Implementing systems thinking and data science in the training of the regenerative medicine workforce.

was organized by the National Academies of Sciences, Engineering, and Medicine’s Forum on Regenerative Medicine. The meeting brought together leaders from government, academia, industry, professional associations, foundations, patient communities, and other stakeholder groups to address the potential for cross-disciplinary systems thinking to advance regenerative medicine. Discussions during the meeting covered the role of data science in regenerative medicine and the importance of data science training and data literacy for the current and future regenerative medicine workforce.

The National Academies' Roundtable on Genomics and Precision Health: Where we have been and where we are heading.

The clinical application of genetics and genomics to advance precision health is one of the most dynamic and promising areas of medicine. In 2020, building on nearly 15 years of work, the Roundtable on Genomics and Precision Health of the National Academies of Sciences, Engineering, and Medicine undertook a strategic planning process to assess its strengths, consider the current challenges facing the field, and set out new goals for its future work. As a result, the Roundtable has updated its vision and mission and prioritized four major areas of inquiry-innovation, dialogue, equity, and adoption-while keeping true to its founding goal of providing a neutral convening space for the diversity of stakeholders in genomics and precision health.

Implementing Cancer Genomics in State Health Agencies: Mapping Activities to an Implementation Science Outcome Framework.

Objective: To show how state health agencies can plan and evaluate activities to strengthen the evidence base for public health genomics, we mapped state cancer genomics activities to the Doyle et al. [Genet Med. 2018;20(9):995-1003] implementation science outcome framework.

Tumor priming by Apo2L/TRAIL reduces interstitial fluid pressure and enhances efficacy of liposomal gemcitabine in a patient derived xenograft tumor model.

Interstitial fluid pressure (IFP) is elevated in tumors and high IFP, a negative cancer prognosticator, is known to limit the uptake and efficacy of anti-tumor therapeutics. Approaches that alter the tumor microenvironment and enhance uptake of therapeutics are collectively referred to as tumor "priming". Here we show that the cytotoxic biological therapy Apo2L/TRAIL can prime the tumor microenvironment and significantly lower IFP in three different human tumor xenograft models (Colo205, MiaPaca-2 and a patient gastrointestinal adenocarcinoma tumor xenograft).

Isolated Hoxa9 overexpression predisposes to the development of lymphoid but not myeloid leukemia.

Hoxa9 is expressed in hematopoietic stem and progenitor cells, although this expression is usually diminished as these cells undergo differentiation. In addition, aberrant expression of Hoxa9 is strongly associated with both T cell and myeloid leukemia in mice and humans. Despite this strong association, enforced expression of Hoxa9 in murine bone marrow or thymus has only shown a modest ability to transform cells.

Gene expression profiling and candidate gene resequencing identifies pathways and mutations important for malignant transformation caused by leukemogenic fusion genes.

NUP98-HOXD13 (NHD13) and CALM-AF10 (CA10) are oncogenic fusion proteins produced by recurrent chromosomal translocations in patients with acute myeloid leukemia (AML). Transgenic mice that express these fusions develop AML with a long latency and incomplete penetrance, suggesting that collaborating genetic events are required for leukemic transformation. We employed genetic techniques to identify both preleukemic abnormalities in healthy transgenic mice as well as collaborating events leading to leukemic transformation.

Enforced expression of Lin28b leads to impaired T-cell development, release of inflammatory cytokines, and peripheral T-cell lymphoma.

LIN28A and LIN28B, the mammalian homologs of lin-28, are implicated in malignant transformation in part because of their ability to promote degradation of the let-7 family of miRs. In the present study, we show that overexpression of Lin28b in vivo leads to an aggressive peripheral T-cell lymphoma (PTCL) characterized by widespread infiltration of parenchymal organs with malignant CD4(+) cells. Similar to patients with PTCL, Lin28b-transgenic mice show signs of inflammation such as eosinophilia, increased C-reactive protein, release of inflammatory cytokines, and pleural effusion.

Toward establishment of temperature thresholds for immunological impact of heat exposure in humans.

There is interest in understanding the health impact of thermal effects as a result of exposure of humans to radiofrequency/microwave (RF/MW) fields. Immune cells and responses are affected by modest changes in temperature and it is important to quantify these effects and establish safety thresholds similar to what has been done with other tissue targets. Since previous summaries of thresholds for thermal damage to normal tissues have not focused much attention to cells of the immune system, this summary highlights recent studies which demonstrate positive and some negative effects of temperature shifts on human immune cells.

Mouse models of myelodysplastic syndromes.

Three general approaches have been used to model myelodysplastic syndrome (MDS) in mice, including treatment with mutagens or carcinogens, xenotransplantation of human MDS cells, and genetic engineering of mouse hematopoietic cells. This article discusses the phenotypes observed in available mouse models for MDS with a concentration on a model that leads to aberrant expression of conserved homeobox genes that are important regulators of normal hematopoiesis. Using these models of MDS should allow a more complete understanding of the disease process and provide a platform for preclinical testing of therapeutic approaches.

Dissecting the role of hyperthermia in natural killer cell mediated anti-tumor responses.

The effects of hyperthermia on natural killer (NK) cell cytotoxicity against tumor cell targets are not yet fully understood. A more complete understanding of these effects could be important for maximizing the clinical benefits obtained by using hyperthermia for cancer therapy. Here, we summarize results in the literature regarding the effects of elevated temperatures on NK cells and our own recent data on the effects of fever-range temperatures.

The tetraspanin superfamily member NET-6 is a new tumor suppressor gene.

Purpose: NET-6 is a largely uncharacterized member of the tetraspanin superfamily. We have recently shown that its expression level was lowest in breast carcinomas with aggressive characteristics. We now describe the phenotypic and molecular changes induced in MDA-MB-231 breast carcinoma cells by ectopic NET-6 expression.