Qunna Li

Emory Hospitals, Atlanta, Georgia, United States

Are you Qunna Li?

Claim your profile

Publications (16)103.48 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Rationale: Low circulating progenitor cell (PC) numbers and activity may reflect impaired intrinsic regenerative/reparative potential, but it remains uncertain whether this translates into a worse prognosis. Objective: To investigate whether low numbers of PCs associate with a greater risk of mortality in a population at high cardiovascular risk. Methods and Results: Patients undergoing coronary angiography were recruited into two cohorts (1, n=502 and 2, n=403) over separate time periods. PCs were enumerated by flow cytometry as CD(45med+) blood mononuclear cells expressing CD34, with additional quantification of subsets co-expressing CD133, VEGFR2 and CXCR4. Coefficient of variation for CD34 cells was 2.9% and 4.8%, 21.6% and 6.5% for the respective subsets. Each cohort was followed for a mean of 2.7 and 1.2 years, respectively, for the primary endpoint of all-cause death. There was an inverse association between CD34+ and CD34+/CD133+ cell counts and risk of death in Cohort 1 (β=-0.92, p=0.043 and β=-1.64, p=0.019, respectively) that was confirmed in Cohort 2 (β=-1.25, p=0.020 and β=-1.81, p=0.015, respectively). Covariate adjusted HRs in the pooled cohort (n=905) were 3.54 (1.67-7.50) and 2.46 (1.18-5.13), respectively. CD34+/CD133+ cell counts improved risk prediction metrics beyond standard risk factors. Conclusions: Reduced circulating PC counts, identified primarily as CD34+ mononuclear cells or its subset expressing CD133 are associated with risk of death in individuals with coronary artery disease, suggesting that impaired endogenous regenerative capacity is associated with increased mortality. These findings have implications for biological understanding, risk prediction and cell selection for cell based therapies.
    Circulation Research 10/2014; 116(2). DOI:10.1161/CIRCRESAHA.116.304187 · 11.09 Impact Factor
  • International Journal of Cardiology 08/2014; 176(3). DOI:10.1016/j.ijcard.2014.07.282 · 6.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Progenitor cells (PCs) are mobilized in response to vascular injury to effect regeneration and repair. Recruitment of PCs requires intact nitric oxide (NO) synthesis by endothelial cells, and their number and activity correlate with cardiovascular disease risk burden and future outcomes. Whereas cardiovascular vulnerability exhibits a robust circadian rhythm, the 24-hour variation of PCs and their inter-relation with vascular function remain unknown. We investigated the circadian variation of PCs and vascular function with the hypothesis that this will parallel the pattern observed for cardiovascular events (CVEs). In 15 healthy subjects (9 men, 37±16 years), circulating PCs and vascular function were measured at 8 am, noon, 4 pm, 8 pm, midnight, 4 am (only PCs counts), and 8 am the following day. Circulating PCs were enumerated as mononuclear cells (MNCs; CD45(med)) that express CD34 as well as CD133, and their activity was assessed as the number of colonies formed by culturing MNCs. Vascular function was evaluated by measurement of endothelium-dependent, flow-mediated vasodilation (FMD) of the brachial artery and tonometry-derived indices of arterial stiffness. Higher CD34(+) and CD34(+)/CD133(+) cell counts were observed at 8 pm than any other time of the day (P-ANOVA=0.038 and <0.001; respectively) and were lowest at 8 am. PC colony formation was highest at midnight (P-ANOVA=0.045) and lowest in the morning hours. FMD was highest at midnight and lowest at 8 am and 8 pm, and systemic arterial stiffness was greatest at 8 am and lowest at 4 pm and midnight (P-ANOVA=0.03 and 0.01; respectively). A robust circadian variation in PC counts and vascular function occurs in healthy humans and both exhibit an unfavorable profile in the morning hours that parallels the preponderance of CVEs at these times. Whether these changes are precipitated by awakening and time-dependent physical activity or governed by the endogenous circadian clock needs to be further investigated.
