Description
DEPARTMENT OF HEALTH AND HUMAN SERVICES
NATIONAL INSTITUTES OF HEALTH
NATIONAL HEART, LUNG, AND BLOOD ADVISORY COUNCIL
MEETING SUMMARY OF THE
NATIONAL HEART, LUNG, AND BLOOD ADVISORY COUNCIL
June 4, 2024
The 307th meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) convened in-person on Tuesday, June 4, 2024. The Council meeting began with a closed session that started at 8:02 a.m. and ended at 10:42 p.m. The open session reconvened from 10:54 a.m. and ended at 2:26 p.m. Dr. Gary H. Gibbons, Director of NHLBI, presided as chair.
NHLBAC Members Attending
Mercedes R. Carnethon, Ph.D.
Amanda Mae Fretts, M.D., M.P.H.
Tina V. Hartert, M.D., Ph.D.
Allison King, M.D., M.P.H., Ph.D.
Edward E. Morrisey, Ph.D.
Solomon Ofori-Acquah, Ph.D.
Merritt Raitt, M.D., Ex Officio
Lynn M. Schnapp, M.D.
Martha C. Sola-Visner, M.D.
Susan Spencer
Members of the Public Attending
The total number watching online was reported by NIH Videocast to be 281.
NHLBI Employees Attending
Several NHLBI staff members attended virtually via Zoom.
CLOSED SESSION
This portion of the meeting was closed to the public in accordance with the determination that it concerned matters exempt from mandatory disclosures under Sections 552b(c)(4) and 552b(c)(6), Title 5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act, as amended.
REVIEW OF APPLICATIONS
The session included a discussion of procedures and policies regarding voting and confidentiality of application materials, committee discussions and recommendations. Members absented themselves from the meeting during discussion of, and voting on, applications from their own institutions or other applications in which there was a potential conflict of interest, real or apparent. Members were asked to sign a statement to this effect. The Council considered and recommended 3,635 applications requesting $1,941,591,766 in total costs. For the record, it is noted that secondary applications were also considered en bloc.
OPEN SESSION
I. CALL TO ORDER
Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), called the meeting to order at 10:54 a.m. He welcomed Council members, NHLBI staff, and public attendees to the Open Session of the meeting.
II. ADMINISTRATIVE ANNOUNCEMENTS
Dr. Valerie L. Prenger (Acting Director, Division of Extramural Research Activities, NHLBI) informed attendees that the meeting would be publicly broadcast and archived on videocast. She reviewed the agenda.
III. REPORT OF THE DIRECTOR
Accountable Stewardship. Dr. Gibbons reported that NHLBI fiscal year 2024 (FY 2024) appropriations granted by Congress are unchanged from FY 2023 at $3.98 billion. Given current inflationary pressures, this calls for spending constraints. In early discussions about FY 2025, the proposed budget is expected to be similar to the prior two years.
NIH Director Dr. Monica M. Bertagnolli, at a Senate Appropriations Committee hearing about the budget, cited the following areas of focus in FY 2025: Rural health, women’s health/maternal mortality, heart disease, next generation, artificial intelligence/machine learning, Asian American and Native Hawaiian/Pacific Islanders, and the Long Covid/RECOVER Initiative.
In light of the austere budget for FY 2024, NHLBI instituted a 2% cut in non-competing awards, in order to support next generation scientists, including via early-stage investigators, career development awards, and other elements related to trainees, as well as an 8% increase in postdoctoral stipends.
Divisional News. Dr. Gibbons welcomed three new NHLBI division leaders: Drs. Traci Mondoro, Michelle Olive, and Courtney Thornburg. He also welcomed two new branch chiefs in the Division of Lung Diseases (DLD), which has made structural changes to further capture the spectrum of evolving science: Drs. Marrah Lachowicz-Scroggins and John Sheridan. He additionally welcomed Rear Admiral Richard Childs, new Scientific Director in the Division of Intramural Research. Dr. Gibbons congratulated, and made special mention of, DLD Director, Dr. James P. Kiley, for his 40 years of service in advancing the NHLBI mission.
Scientific Opportunities. Dr. Gibbons gave an update on some of NHLBI’s research opportunities. The strategic vision refresh is progressing, incorporating diverse perspectives, and developing 26 new critical challenges and six new compelling questions.
Sickle Cell Disease. Dr. Gibbons cited NHLBI’s progress in turning discovery into curative therapies for rare diseases, for instance through the Cure Sickle Cell initiative. The FDA approved gene therapies for Sickle Cell Disease (SCD) and researchers found that treating severe SCD with BCL 11A eliminated vaso-occlusive events. He noted that Sickle Cell Branch Chief Swee Lay Thein received the Shaw Prize in Life Science and Medicine, 2024.
