Immunometabolism: The Dynamic Interplay of Cytokines and Metabolites

Posted on by Kendra Hanslik

Immunometabolism is the study of how metabolic processes influence immune cell functions and how immune responses, in turn, shape cellular metabolism. This field examines the roles of cytokines and metabolites, which act as signaling molecules and energy sources, respectively. Cytokines can trigger or modulate metabolic pathways in immune cells, affecting their activation, growth, and response capabilities. Similarly, metabolites provide the necessary energy and building blocks that enable immune cells to proliferate, function optimally, and sustain their activity during immune responses. This dynamic interplay is crucial for maintaining health and combating disease. Together, cytokines and metabolites orchestrate a complex network that links metabolic health with immune competence on a systemic and cellular level. This blog discusses how cytokines and metabolites not only influence but also drive immune cell functions, revealing new avenues for therapeutic interventions across a range of diseases.

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From Tracers to Kinetic Selectivity: Highlights from the Target Engagement in Chemical Biology Symposium

Posted on by Anna Bennett

In April 2024, Promega hosted the “Target Engagement in Chemical Biology Symposium” at the Kornberg Center, a research and development hub on Promega’s campus in Madison, Wisconsin. The goal of the symposium was to gather interdisciplinary researchers interested in the field of small molecule target engagement to foster collaboration through knowledge sharing and innovation. The symposium featured a 1.5-day agenda packed with 23 speakers, 4 workshops, poster sessions and social events. Over 130 attendees gathered to participate in the multifaceted event, with participants from different geographic regions and in different research sectors from academia to government to industry.  

People gather in a large atrium with scientific posters and table displays.
Attendees gather for the poster session in Kornberg Atrium. Photo by Anna Bennett (Promega Corporation)

The symposium highlighted the collective commitment to overcoming the challenges in drug discovery by developing more targeted and efficacious treatments, driven by a shared determination to create innovative solutions that address unmet medical needs. While we cannot share all the exciting research presented at the symposium, we are thrilled to highlight a few talks that exemplify the novel work and collaborative spirit of this research community.  

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Rethinking Cell Proliferation Assays

Posted on by Simon Moe

In the field of cancer research, accurately measuring cell proliferation is crucial for assessing the efficacy of therapeutic agents. This is particularly difficult with CDK 4/6 inhibitors, which arrest cells in the G1 phase without stopping their growth. This continued growth can skew results from proliferation assays which rely on factors that naturally scale with cell growth. These include mitochondrial activity (ATP levels), total cell protein, or mRNA as measured through the PRISM molecular barcoding strategy. Even though these cells are not dividing, the increase in these measurements can misleadingly suggest active proliferation.

There is growing awareness among researchers of these challenges.  A recent study highlights these limitations by demonstrating the discrepancies that arise when using metabolic assays to assess cell proliferation after treatment with drugs that induce cell cycle arrest. This blog post delves into the study’s implications and demonstrates how one of Promega’s latest developments is poised to address these challenges.

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Decoding the NAD+/NADH Ratio and Its Crucial Role in Cell Health

Posted on by Kendra Hanslik

Nicotinamide adenine dinucleotide (NAD) exists in two forms in the cell: NAD+ (oxidized) and NADH (reduced). This molecule plays a pivotal role in metabolic processes, serving as a key electron carrier in the redox reactions that drive cellular metabolism. The balance between these two forms, commonly expressed as the NAD+/NADH ratio, is crucial for maintaining cellular function and the intracellular redox state. This article explores the significance of this ratio, how it impacts cellular processes, and the consequences of NAD+/NADH ratio dysregulation.

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What do Exosomes have to do with Cancer Research?

Posted on by Shannon Sindermann
microRNA that is inside exosomes

Discovered in 1983 and initially dismissed as ‘cellular dust,’ exosomes have since emerged as pivotal players in biomedical research due to their roles in intercellular communication, potential as drug delivery vectors and as biomarkers for various diseases. These small extracellular vesicles, measuring 30–150nm, are crucial for transferring proteins, lipids, and nucleic acids — including microRNA (miRNA), mRNA, and non-coding RNA– between cells (1). miRNAs are particularly critical as they regulate gene expression and offer insights into the cellular mechanisms underlying diseases like cancer, enhancing the value of exosomes in cancer research.

Beyond exosomes importance in understanding intracellular communication and organ cross-talk, exosomes can also alter the functions of recipient cells based on their cargo. This capability makes them extremely valuable in providing insights into alterations in cellular communication, tumor microenvironments, metastasis and immune evasion.

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Cancer Moonshot: Solving Tough Problems

Posted on by Michele Arduengo

At the American Association for Cancer Research meeting in April 2016, then Vice President of the United States, Joe Biden, revealed the Cancer Moonshot℠ initiative— a program with the goals of accelerating scientific discovery in cancer research, fostering greater collaboration among researchers, and improving the sharing of data (1,2). The Cancer Moonshot is part of the 21st Century Cures Act, which earmarked $1.8 billion for cancer-related initiatives over 7 years.  The National Cancer Institute (NCI) and the Cancer Moonshot program have supported over 70 programs and consortia, and more than 250 research projects.  According to the NCI, the initiative from 2017 to 2021 resulted in over 2,000 publications, 49 clinical trials and more than 30 patent filings. Additionally, the launch of trials.cancer.gov has made information about all cancer research trials accessible to anyone who needs it (3).

