a valuable prognostic indicator of BCSS and DFS at diagnosis and can therefore be used to stratify IBC patients into low-risk and high-risk groups for death and relapses. High levels of tumor stromal VEGF-A may be useful for identifying IBC patients who will benefit from anti-angiogenic treatment.
    BMC Cancer 07/2012; 12:298. DOI:10.1186/1471-2407-12-298 · 3.32 Impact Factor
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    ABSTRACT: We retrospectively reviewed 25 fine-needle aspiration cases of sclerosing adenosis of the breast in conjunction with histologic features of the paired core-needle biopsy and radiologic findings. The original cytologic diagnoses were benign (n = 19), focally atypical (n = 3), and suspicious for carcinoma (n = 3). The frequent features, although not specific, were low-to-moderate cellularity, bland epithelial cells that focally formed cohesive groups/tubules or occasionally discohesive clusters or individual cells, and fragments of dense fibrous stroma. Some tubules had an angulated configuration. Myoepithelial cells were present in all cases but were scant or absent in small epithelial groups. These cytologic features closely reflected the histologic appearances (ie, compressed and attenuated tubules and sclerotic stroma), but may cause overinterpretation on cytologic smears, especially when angulated tubules, discohesive or individual epithelial cells, scanty myoepithelial cells, and nuclear atypia are noted concurrently. Familiarity with its cytologic features may prevent false-positive diagnosis. Histologic confirmation is recommended for difficult cases.
    American Journal of Clinical Pathology 07/2012; 138(1):96-102. DOI:10.1309/AJCP8MN5GXFZULRD · 3.01 Impact Factor
  • Journal of Clinical Oncology 06/2012; 30(22):e202-6. DOI:10.1200/JCO.2011.40.2230 · 17.88 Impact Factor
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    ABSTRACT: Huo L, Zhang J, Gilcrease M Z, Gong Y, Wu Y, Zhang H, Resetkova E, Hunt K K & Deavers M T (2012) Histopathology Gross cystic disease fluid protein-15 and mammaglobin A expression determined by immunohistochemistry is of limited utility in triple-negative breast cancer Aims:  In addition to oestrogen and progesterone receptors, gross cystic disease fluid protein-15 (GCDFP-15) and mammaglobin A (MAM) are the most common markers used to identify breast origin by immunohistochemistry. GCDFP-15 expression has been reported in approximately 60% of breast carcinomas and MAM expression in approximately 80%. Data on their expression in triple-negative breast cancer (TNBC) are very limited. The aim of this study was to examine the expression of these markers in TNBC to determine their utility in pathological diagnosis. Methods and results:  We studied the immunohistochemical (IHC) expression of GCDFP-15 and MAM in 63 primary and 118 metastatic TNBCs. GCDFP-15 staining was present in 14% of primary and 21% of metastatic TNBCs. MAM staining was present in 25% of primary and 41% of metastatic TNBCs. The frequency of expression of GCDFP-15 and/or MAM was 30% in primary and 43% in metastatic TNBCs, and many positive tumours had only focal staining. Conclusions:  Staining for GCDFP-15 and/or MAM in triple-negative carcinomas helps to confirm breast origin, but most tumours in this subgroup of breast carcinomas lack expression of either marker.