Dr. Gibbons also discussed the Catalyze program, which supports the translation of discoveries at scale via commercialization.
He mentioned the potential opportunities offered by the White House Initiative on Women’s Health, to produce more research in women’s health across the lifespan. For instance, the cardiovascular disease (CVD) risk profile is different in women from men, and a better understanding of menopause and vasomotor symptoms, such as hot flashes, as well as mechanisms underlying CVD risk, could lead to new targeted therapies.
Idiopathic Lung Disease. Dr. Gibbons noted that part of the strategic plan refresh is to better understand the molecular basis of chronic lung disease. Idiopathic pulmonary fibrosis is one of the areas of unmet need and NHLBI scientists are working to elucidate the molecular mechanisms of lung fibrosis in a novel mouse model of conditional cell senescence. Intriguingly, selectively targeting senescent cells resulted in enhanced lung fibrosis, giving important insight into lung function. Familial pulmonary models can help in the identification of new, relevant genes and pathways that mediate disease risk.
Dr. Gibbons cited emerging opportunities for radiomics and deep learning for phenotypic, clinical, molecular, and prognostic characterization of idiopathic lung disease. Research in this area might produce subtle, preclinical biomarkers for some of the disease processes. Investigators have begun revealing genetic and environmental risk factors for early radiologic interstitial lung abnormalities. Several other studies are underway to better understand the disease in the preclinical context, its pathogenesis, and genetic contributors, which will hopefully lead to new therapeutics.
He discussed the application of machine learning (ML) and artificial intelligence (AI) to imaging. The implications of these technologies for clinical medicine over the next 5-10 years are likely to be profound and the NHLBI needs to incorporate ML and AI investments in its portfolio.
Dr. Gibbons concluded his talk and thanked everyone for their attention.
IV. CLONAL HEMATOPOIESIS FOLLOWING CURATIVE THERAPIES FOR SICKLE CELL DISEASE
Dr. Courtney Fitzhugh, Lasker Clinical Research Scholar, Laboratory of Early Sickle Mortality Prevention, NHLBI
Dr. Fitzhugh presented on Sickle Cell Disease (SCD) treatments and associated comorbidities. Her research includes exploring new avenues for hematopoietic cell transplantation (HCT) for SCD and the long-term health effects of curative therapies.
Dr. Fitzhugh noted that in patients with SCD, the median survival is 48 years. Lung, kidney, or heart impairments raise the risk of early death. Patients also face a higher risk of acute myeloid malignancies and scientists are investigating why, including the role of clonal hematopoiesis (CH), a premalignant condition with somatic mutations that can lead to blood cancers.
She discussed several studies of patients with SCD and their findings. One identified an increased risk of 2.3-fold for leukemia and 3.6-fold for acute myeloid leukemia, with the risk higher for those who were older or had more severe SCD. Hydroxyurea treatment was not a risk factor.
Another study examined patients who underwent myeloablative HLA-matched sibling HCT. The 5-year event-free survival was 91.4%, but 14.3% had chronic graft-versus-host disease (GVDH).
A new approach avoided chemotherapy before HCT but instead suppressed the immune system with Alemtuzumab, radiation, and Sirolimus. However, in a study of 120 patients who underwent a nonmyeloablative HCT, 5 developed aggressive myeloid malignancies later, after GVDH.
Dr. Fitzhugh then discussed autologous gene therapy strategies, which are another curative option for SCD but also show a risk of aggressive myeloid malignancies. She and her team found that in most patients who developed these malignancies, pathogenic TP53 mutations were present before curative therapies. Controls without the mutations typically did not develop myeloid malignancies.
Further studies found that SCD status was independently associated with an increase in CH, especially in older individuals and patients with severe disease. Dr. Fitzhugh is studying how this might happen and how to mitigate the risk.
The absolute risk of aggressive myeloid malignancies remains low but is significantly higher in adults following HCT and graft failure, or gene therapy, compared with patients who do not receive curative therapies. The presence of CH may guide therapeutic decisions in patients with SCD, for instance, preferring mixed donor/recipient chimerism to full donor chimerism and changing the dosage of immunosuppression, Dr. Fitzhugh concluded.
V. NHLBI CONCEPT CLEARANCE
NHLBI staff presented 16 concepts for clearance. Members of the Advisory Council were asked to rate each concept on six criteria using Decision Lens.
Titles: Viral Infections in the Young Lung-The VINYL Clinical Consortium (UG3, UH3). Viral Infections in the Young Lung-The VINYL Clinical Consortium (U24)
Description: These concepts aim to build a new consortium focused on lower respiratory tract viral infections, which annually cause many hospitalizations, especially of young children, who can suffer long-term impact on lung and airway health. The RFAs will establish coordination centers and conduct extensive deep phenotyping and follow-up in a cohort of 1,500 very young children into preschool years.
