Hannah A Valantine

National Institutes of Health, 베서스다, Maryland, United States

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Publications (219)1619.16 Total impact

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    ABSTRACT: Purpose: One challenge academic health centers face is to advance female faculty to leadership positions and retain them there in numbers equal to men, especially given the equal representation of women and men among graduates of medicine and biological sciences over the last 10 years. The purpose of this study is to investigate the explicit and implicit biases favoring men as leaders, among both men and women faculty, and to assess whether these attitudes change following an educational intervention. Method: The authors used a standardized, 20-minute educational intervention to educate faculty about implicit biases and strategies for overcoming them. Next, they assessed the effect of this intervention. From March 2012 through April 2013, 281 faculty members participated in the intervention across 13 of 18 clinical departments. Results: The study assessed faculty members' perceptions of bias as well as their explicit and implicit attitudes toward gender and leadership. Results indicated that the intervention significantly changed all faculty members' perceptions of bias (P < .05 across all eight measures). Although, as expected, explicit biases did not change following the intervention, the intervention did have a small but significant positive effect on the implicit biases surrounding women and leadership of all participants regardless of age or gender (P = .008). Conclusions: These results suggest that providing education on bias and strategies for reducing it can serve as an important step toward reducing gender bias in academic medicine and, ultimately, promoting institutional change, specifically the promoting of women to higher ranks.
    No preview · Article · Jan 2016 · Academic Medicine
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    ABSTRACT: Background: Gender stereotypes in science impede supportive environments for women. Research suggests that women's perceptions of these environments are influenced by stereotype threat (ST): anxiety faced in situations where one may be evaluated using negative stereotypes. This study developed and tested ST metrics for first time use with junior faculty in academic medicine. Methods: Under a 2012 National Institutes of Health Pathfinder Award, Stanford School of Medicine's Office of Diversity and Leadership, working with experienced clinicians, social scientists, and epidemiologists, developed and administered ST measures to a representative group of junior faculty. Results: 174 School of Medicine junior faculty were recruited (62% women, 38% men; 75% assistant professors, 25% instructors; 50% white, 40% Asian, 10% underrepresented minority). Women reported greater susceptibility to ST than did men across all items including ST vulnerability (p < 0.001); rejection sensitivity (p = 0.001); gender identification (p < 0.001); perceptions of relative potential (p = 0.048); and, sense of belonging (p = 0.049). Results of career-related consequences of ST were more nuanced. Compared with men, women reported lower beliefs in advancement (p = 0.021); however, they had similar career interest and identification, felt just as connected to colleagues, and were equally likely to pursue careers outside academia (all p > 0.42). Conclusions: Innovative ST metrics can provide a more complete picture of academic medical center environments. While junior women faculty are susceptible to ST, they may not yet experience all of its consequences in their early careers. As such, ST metrics offer a tool for evaluating institutional initiatives to increase supportive environments for women in academic medicine.
    No preview · Article · Nov 2015 · Journal of Women's Health
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    ABSTRACT: Editors' Summary Background Fifty years ago, little could be done to help a person whose heart, liver, or kidneys had stopped working because of infection, injury, or a chronic disease process. Nowadays, solid organ transplantation gives more than 100,000 people worldwide a new lease on life every year. Many different organs can be successfully moved from one individual (the organ donor), who may be dead or alive, into another individual (the organ recipient). However, organ transplantation remains a complex and risky procedure. The organ recipient may not survive transplantation surgery, and sometimes the transplanted organ fails to work in its new owner. Another major risk for patients who receive an allograft (an organ from another person) is acute rejection. Our immune system protects us from pathogens (disease-causing organisms) by recognizing specific molecules (antigens) on an invader’s surface as foreign and initiating a sequence of events that kills the invader. Unfortunately, the immune system sometimes recognizes organ transplants as foreign and triggers acute transplant rejection. The chances of rejection can be minimized by “matching” the antigens on the donated organ to those on recipient’s organs and by giving the recipient immunosuppressive drugs such as prednisone and tacrolimus. Why Was This Study Done? The primary aim of post-transplantation immunosuppression is to prevent acute rejection, which is associated with the activation of T cells (a type of lymphocyte or white blood cell). But immunosuppressive therapy also affects other immune system cells, including B cells, another type of lymphocyte. B cells make antibodies, molecules that recognize foreign antigens and tag pathogens for destruction by the immune system. It is important, therefore, to get the level of immunosuppression just right for every patient—too little and the transplanted organ will be rejected, too much and the patient will be susceptible to infections. In this proof-of-concept study, the researchers ask whether measurement of the B cell repertoire (the mixture of antibodies produced by a person’s B cells) can be used to assess the overall level of immunosuppression in patients after heart transplantation. When the body is threatened by a pathogen, naïve B cells undergo molecular processes called