    Histopathology 06/2012; 62(2). DOI:10.1111/j.1365-2559.2012.04344.x · 3.30 Impact Factor
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    ABSTRACT: Diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC) by ultrasound-guided fine-needle aspiration (FNA) is challenging. In this retrospective review, we evaluated triage efficacy (i.e., potential for triggering surgical intervention) in 44 archived FNA biopsies of surgically confirmed FVPTC obtained between December 2006 and December 2008. We compared the original FNA diagnoses with reclassified diagnoses based on 2007 National Cancer Institute (NCI)/Bethesda recommendations, and reviewed FNA cytologic features. Original FNA diagnoses included colloid nodule (7%, 3/44), atypical follicular cells (5%, 2/44), follicular lesion (11%, 5/44), follicular neoplasm (16%, 7/44), suspicious for malignancy/PTC (27%, 12/44), and papillary thyroid carcinoma (34%, 15/44). Reclassified diagnoses included indeterminate (5%, 2/44), colloid nodule (7%, 3/44), atypical cells of undetermined significance [ACUS] (7%, 3/44), Hurthle cell neoplasm (2%, 1/44), follicular neoplasm (7%, 3/44), suspicious for malignancy/PTC (25%, 11/44), and PTC (48%, 21/44). Triage efficacy was 77% (34/44) for original diagnoses versus 82% (36/44) for reclassified FNA diagnoses. We frequently observed cytologic features of PTC, such as nuclear grooves and fine chromatin; conversely, intranuclear inclusions, though present in 77% cases, were scant. Our review findings suggest that lack of characteristic cytologic features of PTC,coexistence with other thyroid lesions, and small tumor size arethe major obstacles to FNA diagnosis of FVPTC. Reclassification of thyroid FNA diagnoses does not significantly improve triage efficacy. Furthermore, FNA diagnoses of follicular neoplasm and suspicious for malignancy are valuable in patients with FVPTC because they trigger triage toward surgical intervention.
    Diagnostic Cytopathology 05/2012; 40 Suppl 1(S1):E69-73. DOI:10.1002/dc.21718 · 1.52 Impact Factor
  • Gastrointestinal Endoscopy 04/2012; 75(4):AB266. DOI:10.1016/j.gie.2012.04.278 · 4.90 Impact Factor
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    ABSTRACT: Invasive ductal and lobular breast carcinomas often have different preferred metastasis sites and distinct histomorphologic characteristics. Their metastatic cytomorphologic cell features in body cavity fluids are generally readily recognized, but the single-cell/mesothelial-like pattern and its relationship to the primary tumor type have not been well studied, nor whether metastases have a propensity for certain body cavity sites on the basis of the primary tumor type. To further assess the tumor type and single-cell pattern of breast carcinoma metastases in pleural and peritoneal effusions, we retrospectively studied 853 pleural and peritoneal effusions and correlated the findings with the primary tumor type. When necessary, the single- cell/mesothelial-like pattern was documented immunohistochemically. Metastatic breast carcinomas represented 249 (50.8%) of 490 pleural and 51 (14.0%) of 363 peritoneal effusions. Most metastases in pleural and peritoneal effusions were ductal carcinomas (92.4% and 62.7%, respectively). Lobular carcinoma accounted for only 2 (0.8%) of 249 pleural and 11 (21.6%) of 51 peritoneal effusions. The single-cell/mesothelial-like cell pattern was found in all lobular carcinomas but also in 11 (6.0%) of 184 reviewed ductal carcinomas (nine pleural and two peritoneal). Awareness of these findings and the use of immunohistochemical analyses are necessary for accurately diagnosing metastatic breast carcinoma, especially lobular type.
    Diagnostic Cytopathology 04/2012; 40(4):311-5. DOI:10.1002/dc.21563 · 1.52 Impact Factor
  • Pancreas 03/2012; 41(2):327-9. DOI:10.1097/MPA.0b013e3182297885 · 3.01 Impact Factor
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    ABSTRACT: Estrogen receptor-alpha 36 (ER-α36) is a variant of ER-α that has been found to be expressed in conventional ER (ER-α66)-negative breast cancer cell lines and human breast cancer samples. In this study, we found that, using immunohistochemical study, ER-α36 expression was significantly higher in ER-negative tumors than in ER-positive tumors although the expression was not associated with other clinicopathological characteristics. We then constructed an ER-α36-specific microRNA hairpin vector and established stable ER-α36 knockdown cells, and found that the knockdown cells were more sensitive to paclitaxel; the c-Jun N-terminal kinase pathway appeared to be involved in the mechanism. Downregulation of ER-α36 also resulted in decreased migration and invasion. These changes were estrogen independent. Our findings indicated that target ER-α36 may be a strategy for treating ER-negative breast cancers.