Title: National Sleep Research Resource (NSRR) (N01)
Description: This contract renewal continues this highly accessed resource, currently with 11,000 users worldwide and 18 funded projects across NIH that focus on sleep and circadian research. The renewal will add new datasets and facilitate hypotheses with AI and ML approaches.
Title: Short-Term Research Experience Program to Unlock Potential (STEP-UP) (R25 Clinical Trial not allowed)
Description: This concept enables NHLBI to participate as a secondary sign-on in an NIH-wide initiative led by NIDDK. STEP-UP supports short-term research experiences for high school-level students, to attract them into research careers and help grow a diverse biomedical workforce. Established in 2002, STEP-UP has coordinating centers in geographically neglected U.S. areas and annually matches mentors and 25 high school students for an 8-week internship.
Title: Bench to Bassinet Congenital Heart Disease Advancing New Understanding in Genomics Cohort (B28 CHANGE Cohort) (U01)
Description: This concept renews support of a cohort that has increased understanding of congenital heart disease genetics and identified the origin of 25% of previously unexplained disease. Continuing this large cohort would allow long-term follow-up of participants, to assess clinical outcomes and encourage mechanistic studies.
Title: Global Cardiovascular Research Funders Forum/Women’s Cardiovascular Health Research Initiative (WCHR) (Other)
Description: This concept would enable funding of women’s CV health research through a consortium of 12 major CV research groups in the United States, Canada, Australia, and New Zealand. NHLBI’s contribution for the $10-million, 5-year program would be $1.9 million. The FY 2026 award is expected to be multi-disciplinary, multi-institutional, and multi-country. The lead institution can partner outside the consortium.
Title: Renewal of the MACS/WIHS Combined Cohort Study (MWCCS) of HIV in the United States (U01)
Description: This concept renews support for NHLBI’s participation in MWCCS for another 7 years. In 2019, the NIH merged two long-standing HIV-based cohorts and reoriented them to study long-term survival of men and women living with HIV/AIDS. Several key areas of science will be expanded to account for evolving HIV knowledge and aging of the cohorts.
Title: Stimulating Access to Research in Residency (StARR) Program Renewal (R38)
Description: This concept renews support for this research in residency program, for which NHLBI is the lead institute, with participation from NIAID, NCI, NIA, and NEI, among others. This program is designed to develop more physician-scientists, to engage in research. Residents are supported for between 12 and 24 months.
Title: Whole Person Research and Coordination Center (Whole Person RCC) (U24)
Description: This concept renews secondary NHLBI participation in an NIH-wide program led by NCCIH. The goal is to build an integrated framework covering research ranging from molecular studies to patient, cultural, and societal level data. NHLBI will contribute $100,000 per year for 5 years, which is 4% of the project’s overall budget.
Titles: NHLBI SBIR Phase IIB Bridge Awards to Accelerate the Commercialization of Technologies for Heart, Lung, Blood and Sleep Disorders and Diseases (R44). NHLBI SBIR Phase IIB Small Market Awards to Accelerate the Commercialization of Technologies for Heart, Lung, Blood and Sleep Disorders and Diseases (R44)
Description: These two concepts renew support for the commercialization of technologies that can help NHLBI-related conditions. These awards are particularly important in the current environment because external funders have become increasingly risk adverse.
Titles: Catalyze Enabling Technologies Transformative Platforms (R33). Catalyze: Product Definition for Small Molecules and Biologics – Target Identification and Validation, and Preliminary Product/Lead Series Identification (R61/R33 – Clinical Trials Not Allowed). Catalyze: Product Definition for Small Molecules and Biologics – Preliminary Product/Lead Series Identification (R33 – Clinical Trials Not Allowed). Catalyze Product Definition – Medical Device Prototype Design/Testing and Disease Target Identification and Assay Development (R61/R33). Catalyze: Product Definition – Medical Device Prototype Testing, Design Modification, Characterization and Validation (R33 – Clinical Trials Not Allowed)
Description: These concepts renew funding for a suite of programs, supports, and services, to efficiently and effectively help investigators bring their NHLBI-related innovations from the product definition stage through clinical research and regulatory submissions. The program, launched 5 years ago, has attracted 253 applications, funded 51, and led to 60 publications, 23 U.S. patent applications, and six international patent applications.
VI. CLOSING REMARKS
Dr. Gibbons adjourned the meeting at 2:26 p.m.
CERTIFICATION
I hereby certify that the foregoing minutes are accurate and complete.