hypermutation and class-switch recombination. Hypermutation allows the immune system to adapt to new threats by changing the specificity and strength of antibody binding to antigens and involves changes in the “variable” regions of antibodies. Class-switch recombination changes the “isotype” of the antibody produced by a B cell by switching the constant region of the antibody’s “heavy chain.” Thus, determination of the composition of immunoglobulin heavy chain transcripts (nucleotide sequences that are translated into antibodies) in the blood could indicate the level of immunosuppression in an individual. What Did the Researchers Do and Find? The researchers obtained blood samples collected over several months from twelve patients who had had a heart transplant, including six who had experienced a rejection event. Using a previously developed barcode-based immune repertoire sequencing assay, the researchers measured changes over time in the sequence and abundance of immunoglobulin heavy chains in the patients. They found that the fraction of antibody sequences related to activated B cells was inversely related to the level of tacrolimus in the patients’ blood and that antibody repertoire sequencing could detect immune activation during acute rejection events diagnosed by examining small pieces of the donated heart or by looking for donor-derived DNA in the recipients’ blood. Specifically, the immune repertoire sequencing assay diagnosed acute allograft rejection with a sensitivity of 71.4% and a specificity of 82.0%. That is, the assay correctly identified 71.4% of patients who had had a rejection event and 82.0% patients who had not had a rejection event. What Do These Findings Mean? These findings suggest that measurement of the immune repertoire using a high-throughput sequencing assay might provide an accurate and sensitive way to manage immunosuppression in patients who have received an organ or tissue transplant. Importantly, however, these findings provide only proof of concept. Large prospective studies are now needed to confirm the ability of immune repertoire sequencing to predict rejection events and to compare this approach to existing assays for transplant rejection. If validated, immune repertoire sequencing may eventually make it possible to personalize immunosuppressive therapy after transplantation to ensure adequate suppression of the immune system’s response to the allograft while avoiding the many long-term consequences of over-immunosuppression. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001890. The UK National Health Service provides information about heart transplants, including a personal story The British Heart Foundation, a not-for-profit organization, also provides information about heart transplants The US National Heart, Lung, and Blood Institute provides further information about heart transplantation The British Liver Trust, a not-for-profit organization, explains why immunosuppression is needed after organ transplantation and describes some of the possible side effects of immunosuppressive drugs Wikipedia has pages about B cells and about organ transplantation (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) The MedlinePlus Medical Encyclopedia has pages on heart transplantation and on transplant rejection (in English and Spanish); MedlinePlus also provides links to further information about heart transplantation and organ transplantation
    Preview · Article · Oct 2015 · PLoS Medicine
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    Hannah A. Valantine · Francis S. Collins
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    ABSTRACT: The US biomedical research workforce does not currently mirror the nation's population demographically, despite numerous attempts to increase diversity. This imbalance is limiting the promise of our biomedical enterprise for building knowledge and improving the nation's health. Beyond ensuring fairness in scientific workforce representation, recruiting and retaining a diverse set of minds and approaches is vital to harnessing the complete intellectual capital of the nation. The complexity inherent in diversifying the research workforce underscores the need for a rigorous scientific approach, consistent with the ways we address the challenges of science discovery and translation to human health. Herein, we identify four cross-cutting diversity challenges ripe for scientific exploration and opportunity: research evidence for diversity's impact on the quality and outputs of science; evidence-based approaches to recruitment and training; individual and institutional barriers to workforce diversity; and a national strategy for eliminating barriers to career transition, with scientifically based approaches for scaling and dissemination. Evidence-based data for each of these challenges should provide an integrated, stepwise approach to programs that enhance diversity rapidly within the biomedical research workforce.
    Preview · Article · Sep 2015 · Proceedings of the National Academy of Sciences
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    ABSTRACT: The survival rate following lung transplantation is among the lowest of all solid-organ transplants, and current diagnostic tests often fail to distinguish between infection and rejection, the two primary posttransplant clinical complications. We describe a diagnostic assay that simultaneously monitors for rejection and infection in lung transplant recipients by sequencing of cell-free DNA (cfDNA) in plasma. We determined that the levels of donor-derived cfDNA directly correlate with the results of invasive tests of rejection (area under the curve 0.9). We also analyzed the nonhuman cfDNA as a hypothesis-free approach to test for infections. Cytomegalovirus is most frequently assayed clinically, and the levels of CMV-derived sequences in cfDNA are consistent with clinical results. We furthermore show that hypothesis-free monitoring for pathogens using cfDNA reveals undiagnosed cases of infection, and that certain infectious pathogens such as human herpesvirus (HHV) 6, HHV-7, and adenovirus, which are not often tested clinically, occur with high frequency in this cohort.
    No preview · Article · Apr 2015 · The Journal of Heart and Lung Transplantation