    Steroids 02/2012; 77(6):666-73. DOI:10.1016/j.steroids.2012.02.013 · 2.72 Impact Factor
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    ABSTRACT: We evaluated the detection rates of PAX8 and WT1 immunostaining in 68 (45 as cell blocks, 23 as smears) serous effusion specimens that had a cytologic diagnosis of metastatic carcinoma of ovarian origin. Of the cases, 58 (85%) were positive for PAX8, 56 (82%) were positive for WT1, and 64 (94%) were immunoreactive with either or both markers. Detection rates of PAX8 and WT1 were 85% (44/52) and 92% (48/52), respectively, for metastatic serous carcinoma and 100% (5/5) and 20% (1/5), respectively, for metastatic clear cell carcinoma. Detection rates using cell blocks and smears were 91% and 78%, respectively, with PAX8 and 82% and 83%, respectively, with WT1. We concluded that PAX8 and WT1 had comparable overall detection rates in confirming ovarian origin of malignant effusion. The combination of both markers substantially improved the detection rate. Cell blocks and smears can be used for staining, but a cell block is preferred for PAX8 staining.
    American Journal of Clinical Pathology 02/2012; 137(2):304-9. DOI:10.1309/AJCPU0FION3RKKFO · 3.01 Impact Factor
  • Yun Gong
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    ABSTRACT: Information on hormone receptor and human epidermal growth factor receptor 2 (HER2) is important for making optimal therapeutic decisions for breast cancer patients. Discordance in these biomarkers between primary breast carcinomas and corresponding metastases is well documented and may lead to changes in management option. The underlying mechanisms of biomarker discordance are complicated and multifactorial. Whereas biologic evolution, intratumoral heterogeneity, and subclonal selection may account for discordance, variations in sampling, processing, staining procedure and interpretation are the important contributory yet controllable factors. This article reviews the effects of different factors on the biomarker discordance, the clinical significance and the importance of standardizing methodology and interpretation criteria.
    Cancer biomarkers: section A of Disease markers 01/2012; 12(6):207-18. DOI:10.3233/CBM-130316 · 1.19 Impact Factor
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    ABSTRACT: Enhancer of zeste homolog 2 (EZH2), a member of polycomb group proteins, is involved in the regulation of cell cycle progression and has been implicated in various human malignancies, including breast cancer, and also has been associated with aggressive tumor behavior. However, the clinical significance of EZH2 expression in inflammatory breast cancer (IBC), a rare but aggressive type of breast carcinoma, has not been explored. In this retrospective study, the authors examined EZH2 expression in IBC tumors and evaluated the relation between EZH2 expression and patient survival. Tissue microarrays of 88 surgically resected IBC tumors were stained immunohistochemically for EZH2, and the authors evaluated the association of EZH2 expression status with clinicopathologic factors and clinical outcome. The median follow-up for the entire cohort was 45.7 months, and the 5-year overall survival (OS) rate was 45%. EZH2 was expressed frequently in IBC tumors (75.7%) and was associated significantly with unfavorable prognostic factors, such as higher tumor grade, negative estrogen receptor status, and triple-negative status (ie, negative for the estrogen, progesterone, and human epidermal growth factor 2 receptors). Univariate survival analysis indicated that patients who had EZH2-positive IBC had a significantly lower 5-year OS rate than patients who had EZH2-negative IBC (P = .01). In multivariate analysis, only positive EZH2 status remained an independent predictor of worse OS. EZH2 was expressed frequently in IBC tumors. The current results indicated that EZH2 expression status may be used to identify a subset of patients with IBC who have a relatively worse prognosis. Targeting EZH2 also may provide a novel strategy for improving the clinical outcome of patients with IBC.
    Cancer 12/2011; 117(24):5476-84. DOI:10.1002/cncr.26179 · 4.90 Impact Factor

Publication Stats

2k Citations
454.17 Total Impact Points

Institutions

  • 2003–2015
    • University of Texas MD Anderson Cancer Center
      • Department of Pathology
      Houston, Texas, United States
    • University of Illinois at Chicago
      Chicago, Illinois, United States
  • 2011
    • University of Texas Health Science Center at Houston
      Houston, Texas, United States
  • 2009
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 2005–2008
    • University of Houston
      Houston, Texas, United States
  • 2002
    • Children's Memorial Hospital
      Chicago, Illinois, United States