Not Dead Yet.

I have been a scientific grasshopper throughout my career, moving from question to question within the domain of lupus. This has proven to be immensely gratifying. Scientific exploration is endlessly fascinating, and succeeding in studies you care about with colleagues and trainees leads to strong and lasting bonds. Science isn't easy; being a woman in science presents challenges, but the drive to understand a disease remains strong.

A Perspective on the Role of Computational Models in Immunology.

This is an exciting time for immunology because the future promises to be replete with exciting new discoveries that can be translated to improve health and treat disease in novel ways. Immunologists are attempting to answer increasingly complex questions concerning phenomena that range from the genetic, molecular, and cellular scales to that of organs, whole animals or humans, and populations of humans and pathogens. An important goal is to understand how the many different components involved interact with each other within and across these scales for immune responses to emerge, and how aberrant regulation of these processes causes disease. To aid this quest, large amounts of data can be collected using high-throughput instrumentation. The nonlinear, cooperative, and stochastic character of the interactions between components of the immune system as well as the overwhelming amounts of data can make it difficult to intuit patterns in the data or a mechanistic understanding of the phenomena being studied. Computational models are increasingly important in confronting and overcoming these challenges. I first describe an iterative paradigm of research that integrates laboratory experiments, clinical data, computational inference, and mechanistic computational models. I then illustrate this paradigm with a few examples from the recent literature that make vivid the power of bringing together diverse types of computational models with experimental and clinical studies to fruitfully interrogate the immune system.

The history of sex research: Is "sex" a useful category?

The history of sex research demonstrates an ongoing coexistence of multiple, conflicting meanings of sex. This history raises questions for scientists about the deployment of a research variable that lacks precision. Cross-disciplinary collaboration between scientists and science and technology studies (STS) scholars offers a way to find solutions to this problem.

Sex contextualism in laboratory research: Enhancing rigor and precision in the study of sex-related variables.

Understanding sex-related variation in health and illness requires rigorous and precise approaches to revealing underlying mechanisms. A first step is to recognize that sex is not in and of itself a causal mechanism; rather, it is a classification system comprising a set of categories, usually assigned according to a range of varying traits. Moving beyond sex as a system of classification to working with concrete and measurable sex-related variables is necessary for precision. Whether and how these sex-related variables matter-and what patterns of difference they contribute to-will vary in context-specific ways. Second, when researchers incorporate these sex-related variables into research designs, rigorous analytical methods are needed to allow strongly supported conclusions. Third, the interpretation and reporting of sex-related variation require care to ensure that basic and preclinical research advance health equity for all.

The future of sex and gender in research.

Our understanding of sex and gender evolves. We asked scientists about their work and the future of sex and gender research. They discuss, among other things, interdisciplinary collaboration, moving beyond binary conceptualizations, accounting for intersecting factors, reproductive strategies, expanding research on sex-related differences, and sex's dynamic nature.

50 years of metabolism research at Cell.

This 50th Anniversary Focus on Metabolism highlights several foundational and current themes of interest in metabolism research.

Ending "domestic helicopter research".

"Helicopter research" refers to a practice where researchers from wealthier countries conduct studies in lower-income countries with little involvement of local researchers or community members. This practice also occurs domestically. In this Commentary, we outline strategies to curb domestic helicopter research and to foster equity-centered collaborations.

Bridge-building between communities: Imagining the future of biomedical autism research.

A paradigm shift in research culture is required to ease perceived tensions between autistic people and the biomedical research community. As a group of autistic and non-autistic scientists and stakeholders, we contend that through participatory research, we can reject a deficit-based conceptualization of autism while building a shared vision for a neurodiversity-affirmative biomedical research paradigm.

The power of hope.

My patient was in his late 20s and dying of an advanced sarcoma. He came to our institution seeking a miracle-a cure for his incurable cancer. Despite second and third opinions, he never relinquished his hope that science would cure him. In this story, I explore how hope allowed my patient, and others like him, to reclaim their narratives and maintain their personhood in the face of serious illness.

Metalloproteomics for Biomedical Research: Methodology and Applications.