  • No preview · Article · Mar 2015 · Journal of the American College of Cardiology
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    ABSTRACT: The basis for increased mortality after heart transplantation in African Americans and other non-Caucasian racial groups is poorly defined. We hypothesized that increased risk of adverse events is driven by biologic factors. To test this hypothesis in the Invasive Monitoring Attenuation through Gene Expression (IMAGE) study, we determined whether the event rate of the primary outcome of acute rejection, graft dysfunction, death, or retransplantation varied by race as a function of calcineurin inhibitor (CNI) levels and gene expression profile (GEP) scores. We determined the event rate of the primary outcome, comparing racial groups, stratified by time after transplant. Logistic regression was used to compute the relative risk across racial groups, and linear modeling was used to measure the dependence of CNI levels and GEP score on race. In 580 patients monitored for a median of 19 months, the incidence of the primary end point was 18.3% in African Americans, 22.2% in other non-Caucasians, and 8.5% in Caucasians (p < 0.001). There were small but significant correlations of race and tacrolimus trough levels to the GEP score. Tacrolimus levels were similar among the races. Of patients receiving tacrolimus, other non-Caucasians had higher GEP scores than the other racial groups. African American recipients demonstrated a unique decrease in expression of the FLT3 gene in response to higher tacrolimus levels. African Americans and other non-Caucasian heart transplant recipients were 2.5-times to 3-times more likely than Caucasians to experience outcome events in the Invasive Monitoring Attenuation through Gene Expression study. The increased risk of adverse outcomes may be partly due to the biology of the alloimmune response, which is less effectively inhibited at similar tacrolimus levels in minority racial groups. Copyright © 2015 International Society for Heart and Lung Transplantation. All rights reserved.
    No preview · Article · Feb 2015 · The Journal of Heart and Lung Transplantation

  • No preview · Article · Sep 2014 · Journal of the American College of Cardiology

  • No preview · Article · Sep 2014 · Journal of the American College of Cardiology
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    ABSTRACT: By applying the strengths of corporate models for effective teamwork, academic scientists can drive transdisciplinary research and accelerate biomedical translation.
    Full-text · Article · Aug 2014 · Science translational medicine
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    ABSTRACT: Monitoring allograft health is an important component of posttransplant therapy. Endomyocardial biopsy is the current gold standard for cardiac allograft monitoring but is an expensive and invasive procedure. Proof of principle of a universal, noninvasive diagnostic method based on high-throughput screening of circulating cell-free donor-derived DNA (cfdDNA) was recently demonstrated in a small retrospective cohort. We present the results of a prospective cohort study (65 patients, 565 samples) that tested the utility of cfdDNA in measuring acute rejection after heart transplantation. Circulating cell-free DNA was purified from plasma and sequenced (mean depth, 1.2 giga-base pairs) to quantify the fraction of cfdDNA. Through a comparison with endomyocardial biopsy results, we demonstrate that cfdDNA enables diagnosis of acute rejection after heart transplantation, with an area under the receiver operating characteristic curve of 0.83 and sensitivity and specificity that are comparable to the intrinsic performance of the biopsy itself. This noninvasive genome transplant dynamics approach is a powerful and informative method for routine monitoring of allograft health without incurring the risk, discomfort, and expense of an invasive biopsy.
    Full-text · Article · Jun 2014 · Science translational medicine
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    ABSTRACT: Purpose To assess whether the proportion of women faculty, especially at the full professor rank, increased from 2004 to 2010 at Stanford University School of Medicine after a multifaceted intervention. Method The authors surveyed gender composition and faculty satisfaction five to seven years after initiating a multifaceted intervention to expand recruitment and development of women faculty. The authors assessed pre/post relative change and rates of increase in women faculty at each rank, and faculty satisfaction; and differences in pre/post change and estimated rate of increase between Stanford and comparator cohorts (nationally and at peer institutions). Results Post intervention, women faculty increased by 74% (234 to 408), with assistant, associate, and full professors increasing by 66% (108 to 179), 87% (74 to 138), and 75% (52 to 91), respectively. Nationally and at peer institutions, women faculty increased by about 30% (30,230 to 39,200 and 4,370 to 5,754, respectively), with lower percentages at each rank compared with Stanford. Estimated difference (95% CI) in annual rate of increase was larger for Stanford versus the national cohort: combined ranks 0.36 (0.17 to 0.56), P = .001; full professor 0.40 (0.18 to 0.62), P = .001; and versus the peer cohort: combined ranks 0.29 (0.07 to 0.51), P = .02; full professor 0.37 (0.14 to 0.60), P = .003. Stanford women faculty satisfaction increased from 48% (2003) to 71% (2008). Conclusions Increased satisfaction and proportion of women faculty, especially full professors, suggest that the intervention may ameliorate the gender gap in academic medicine.
    No preview · Article · Jun 2014 · Academic medicine: journal of the Association of American Medical Colleges
  • M. Deng · A. Kfoury · J. Teuteberg · B. Elashoff · D. Hiller · J. Yee · H. Valantine