    Journal of the American Heart Association 04/2014; 3(3). DOI:10.1161/JAHA.114.000845 · 2.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Background | Methods | Results | Conclusions Circulating progenitor cells (PCs) are mobilized in response to myocardial injury and reflect reparative/regenerative potential. We hypothesized that the degree of PC mobilization differs between different acute coronary syndrome (ACS) presentations. Methods Background | Methods | Results | Conclusions We recruited 90 ACS patients (mean age 65±15 years). Nine patients with STEMI, 69 with NSTEMI and 12 with unstable angina were compared to 180 age- and gender-matched subjects with stable coronary artery disease (CAD). Blood samples were obtained for enumeration of PCs as CD45 dim mononuclear cells by flow cytometry with cells expressing CD34 and CD133 epitopes representing hematopoietic PCs and those expressing vascular endothelial growth factor receptor (VEGF2R) representing endothelial-enriched PCs. Mann-Whitney nonparametric test was used to compare differences in PCs between groups. Results Background | Methods | Results | Conclusions Endothelial-enriched PC levels were higher in patients with STEMI compared to other groups (Table 1) and correlated with peak troponin levels in ACS (CD34+/VEGF2R+: r=0.28, p=0.012; CD34+/CXCR4+/VEGF2R+: r=0.29, p=0.009). These findings persisted after analysis of covariance to account for age, gender, diabetes, smoking status, and statin use.
    J Am Coll Cardiol. 2014;63(12_S):. doi:10.1016/S0735-1097(14)60069-3; 04/2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: IMPORTANCE Many patients with peripheral artery disease (PAD) have walking impairment despite therapy. Experimental studies in animals demonstrate improved perfusion in ischemic hind limb after mobilization of bone marrow progenitor cells (PCs), but whether this is effective in patients with PAD is unknown. OBJECTIVE To investigate whether therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) improves exercise capacity in patients with intermittent claudication. DESIGN, SETTING, AND PARTICIPANTS In a phase 2 double-blind, placebo-controlled study, 159 patients (median [SD] age, 64 [8] years; 87% male, 37% with diabetes) with intermittent claudication were enrolled at medical centers affiliated with Emory University in Atlanta, Georgia, between January 2010 and July 2012. INTERVENTIONS Participants were randomized (1:1) to received 4 weeks of subcutaneous injections of GM-CSF (leukine), 500 μg/day 3 times a week, or placebo. Both groups were encouraged to walk to claudication daily. MAIN OUTCOMES AND MEASURES The primary outcome was peak treadmill walking time (PWT) at 3 months. Secondary outcomes were PWT at 6 months and changes in circulating PC levels, ankle brachial index (ABI), and walking impairment questionnaire (WIQ) and 36-item Short-Form Health Survey (SF-36) scores. RESULTS Of the 159 patients randomized, 80 were assigned to the GM-CSF group. The mean (SD) PWT at 3 months increased in the GM-CSF group from 296 (151) seconds to 405 (248) seconds (mean change, 109 seconds [95% CI, 67 to 151]) and in the placebo group from 308 (161) seconds to 376 (182) seconds (change of 56 seconds [95% CI, 14 to 98]), but this difference was not significant (mean difference in change in PWT, 53 seconds [95% CI, -6 to 112], P = .08). At 3 months, compared with placebo, GM-CSF improved the physical functioning subscore of the SF-36 questionnaire by 11.4 (95% CI, 6.7 to 16.1) vs 4.8 (95% CI, -0.1 to 9.6), with a mean difference in change for GM-CSF vs placebo of 7.5 (95% CI, 1.0 to 14.0; P = .03). Similarly, the distance score of the WIQ improved by 12.5 (95% CI, 6.4 to 18.7) vs 4.8 (95% CI, -0.2 to 9.8) with GM-CSF compared with placebo (mean difference in change, 7.9 [95% CI, 0.2 to 15.7], P = .047). There were no significant differences in the ABI, WIQ distance and speed scores, claudication onset time, or mental or physical component scores of the SF-36 between the groups. CONCLUSIONS AND RELEVANCE Therapy with GM-CSF 3 times a week did not improve treadmill walking performance at the 3-month follow-up. The improvements in some secondary outcomes with GM-CSF suggest that it may warrant further study in patients with claudication. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01041417.