Metals are essential components in life processes and participate in many important biological processes. Dysregulation of metal homeostasis is correlated with many diseases. Metals are also frequently incorporated into diagnosis and therapeutics. Understanding of metal homeostasis under (patho)physiological conditions and the molecular mechanisms of action of metallodrugs in biological systems has positive impacts on human health. As an emerging interdisciplinary area of research, metalloproteomics involves investigating metal-protein interactions in biological systems at a proteome-wide scale, has received growing attention, and has been implemented into metal-related research. In this review, we summarize the recent advances in metalloproteomics methodologies and applications. We also highlight emerging single-cell metalloproteomics, including time-resolved inductively coupled plasma mass spectrometry, mass cytometry, and secondary ion mass spectrometry. Finally, we discuss future perspectives in metalloproteomics, aiming to attract more original research to develop more advanced methodologies, which could be utilized rapidly by biochemists or biologists to expand our knowledge of how metal functions in biology and medicine.

Basic science under threat: Lessons from the Skirball Institute.

Support for basic science has been eclipsed by initiatives aimed at specific medical problems. The latest example is the dismantling of the Skirball Institute at NYU School of Medicine. Here, we reflect on the achievements and mission underlying the Skirball to gain insight into the dividends of maintaining a basic science vision within the academic enterprises.

Cell maturation: Hallmarks, triggers, and manipulation.

How cells become specialized, or "mature," is important for cell and developmental biology. While maturity is usually deemed a terminal fate, it may be more helpful to consider maturation not as a switch but as a dynamic continuum of adaptive phenotypic states set by genetic and environment programing. The hallmarks of maturity comprise changes in anatomy (form, gene circuitry, and interconnectivity) and physiology (function, rhythms, and proliferation) that confer adaptive behavior. We discuss efforts to harness their chemical (nutrients, oxygen, and growth factors) and physical (mechanical, spatial, and electrical) triggers in vitro and in vivo and how maturation strategies may support disease research and regenerative medicine.

Celebrating scientific excellence and global health impact: The 2022 Canada Gairdner Awards.

From mRNA vaccines to community interventions in global child health, the 2022 Canada Gairdner awards demonstrate the importance of fundamental science and its translation into improved human health and well-being.

Precision medicine requires understanding how both sex and gender influence health.

Progress in studying sex as a biological variable (SABV) is slow, and the influence of gendered effects of the social environment on biology is largely unknown. Yet incorporating these concepts into basic science research will enhance our understanding of human health and disease. We provide steps to move this process forward.

Before you call the midwife.

The 2022 Lasker-DeBakey Clinical Medical Research Award is presented to Yuk Ming Dennis Lo of the Chinese University of Hong Kong for the discovery of fetal DNA in maternal blood, leading to development of noninvasive prenatal testing for Down syndrome.

Underrepresentation of Asian awardees of United States biomedical research prizes.

The lack of racial diversity among the winners of United States biomedical research prizes reflects a chronic problem of the underappreciation of certain groups of biomedical scientists. Asians continue to be severely underrepresented as awardees of United States biomedical research prizes, a trend that shows no obvious recent improvement.

Cancer stem cells: The adventurous journey from hematopoietic to leukemic stem cells.

This year's Gairdner Foundation Award for Biomedical Research is awarded to John Dick for the discovery of leukemic stem cells and the hierarchical organization of acute myeloid leukemias. His work laid the foundation for the cancer stem cell model with numerous clinical implications for hematopoietic malignancies and solid tumors.

Francis Collins: Reflections on being the NIH Director.

For over 12 years, spanning three administrations, Dr. Francis Collins has served as the director of the National Institutes of Health. During that time, he and the NIH launched ambitious programs to spur research in diverse topic areas, with important successes. He has also confronted issues facing science and scientists. Dr. Collins recently stepped down as director. Before his departure, he had a conversation with John Pham, reflecting on his time leading the NIH and sharing his perspectives and his hopes for the NIH and the scientific community moving forward.

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.

Affirming NIH's commitment to addressing structural racism in the biomedical research enterprise.

NIH has acknowledged and committed to ending structural racism. The framework for NIH's approach, summarized here, includes understanding barriers; developing robust health disparities/equity research; improving its internal culture; being transparent and accountable; and changing the extramural ecosystem so that diversity, equity, and inclusion are reflected in funded research and the biomedical workforce.