    No preview · Article · Apr 2014 · The Journal of Heart and Lung Transplantation
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    Preview · Article · Apr 2014 · Journal of the American College of Cardiology

  • No preview · Article · Apr 2014 · The Journal of Heart and Lung Transplantation
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    ABSTRACT: Gene expression profiling test scores have primarily been used to identify heart transplant recipients who have a low probability of rejection at the time of surveillance testing. We hypothesized that the variability of gene expression profiling test scores within a patient may predict risk of future events of allograft dysfunction or death. Patients from the IMAGE study with rejection surveillance gene expression profiling tests performed at 1- to 6-month intervals were selected for this cohort study. Gene expression profiling score variability was defined as the standard deviation of an individual's cumulative test scores. Gene expression profiling ordinal score (range, 0-39), threshold score (binary value=1 if ordinal score ≥34), and score variability were studied in multivariate Cox regression models to predict future clinical events. Race, age at time of transplantation, and time posttransplantation were significantly associated with future events in the univariate analysis. In the multivariate analyses, gene expression profiling score variability, but not ordinal scores or scores over threshold, was independently associated with future clinical events. The regression coefficient P values were <0.001, 0.46, and 0.773, for gene expression profiling variability, ordinal, and threshold scores, respectively. The hazard ratio for a 1 unit increase in variability was 1.76 (95% CI, 1.4-2.3). The variability of a heart recipient's gene expression profiling test scores over time may provide prognostic utility. This information is independent of the probability of acute cellular rejection at the time of testing that is rendered from a single ordinal gene-expression profiling test score.
    Full-text · Article · Mar 2014 · Transplantation
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    ABSTRACT: To test, whether 10 genes, diagnostic of renal allograft rejection in blood, are able to diagnose and predict cardiac allograft rejection, we analyzed 250 blood samples from heart transplant recipients with and without acute rejection (AR) and with cytomegalovirus (CMV) infection by QPCR. A QPCR-based logistic regression model was built on 5 of these 10 genes (AR threshold composite score>37% = AR) and tested for AR prediction in an independent set of 109 samples, where it correctly diagnosed AR with 89% accuracy, with no misclassifications for AR ISHLT grade 1b. CMV infection did not confound the AR score. The genes correctly diagnosed AR in a blood sample within 6 months prior to biopsy diagnosis with 80% sensitivity and untreated grade 1b AR episodes had persistently elevated scores until 6 months after biopsy diagnosis. The gene score was also correlated with presence or absence of cardiac allograft vasculopathy (CAV) irrespective of rejection grade. In conclusion, there is a common transcriptional axis of immunological trafficking in peripheral blood in both renal and cardiac organ transplant rejection, across a diverse recipient age range. A common gene signature, initially identified in the setting of renal transplant rejection, can be utilized serially after cardiac transplantation, to diagnose and predict biopsy confirmed acute heart transplant rejection.
    Full-text · Article · Dec 2013 · PLoS ONE
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    ABSTRACT: There are few substantive methods to measure the health of the immune system, and the connection between immune strength and the viral component of the microbiome is poorly understood. Organ transplant recipients are treated with posttransplant therapies that combine immunosuppressive and antiviral drugs, offering a window into the effects of immune modulation on the virome. We used sequencing of cell-free DNA in plasma to investigate drug-virome interactions in a cohort of organ transplant recipients (656 samples, 96 patients) and find that antivirals and immunosuppressants strongly affect the structure of the virome in plasma. We observe marked virome compositional dynamics at the onset of the therapy and find that the total viral load increases with immunosuppression, whereas the bacterial component of the microbiome remains largely unaffected. The data provide insight into the relationship between the human virome, the state of the immune system, and the effects of pharmacological treatment and offer a potential application of the virome state to predict immunocompetence.