    JAMA The Journal of the American Medical Association 11/2013; 310(24). DOI:10.1001/jama.2013.282540 · 30.39 Impact Factor
  • Journal of the American College of Cardiology 03/2013; DOI:10.1016/S0735-1097(13)61143-2 · 15.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The proper level of estrogen-ER signaling is important for the maintenance of epithelial homeostasis in the breast. In a previous study, we demonstrated that ATBF1, which has been suggested as a tumor suppressor in breast cancer, inhibited estrogen-mediated cell proliferation by selectively competing with AIB1 for binding to ER. However, the expression of ATBF1 mRNA was shown to positively correlate with ER in breast cancer specimens. We therefore examined whether estrogen regulates ATBF1. We demonstrated that estrogen upregulated the transcription of ATBF1, which was mediated by the direct binding of ER onto the ATBF1 promoter, and that a half estrogen-responsive element in the ATBF1 promoter was essential for the direct binding of ER. Furthermore, we found that estrogen at lower levels increased, but at higher levels decreased the expression of ATBF1 protein, which involved the degradation of ATBF1 protein by the estrogen-responsive proteasome system. ATBF1 protein levels fluctuate with estrogen levels. Although lower levels of estrogen increased ATBF1 protein expression, ATBF1 still inhibited cell proliferation caused by lower levels of estrogen. These findings not only reveal an autoregulatory feedback loop between ATBF1 and estrogen-ER signaling, but also suggest that ATBF1 plays a role in both the maintenance of breast epithelial homeostasis and breast tumorigenesis caused by elevated estrogen levels.
    Journal of Biological Chemistry 03/2011; · 4.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The proper level of estrogen-estrogen receptor (ER) signaling is important for the maintenance of epithelial homeostasis in the breast. In a previous study we demonstrated that ATBF1, which has been suggested as a tumor suppressor in breast cancer, inhibited estrogen-mediated cell proliferation by selectively competing with AIB1 for binding to the ER. However, the expression of ATBF1 mRNA was shown to positively correlate with ER in breast cancer specimens. We, therefore, examined whether estrogen regulates ATBF1. We demonstrated that estrogen up-regulated the transcription of ATBF1, which was mediated by the direct binding of the ER onto the ATBF1 promoter, and that a half-estrogen-responsive element in the ATBF1 promoter was essential for ER direct binding. Furthermore, we found that estrogen at lower levels increased, but at higher levels decreased the expression of ATBF1 protein, which involved the degradation of ATBF1 protein by the estrogen-responsive proteasome system. ATBF1 protein levels fluctuate with estrogen levels. Although lower levels of estrogen increased ATBF1 protein expression, ATBF1 still inhibited cell proliferation caused by lower levels of estrogen. These findings not only reveal an autoregulatory feedback loop between ATBF1 and estrogen-ER signaling but also suggest that ATBF1 plays a role in both the maintenance of breast epithelial homeostasis and breast tumorigenesis caused by elevated estrogen levels.
    Journal of Biological Chemistry 03/2011; 286(16):13879-90. DOI:10.1074/jbc.M110.187849 · 4.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Loss of the q22 band of chromosome 16 is a frequent genetic event in breast cancer, and the candidate tumor suppressor gene, ATBF1, has been implicated in breast cancer by genomic deletion, transcriptional down-regulation, and association with better prognostic parameters. In addition, estrogen receptor (ER)-positive breast cancer expresses a higher level of ATBF1, suggesting a role of ATBF1 in ER-positive breast cancer. In this study, we examined whether and how ATBF1 affects the ER function in breast cancer cells. We found that ATBF1 inhibited ER-mediated gene transcription, cell growth, and proliferation in ER-positive breast cancer cells. In vitro and in vivo immunoprecipitation experiments revealed that ATBF1 interacted physically with the ER and that multiple domains in both ATBF1 and ER proteins mediated the interaction. Furthermore, we demonstrated that ATBF1 inhibited ER function by selectively competing with the steroid receptor coactivator AIB1 but not GRIP1 or SRC1 for binding to the ER. These findings not only support the concept that ATBF1 plays a tumor-suppressive role in breast cancer, they also provide a mechanism for how ATBF1 functions as a tumor suppressor in breast cancer.
