Proteomics in Acute Heart Transplant Rejection, On Behalf of the GRAfT Investigators.

Background: Proteomic phenotyping can provide insights into rejection pathophysiology, novel biomarkers, and therapeutic targets.

Methods: Within the prospective, multicenter Genomic Research Alliance for Transplantation study, 181 proteins were evaluated from blood drawn at the time of endomyocardial biopsy; protein fold change, logistic regression, and pathway analyses were conducted, with protein discovery adjusted for a 5% false discovery rate.

Results: Among 104 adult heart transplant patients (31% female sex, 53% Black race, median age 52 y), 74 had no rejection, 18 developed acute cellular rejection (ACR), and 12 developed antibody-mediated rejection (AMR).

Pathologist interrater reliability and clinical implications of elevated donor-derived cell-free DNA beyond heart transplant rejection, on behalf of the GRAfT investigators.

Background: There is significant variability among pathologists in the histopathological interpretation of the endomyocardial biopsy (EMB) for acute cellular rejection (ACR), and assessment of variability in the interpretation of antibody-mediated rejection (AMR) has not been reported. In contemporary practice, the strategy of allograft surveillance with donor-derived cell-free DNA (dd-cfDNA) compared to EMB has not been compared with a focus on long-term clinical outcomes beyond acute rejection (AR).

Methods: The Genomic Research Alliance for Transplantation is a multicenter, prospective cohort study that enrolled patients from 2015 to 2020.

Sex-specific patterns of donor-derived cell-free DNA in heart transplant rejection: An analysis from the Genomic Research Alliance for Transplantation (GRAfT).

Background: Noninvasive methods for surveillance of acute rejection are increasingly used in heart transplantation (HT), including donor-derived cell-free DNA (dd-cfDNA). As other cardiac biomarkers differ by sex, we hypothesized that there may be sex-specific differences in the performance of dd-cfDNA for the detection of acute rejection. The purpose of the current study was to examine patterns of dd-cfDNA seen in quiescence and acute rejection in male and female transplant recipients.

Racial Differences in Donor-Derived Cell-Free DNA and Mitochondrial DNA After Heart Transplantation, on Behalf of the GRAfT Investigators.

Background: Black heart transplant patients are at higher risk of acute rejection (AR) and death than White patients. We hypothesized that this risk may be associated with higher levels of donor-derived cell-free DNA (dd-cfDNA) and cell-free mitochondrial DNA.

Methods: The Genomic Research Alliance for Transplantation is a multicenter, prospective, longitudinal cohort study.

Neural responses to gender-based microaggressions in academic medicine.

Gender-based microaggressions have been associated with persistent disparities between women and men in academia. Little is known about the neural mechanisms underlying those often subtle and unintentional yet detrimental behaviors. Here, we assessed the neural responses to gender-based microaggressions in 28 early career faculty in medicine (N = 16 female, N = 12 male sex) using fMRI.

Hannah A. Valantine, M.D., Stanford University School of Medicine.

Dr. Hannah Valantine is renowned for her work in transplantation medicine, leadership, and mentoring as well as her efforts to improve scientific workforce diversity. In this interview with Cell, she discusses her research; what Juneteenth means to her; the persistent gender, race, and ethnicity leadership gaps that exist in academic medicine; and the importance of equitable, inclusive, and diverse science.

Applying Genomics to Unravel Health Disparities in Organ Transplantation: Paul I. Terasaki State-of-the-art Lecture; American Transplant Congress 2021.

An extensive body of research about team science provides empirical evidence that diverse teams outperform homogenous teams in creating more innovative solutions to complex problems. At the core of diverse and inclusive teams is a rich diversity of perspectives, experiences, and backgrounds that invite new questions and broaden the scope of research. Diverse perspectives are especially relevant for biomedicine, which seeks to find solutions for challenging problems affecting the human condition.

Plasma Cell-Free DNA Predicts Survival and Maps Specific Sources of Injury in Pulmonary Arterial Hypertension.

Background: Cell-free DNA (cfDNA) is a noninvasive marker of cellular injury. Its significance in pulmonary arterial hypertension (PAH) is unknown.

Methods: Plasma cfDNA was measured in 2 PAH cohorts (A, n=48; B, n=161) and controls (n=48).

Circulating microRNAs in cellular and antibody-mediated heart transplant rejection.

Background: Noninvasive monitoring of heart allograft health is important to improve clinical outcomes. MicroRNAs (miRs) are promising biomarkers of cardiovascular disease and limited studies suggest they can be used to noninvasively diagnose acute heart transplant rejection.

Methods: The Genomic Research Alliance for Transplantation (GRAfT) is a multicenter prospective cohort study that phenotyped heart transplant patients from 5 mid-Atlantic centers.

Higher levels of allograft injury in black patients early after heart transplantation.

Black patients suffer higher rates of antibody-mediated rejection and have worse long-term graft survival after heart transplantation. Donor-derived cell free DNA (ddcfDNA) is released into the blood following allograft injury. This study analyzed %ddcfDNA in 63 heart transplant recipients categorized by Black and non-Black race, during the first 200 days after transplant.

Ending Sexual Harassment in Science: Designing and Administering a Survey That Can Lead to an Improved Organizational Climate.

Workplace harassment, particularly sexual harassment, has substantial negative implications for individuals and organizations and for scientific advancement. The National Institutes of Health (NIH) is uniquely positioned to lead the effort to prevent sexual harassment in the scientific community and mitigate its detrimental effects. Recognizing the need for benchmark data, NIH developed and validated the 2019 NIH Workplace Climate and Harassment Survey.

Donor derived cell free DNA% is elevated with pathogens that are risk factors for acute and chronic lung allograft injury.

Background: Acute and chronic forms of lung allograft injury are associated with specific respiratory pathogens. Donor-derived cell free DNA (ddcfDNA) has been shown to be elevated with acute lung allograft injury and predictive of long-term outcomes. We examined the %ddcfDNA values at times of microbial isolation from bronchoalveolar lavage (BAL).

The COVID-19 Vaccine and the Black Community: Addressing the Justified Questions.

Established in 2019, the Roundtable on Black Men and Black Women in STEM convenes a broad array of stakeholders that focus on the barriers and opportunities encountered by Black men and Black women as they navigate the pathways from K-12 and postsecondary education to careers in science, engineering, and medicine. Through meetings, public workshops, and publications, the Roundtable advances discussions that raise awareness and/or highlight promising practices for increasing the representation, retention, and inclusiveness of Black men and Black women in STEM. In keeping with the charge of the Roundtable, Roundtable leadership and leaders of the COVID-19 action group conducted an informational video in January 2021 to provide an in-depth discussion around common, justified questions in the Black community pertaining to the COVID-19 vaccine.

Applications of genetic-epigenetic tissue mapping for plasma DNA in prenatal testing, transplantation and oncology.

We developed genetic-epigenetic tissue mapping (GETMap) to determine the tissue composition of plasma DNA carrying genetic variants not present in the constitutional genome through comparing their methylation profiles with relevant tissues. We validated this approach by showing that, in pregnant women, circulating DNA carrying fetal-specific alleles was entirely placenta-derived. In lung transplant recipients, we showed that, at 72 hr after transplantation, the lung contributed only a median of 17% to the plasma DNA carrying donor-specific alleles, and hematopoietic cells contributed a median of 78%.