Afshin Beheshti

University of Pittsburgh | Pitt · Center of Space Biomedicine and McGowan Institute for Regenerative Medicine and Department Surgery

Lethal COVID-19 outcomes are attributed to classic cytokine storm. We revisit this using RNA sequencing of nasopharyngeal and 40 autopsy samples from patients dying of SARS-CoV-2. Subsets of the 100 top-upregulated genes in nasal swabs are upregulated in the heart, lung, kidney, and liver, but not mediastinal lymph nodes. Twenty-two of these are “n...

Breast cancer is the second most common cancer globally. Most deaths from breast cancer are due to metastatic disease which often follows long periods of clinical dormancy. Understanding the mechanisms that disrupt the quiescence of dormant disseminated cancer cells (DCC) is crucial for addressing metastatic progression. Infection with respiratory...

To be able to understand how spaceflight can affect human biology, there is a need for maximizing the amount of information that can be obtained from experiments flown to space. Recently there has been an influx of data obtained from astronauts through multi-omics approaches based on both governmental and commercial spaceflight missions. In additio...

Bone loss, commonly seen in osteoporosis, is a condition that entails a progressive decline of bone mineral density and microarchitecture, often seen in post-menopausal women. Bone loss has also been widely reported in astronauts exposed to a plethora of stressors and in patients with osteoporosis following radiotherapy for cancer. Studies on mecha...

MicroRNAs (miRNAs) have been implicated in human disorders, from cancers to infectious diseases. Targeting miRNAs or their target genes with small molecules offers opportunities to modulate dysregulated cellular processes linked to diseases. Yet, predicting small molecules associated with miRNAs remains challenging due to the small size of small mo...

In the era of renewed space exploration, comprehending the effects of the space environment on human health, particularly for deep space missions, is crucial. While extensive research exists on the impacts of spaceflight, there is a gap regarding female reproductive risks. We hypothesize that space stressors could have enduring effects on female he...

The possibility of impaired cognitive function during deep space flight missions or while living on a Martian colony is a critical point of concern and pleads for further research. In addition, a fundamental gap exists both in our understanding and application of countermeasures for the consequences of long duration space travel and/or living in an...

A meta-analysis of spaceflight data from both mouse and human flights reveals a striking overlap with Parkinson's disease (PD). Parallels include: changes in gait, loss of dopamine, sustained changes in the basal ganglia, loss of tyrosine hydroxylase in the substantia nigra, and systemic mitochondrial dysfunction. We identified specific Parkinson's...

Adenosine to inosine (A-to-I) RNA editing by ADAR1 has been implicated in maintaining self-tolerance, preventing autoimmunity, and mediating antiviral immunity. Foreign viral double-stranded RNA triggers rapid interferon response and activates ADAR1 in the host immune system. Emerging data points to a role of ADAR1 A-to-I editing in the inflammator...

Organismal adaptations to spaceflight have been characterized at the molecular level in model organisms, including Drosophila and C. elegans. Here, we extend molecular work to energy metabolism and sex hormone signaling in mice and humans. We found spaceflight induced changes in insulin and estrogen signaling in rodents and humans. Murine changes w...

The recent acceleration of commercial, private, and multi-national spaceflight has created an unprecedented level of activity in low Earth orbit (LEO), concomitant with the highest-ever number of crewed missions entering space and preparations for exploration-class (>1 year) missions. Such rapid advancement into space from many new companies, count...

It is now widely recognised that the environment in space activates a diverse set of genes involved in regulating fundamental cellular pathways. This includes the activation of genes associated with blood homeostasis and erythropoiesis, with a particular emphasis on those involved in globin chain production. Haemoglobin biology provides an intrigui...

As spaceflight becomes more common with commercial crews, blood-based measures of crew health can guide both astronaut biomedicine and countermeasures. By profiling plasma proteins, metabolites, and extracellular vesicles/particles (EVPs) from the SpaceX Inspiration4 crew, we generated “spaceflight secretome profiles,” which showed significant diff...

Our previous research revealed a key microRNA signature that is associated with spaceflight that can be used as a biomarker and to develop countermeasure treatments to mitigate the damage caused by space radiation. Here, we expand on this work to determine the biological factors rescued by the countermeasure treatment. We performed RNA-sequencing a...

Microgravity is associated with immunological dysfunction, though the mechanisms are poorly understood. Here, using single-cell analysis of human peripheral blood mononuclear cells (PBMCs) exposed to short term (25 hours) simulated microgravity, we characterize altered genes and pathways at basal and stimulated states with a Toll-like Receptor-7/8...

Spaceflight can change metabolic, immunological, and biological homeostasis and cause skin rashes and irritation, yet the molecular basis remains unclear. To investigate the impact of short-duration spaceflight on the skin, we conducted skin biopsies on the Inspiration4 crew members before (L-44) and after (R + 1) flight. Leveraging multi-omics ass...

Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney are largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic),...

Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew. We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight....

Human space exploration poses inherent risks to astronauts’ health, leading to molecular changes that can significantly impact their well-being. These alterations encompass genomic instability, mitochondrial dysfunction, increased inflammation, homeostatic dysregulation, and various epigenomic changes. Remarkably, these changes bear similarities to...

Background Spaceflight poses a unique set of challenges to humans and the hostile spaceflight environment can induce a wide range of increased health risks, including dermatological issues. The biology driving the frequency of skin issues in astronauts is currently not well understood. Methods To address this issue, we used a systems biology appro...

Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space1–6. Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring...

Human spaceflight has historically been managed by government agencies, such as in the NASA Twins Study¹, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first all-civilian crew to low Earth orbit, which included the youngest American astronaut (aged...

As the space industry grows exponentially and aspirations for space travel expand, we are entering a new era where we will very likely become an interplanetary species. Although reproduction is an essential human function and necessary for species survival, we have remarkably little knowledge regarding the impact of space travel on the female repro...

Purpose: Two-photon microscopy (2PM) is an emerging clinical imaging modality with the potential to non-invasively assess tissue metabolism and morphology in high-resolution. This study aimed to assess the translational potential of 2PM for improved detection of high-grade cervical precancerous lesions. Experimental Design: 2P images attributed to...

With ongoing global research efforts to tackle coronavirus disease 2019 (COVID-19), increasing attention is directed toward the long-term sequelae of COVID, entitled “long COVID” or post-acute sequelae of COVID-19. These long-COVID symptoms persist beyond 12 weeks in over 10%–40% of patients, with exertional fatigue predominant in at least 50%. Sci...

In the era of renewed space exploration, comprehending the effects of the space environment on human health, particularly for deep space missions, is crucial. While extensive research exists on the impacts of spaceflight, there is a gap regarding female reproductive risks. We hypothesize that space stressors could have enduring effects on female he...

Breast cancer is the second most common cancer globally. Most deaths from breast cancer are due to metastatic disease which often follows long periods of clinical dormancy ¹ . Understanding the mechanisms that disrupt the quiescence of dormant disseminated cancer cells (DCC) is crucial for addressing metastatic progression. Infection with respirato...

To explore new worlds we must ensure humans can survive and thrive in the space environment. Incidence of kidney stones in astronauts is a major risk factor associated with long term missions, caused by increased blood calcium levels due to bone demineralisation triggered by microgravity and space radiation. Transcriptomic changes have been observe...

Species-specific genes are ubiquitous in evolution, with functions ranging from prey paralysis to survival in subzero temperatures. Because they are typically expressed under limited conditions and lack canonical features, such genes may be vastly under-identified, even in humans. Here, we leverage terabytes of human RNA-Seq data to identify thousa...

Breast cancer (BC) is one of the most commonly diagnosed cancers worldwide. As key regulatory molecules in several biological processes, microRNAs (miRNAs) are potential biomarkers for cancer. Understanding the miRNA markers that can detect BC may improve survival rates and develop new targeted therapeutic strategies. To identify a circulating miRN...

Despite surging interest in space travel in recent decades, the impacts of prolonged, elevated exposure to galactic cosmic radiation (GCR) on human health remain poorly understood. This form of ionizing radiation causes significant changes to biological systems including damage to DNA structure by altering epigenetic phenotype with emphasis on DNA...

The orphan gene of SARS-CoV-2, ORF10, is the least stud- ied gene in the virus responsible for the COVID-19 pandemic. Recent experimentation indicated ORF10 expression moder- ates innate immunity in vitro. However, whether ORF10 af- fects COVID-19 in humans remained unknown. We determine that the ORF10 sequence is identical to the Wuhan-Hu-1 ances-...

COVID-19, the disease caused by SARS-CoV-2, has caused significant morbidity and mortality worldwide. The betacoronavirus continues to evolve with global health implications as we race to learn more to curb its transmission, evolution, and sequelae. The focus of this review, the second of a three-part series, is on the biological effects of the SAR...

Lethal COVID-19 causation most often invokes classic cytokine storm and attendant excessive immune signaling. We re-visit this question using RNA sequencing in nasopharyngeal and 40 autopsy samples from both COVID-19-positive and negative individuals. In nasal swabs, the top 100 genes expressed, and significantly correlated with COVID-19 viral load...

Genomic surveillance and epidemiology have shed light on the viral diversity driving coronavirus disease 2019 (COVID-19) outbreaks and are important during waves of highly transmissible and immune-escaping variants of interest or of concern (VOCs). We analyzed the epidemiological data of the understudied country of Malta and related the patterns ob...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins bind to host mitochondrial proteins, likely inhibiting oxidative phosphorylation (OXPHOS) and stimulating glycolysis. We analyzed mitochondrial gene expression in nasopharyngeal and autopsy tissues from patients with coronavirus disease 2019 (COVID-19). In nasopharyngeal sa...