    Journal of Biological Chemistry 10/2010; 285(43):32801-9. DOI:10.1074/jbc.M110.128330 · 4.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Kruppel-like factor 5 (KLF5) is implicated in human breast cancer by frequent genomic deletion and expressional deregulation, but the molecular mechanisms by which KLF5 affects breast tumorigenesis are still unknown. This study was conducted to examine whether and how KLF5 affects the function of estrogen receptor (ER) in breast cancer cells. Using different cell lines, we found that restored expression of KLF5 inhibited estrogen-promoted cell proliferation in ER-positive MCF-7 and T-47D cell lines but had no effect on ER-negative SK-BR-3 cells. Transcriptional activity of ER was also suppressed by KLF5, as detected by using estrogen-stimulated ER responsive element-mediated reporter assay and expression analysis of ER target genes including c-MYC and Cathepsin D (CSTD). Chromatin immunoprecipitation assays showed that KLF5 inhibited ERalpha binding to the promoter of c-myc and CSTD. Furthermore, estrogen induced an interaction between KLF5 and ERalpha. These results suggest that KLF5 inhibits the function of ERalpha in gene regulation and cell proliferation through protein interaction that interrupts the binding of ERalpha to target gene promoters to prevent target gene induction.
    International Journal of Cancer 01/2010; 126(1):81-9. DOI:10.1002/ijc.24696 · 5.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Deletion of chromosome 6q is frequent in breast cancer, and the deletion often involves a region in 6q14-q16. At present, however, the underlying tumor suppressor gene has not been established. Based on a recent study identifying snoRNA U50 as a candidate for the 6q14-16 tumor suppressor gene in prostate cancer, we investigated whether U50 is also involved in breast cancer. PCR-based approaches showed that U50 underwent frequent genomic deletion and transcriptional downregulation in cell lines derived from breast cancer. Mutation screening identified the same 2-bp deletion of U50 as in prostate cancer in both cell lines and primary tumors from breast cancer, and the deletion was both somatic and in germline. Genotyping of a cohort of breast cancer cases and controls for the mutation demonstrated that, while homozygous genotype of the mutation was rare, its heterozygous genotype occurred more frequently in women with breast cancer. Functionally, re-expression of U50 resulted in the inhibition of colony formation in breast cancer cell lines. These results suggest that noncoding snoRNA U50 plays a role in the development and/or progression of breast cancer.
    Journal of Genetics and Genomics 09/2009; 36(8):447-54. DOI:10.1016/S1673-8527(08)60134-4 · 2.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The proto-oncogene MYC plays a critical role in cell proliferation and tumorigenesis, and its down-regulation by transforming growth factor beta (TGFbeta) signaling is necessary for TGFbeta to inhibit cell proliferation. KLF5, on the other hand, is a pro-proliferative basic transcription factor that reverses function to become an anti-proliferative TGFbeta cofactor upon TGFbeta stimulation in epithelial homeostasis. In this study we investigated whether KLF5 directly regulates MYC transcription in epithelial cells in the context of TGFbeta. Knockdown of KLF5 significantly reduced MYC expression in the HaCaT epidermal epithelial cells. When TGFbeta was applied, however, whereas MYC expression was significantly inhibited, knockdown of KLF5 increased MYC expression. Furthermore, re-expression of KLF5 restored the inhibitory effect of TGFbeta on MYC expression in two cancer cell lines. Chromatin immunoprecipitation and oligo pulldown experiments demonstrated that whereas binding of KLF5 to both KLF5 binding element (KBE) and TGFbeta inhibitory element (TIE) DNA elements was necessary for MYC transcription, binding to KBE was decreased by TGFbeta, and binding to TIE was increased by TGFbeta. These results suggest that KLF5 is not only essential for MYC transcription in proliferating epithelial cells but also mediates the inhibitory effect of TGFbeta on MYC transcription. Furthermore, different binding sites mediate different effects of KLF5 in the context of TGFbeta.