    Full-text · Article · Nov 2013 · Cell
  • Hannah Valantine · Christy I Sandborg
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    ABSTRACT: Central to the daily struggles that successful working women face is the misalignment of the current work culture and the values of the workforce. In addition to contributing to work-life integration conflicts, this disconnect perpetuates the gender leadership gap. The dearth of women at the highest ranks of academic medicine not only sends a clear message to women that they must choose between career advancement and their personal life but also represents a loss of talent for academic health centers as they fail to recruit and retain the best and the brightest. To close the gender leadership gap and to meet the needs of the next generation of physicians, scientists, and educators, the authors argue that the culture of academic medicine must change to one in which flexibility and work-life integration are core parts of the definition of success. Faculty must see flexibility policies, such as tenure clock extensions and parental leaves, as career advancing rather than career limiting. To achieve these goals, the authors describe the Stanford University School of Medicine Academic Biomedical Career Customization (ABCC) model. This framework includes individualized career plans, which span a faculty member's career, with options to flex up or down in research, patient care, administration, and teaching, and mentoring discussions, which ensure that faculty take full advantage of the existing policies designed to make career customization possible. The authors argue that with vision, determination, and focus, the academic medicine community can eliminate the gender leadership gap to achieve 50/50 by 2020.
    No preview · Article · Aug 2013 · Academic medicine: journal of the Association of American Medical Colleges
  • B Vrtovec · F Haddad · M Pham · T Deuse · W.F. Fearon · S Schrepfer · S Leon · T Vu · H Valantine · S.A. Hunt
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    ABSTRACT: We evaluated the potential effects of granulocyte colony-simulating factor (G- CSF) on the incidence of rejection and allograft vasculopathy in heart transplant recipients. Of 247 patients undergoing heart transplantation from 2000 to 2007, 52 (21%) developed leukopenia (white blood cell [WBC] <2.5 × 10(9)cells/L) in the absence of active infection, rejection, or malignancy. In 24 (46%) patients a clinical decision was made to treat the leukopenia with G-CSF (G-CSF group), and 28 (54%) Patients received no G-CSF (non-GCSF group). Patients followed up for 1 year after the period of leukopenia were assessed for allograft vasculopathy and acute rejection incidence. At baseline, the G-CSF group and the non-GCSF group did not differ in age, gender, race, heart failure etiology, creatinine, left ventricular ejection fraction (LVEF) or immunosupressive regimen. During 1-year follow-up there were no deaths in the G-CSF group, and 1 death in the non-GCSF group (P = .34). The incidence of rejection or progressive allograft vasculopathy was lower in the G-CSF group when compared with the non-GCSF group (2 [8%] vs 15 [53%]; P < .01). Multivariate analysis identified both prior rejection episodes and G-CSF therapy as factors associated with the combined end-point of rejection or progressive allograft vasculopathy (odds ratio [OR] = 7.89 [1.67-37.2] and OR = 0.09 [0.02-0.52], respectively). G-CSF therapy appears to be associated with a decreased incidence of acute rejection episodes or allograft vasculopathy in heart transplant recipients, suggesting a potential immunomodulatory effect of G-CSF.
    No preview · Article · Jul 2013 · Transplantation Proceedings

Publication Stats

7k Citations
1,619.16 Total Impact Points


  • 2015
    • National Institutes of Health
      베서스다, Maryland, United States
  • 1989-2015
    • Stanford University
      • • Division of Cardiovascular Medicine
      • • Department of Medicine
      • • Falk Cardiovascular Research Center
      • • Division of Infectious Diseases
      Stanford, California, United States
  • 2008
    • University of Sydney
      Sydney, New South Wales, Australia
  • 1987-2007
    • Stanford Medicine
      • • Division of Cardiovascular Medicine
      • • Division of Vascular and Endovascular Surgery
      Stanford, California, United States
  • 2002
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 2001
    • University of Wales
      Cardiff, Wales, United Kingdom
  • 1995-1998
    • University of California, Los Angeles
      • Division of Cardiology
      Los Angeles, California, United States
  • 1997
    • Universitätsspital Basel
      Bâle, Basel-City, Switzerland
  • 1992
    • St. Vincent's Hospital Sydney
      Sydney, New South Wales, Australia