Biography Dr Stephen Walsh is a clinician scientist with an interest in both rare renal tubular disorders and disorders of blood pressure. His research involves the physiology of epithelial solute transport, and how that relates to blood pressure control, kidney stone formation and renal failure. He collaborates with both NASA and the ESA on the ef...

The role of the space environment in activating a diverse set of genes involved in regulating key cellular pathways is now widely recognized. This includes genes associated with blood control and erythropoiesis, with a particular emphasis on those involved in globin chain production. The comprehensive investigation of haemoglobin biology provides a...

Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney are largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic),...

Bone loss, commonly seen in osteoporosis, is a condition that entails a progressive decline of bone mineral density and microarchitecture, often seen in post-menopausal women. Bone loss has been widely reported in astronauts exposed to a plethora of stressors and in patients with osteoporosis following radiotherapy for cancer. Studies on mechanisms...

Sarcopenia is characterized by loss of muscle mass and strength in the elderly. Interestingly, astronauts suffer from a sarcopenic-like phenotype due to microgravity, thus effective countermeasures and preventive strategies are needed. Earth precision medicine combined with statistical, co-expression network and pathway analysis enables us to explo...

Introduction As humanity continues to push towards interplanetary travel and beyond, short- and long-term adaptation of the human body to extreme environmental conditions in space remains a fundamental concern. An astronaut is subjected to physically and mentally enduring situations like microgravity, extreme heat or cold, radiation, isolation, and...

Space biology research aims to understand fundamental spaceflight effects on organisms, develop foundational knowledge to support deep space exploration and, ultimately, bioengineer spacecraft and habitats to stabilize the ecosystem of plants, crops, microbes, animals and humans for sustained multi-planetary life. To advance these aims, the field l...

Human exploration of deep space will involve missions of substantial distance and duration. To effectively mitigate health hazards, paradigm shifts in astronaut health systems are necessary to enable Earth-independent healthcare, rather than Earth-reliant. Here we present a summary of decadal recommendations from a workshop organized by NASA on art...

Despite surging interest in space travel in recent decades, the impacts of prolonged, elevated exposure to galactic cosmic radiation (GCR) on human health remain poorly understood. This form of ionizing radiation causes significant changes to biological systems including damage to DNA structure by altering epigenetic phenotype with emphasis on DNA...

Human space exploration is hazardous, causing molecular changes that can alter astronauts' health. This can include genomic instability, mitochondrial dysfunction, increased inflammation, homeostatic dysregulation, and epigenomic changes. These alterations are similar to changes during aging on Earth. However, little is known about the link between...

Exercise is a nonpharmacological intervention that improves health during aging and a valuable tool in the diagnostics of aging-related diseases. In muscle, exercise transiently alters mitochondrial functionality and metabolism. Mitochondrial fission and fusion are critical effectors of mitochondrial plasticity, which allows a fine-tuned regulation...

From our previous work we have shown a key miRNA signature that is associated with spaceflight can be used as a biomarker and countermeasure to mitigate the damage caused by space radiation. Here, we have further expanded on this work to determine key biological factors that are being rescued by the countermeasure treatment. We performed RNA-sequen...

Spaceflight poses a unique set of challenges to humans and the hostile spaceflight environment can induce a wide range of increased health risks, including dermatological issues. The biology driving the frequency of skin issues in astronauts is currently not well understood. To address this issue, we used a systems biology approach utilizing NASA’s...

Organismal adaptations to spaceflight have been characterized at the molecular level in model organisms, including Drosophila and C. elegans. Here we extend molecular work to energy metabolism and sex hormone signaling in mice and humans. We found spaceflight-induced changes in insulin and estrogen signaling in rodents and humans. Murine changes we...

MicroRNAs (miRNAs) are small, non-coding RNA molecules that are post-transcriptional regulators of gene expression. miRNAs have been shown to be key regulators of complicated pathological processes and hence great biomarkers for the early prediction of diseases, such as cardiovascular diseases and radiation-associated alteration after spaceflight....

Background: Epidemiological studies have indicated that exposure of the heart to doses of ionizing radiation as low as 0.5 Gy increases the risk of cardiac morbidity and mortality with a latency period of decades. The damaging effects of radiation to myocardial and endothelial structures and functions have been confirmed radiobiologically at high d...

The purpose of the Maleth Program, also known as Project Maleth, is Malta’s first space program to evaluate human skin tissue microbiome changes in type 2 diabetes mellitus (T2DM) patients afflicted with diabetic foot ulcers (DFU). This was carried out in both ground-based models and spaceflight. The first mission (Maleth I) under this program was...

Biological paths of tumor progression are difficult to predict without time-series data. Using median shift and abacus transformation in the analysis of RNA sequencing data sets, natural patient stratifications were found based on their transcriptomic burden (TcB). Using gene-behavior analysis, TcB groups were evaluated further to discover biologic...