    Journal of Biological Chemistry 09/2009; 284(41):28243-52. DOI:10.1074/jbc.M109.036160 · 4.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: During epithelial homeostasis, stem cells divide to produce progenitor cells, which not only proliferate to generate the cell mass but also respond to cellular signaling to transition from a proliferative state to a differentiation state. Such a transition involves functional alterations of transcriptional factors, yet the underlying molecular mechanisms are poorly understood. Recent studies have implicated Kruppel-like factors (KLFs) including KLF5 in the renewal and maintenance of stem/progenitor cells. Here we demonstrate that the pro-proliferative factor KLF5 becomes anti-proliferative upon TGFbeta-mediated acetylation in an in vitro model of epithelial homeostasis. In the HaCaT epidermal cell line treated with or without TGFbeta, we found that KLF5 was not only essential for cell proliferation, it was also indispensable for TGFbeta-induced anti-proliferation in these cells. KLF5 inhibited the expression of p15 (CDKN2B), a cell cycle inhibitor, without TGFbeta, but became a coactivator in TGFbeta-induced p15 expression in the same cells. Mechanistically, TGFbeta recruited acetylase p300 to acetylate KLF5, and acetylation in turn altered the binding of KLF5 to p15 promoter, resulting in the reversal of KLF5 function. These studies not only demonstrate that a basic transcription factor can be both pro-proliferation and anti-proliferation in epithelial homeostasis, they also present a unique mechanism for how transcriptional regulation changes during the transition from proliferation to inhibition of proliferation. Furthermore, they establish KLF5 as an essential cofactor for TGFbeta signaling.
    Journal of Biological Chemistry 03/2009; 284(10):6071-8. DOI:10.1074/jbc.M806270200 · 4.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Deletion of chromosome 6q14-q22 is common in multiple human cancers including prostate cancer, and chromosome 6 transferred into cancer cells induces senescence and reduces cell growth, tumorigenicity and metastasis, indicating the existence of one or more tumor-suppressor genes in 6q. To identify the 6q tumor-suppressor gene, we first narrowed the common region of deletion to a 2.5 Mb interval at 6q14-15. Of the 11 genes located in this minimal deletion region and expressed in normal prostates, only snoRNA U50 was mutated, demonstrated transcriptional downregulation and inhibited colony formation in prostate cancer cells. The mutation, a homozygous 2 bp (TT) deletion, was found in two of 30 prostate cancer cell lines/xenografts and nine of 89 localized prostate cancers (eleven of 119 or 9% cancers). Two of 89 (2%) patients with prostate cancer also showed the same mutation in their germline DNA, but none of 104 cancer-free control men did. The homozygous deletion abolished U50 function in a colony formation assay. Analysis of 1371 prostate cancer cases and 1371 matched control men from a case-control study nested in a prospective cohort showed that, although a germline heterozygous genotype of the deletion was detected in both patients and controls at similar frequencies, the homozygosity of the deletion was significantly associated with clinically significant prostate cancer (odds ratio 2.9; 95% confidence interval 1.17-7.21). These findings establish snoRNA U50 as a reasonable candidate for the 6q tumor-suppressor gene in prostate cancer and likely in other types of cancers.
    Human Molecular Genetics 05/2008; 17(7):1031-42. DOI:10.1093/hmg/ddm375 · 6.68 Impact Factor

Publication Stats

207 Citations
103.48 Total Impact Points

Institutions

  • 2014
    • Emory Hospitals
      Atlanta, Georgia, United States
  • 2008–2014
    • Emory University
      • • Department of Biostatistics and Bioinformatics
      • • Department of Hematology and Medical Oncology
      Atlanta, Georgia, United States