“We will build a future where the word ‘cancer’ loses its power.”

First Lady, Dr. Jill Biden

In February 2022, the Biden White House announced a plan to “supercharge the Cancer Moonshot as an essential effort of the Biden-Harris administration” (4).  Biden noted in his address that, in the 25 years following the Nixon administration’s enactment of the National Cancer Act in 1971, significant strides were made in understanding cancer. It is now recognized not as a single disease, but as a collection comprising over 200 distinct diseases. This period also saw the development of new therapies and enhancements in diagnosis. However, despite a reduction in the cancer death rate by more than 25% over the past 25 years, cancer continues to be the second leading cause of death in the United States [4].

The Cancer Moonshot is a holistic attempt to improve access to information, support and patient experiences, while fostering the development of new therapeutics and research approaches to studying cancer. In this article, we will focus on research, diagnostics and drug discovery developments.

Solving for Undruggable Targets

KRAS , a member of the RAS family, has long been described as “undruggable” in large part because it is a small protein with a smooth surface that does not present many places for small molecule drugs to bind. The KRAS protein acts like an off/on switch depending upon whether it has GDP or GTP bound.  KRAS mutations are associated with many cancers including colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic ductal adenocarcinoma (PDAC). The G12 position in the protein is the most commonly mutated; G12C accounts for 13% of the mutations at this site, and is the predominant substitution found in NSCLC, while G12D is prevalent in PDAC (5).

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Our Maxwell® Travels from Spain to Antarctica to Help Stop the Avian Flu Virus

Posted on by Promega

In January 2024, Antonio Alcamí and Ángela Vázquez, virologists from the Severo Ochoa Centre for Molecular Biology, landed in Antarctica to study the avian flu virus. They embarked on a journey to monitor 17,000 penguins as part of their efforts to study the virus and prevent its spread. Our Maxwell® RSC 48 was delivered to extract nucleic acids from the samples, which are set to be analyzed using qPCR.

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Measles and Immunosuppression—When Getting Well Means You Can Still Get Sick

Posted on by Kelly Grooms
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In 2000 measles was officially declared eliminated in the United States (1), meaning there had been no disease transmission for over 12 months. Unfortunately it was not gone for good. So far in 2024 there have been 8 outbreaks and 131 cases. Ninety of these case (69%) are associated with an outbreak and seventy (53%) have resulted in hospitalization (as of May 2, 2024; 2).  

Help in Limiting a Dangerous Childhood Disease

Before the development of a vaccine in the 1960s, measles was practically a childhood rite of passage. This common childhood disease is not without teeth however. One out of every 20 children with measles develops pneumonia, 1 out of every 1,000 develops encephalitis (swelling of the brain), and 1 to 3 of every 1,000 dies from respiratory and neurological complications (3). Between the years of 1958 and 1962, the US averaged 503,282 reported cases of measles (4). The first measles vaccine was licensed in the U.S. by John Enders in 1963, and not surprisingly, after the measles vaccine became widely used, the number of cases of measles plummeted. By 1970, there were under 1,000 cases (2).

Decreased Childhood Mortality from Other Infectious Diseases—An Unexpected Benefit

What was surprising was that with the disappearance of this childhood disease, the number of childhood deaths from all infectious diseases dropped dramatically. As vaccination programs were instituted in England and parts of Europe, the same phenomenon was observed. Reduction or elimination of measles-related illness and death alone can’t explain the size of the decrease in childhood mortality. Although measles infection is associated with suppression of the immune system that will make the host vulnerable to other infections, these side effects were assumed to be short lived. In reality, the drop in mortality from infectious diseases following vaccination for measles lasted for years, not months (5).

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Embracing Spring at Promega: A Commitment to Environmental Stewardship and Sustainable Growth 

Posted on by Promega

This blog is guest-written by Jason Hankes, Manager, Land & Natural Resources, Promega Corporation 

At Promega, the arrival of spring is not merely a celebration of nature’s rejuvenation, but also a reflection of our steadfast commitment to environmental stewardship. This vibrant season allows us to spotlight a crucial ecological initiative: the controlled prairie burn. Conducted every three to five years across over 25 acres of native prairie restorations, these burns are essential for habitat health. They not only reduce the risk of wildfires but also curb invasive weeds and stimulate new growth. Undertaking these burns exemplifies how Promega reinforces its commitment to environmental stewardship – a foundational principle that guides our operations and influences our architectural designs. 

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Beyond April: Sustaining Momentum in Sexual Assault Awareness and Action  

Posted on by Promega

This guest blog post is written by Tara Luther, Sr. Marketing Specialist, Genetic Identity at Promega.

April 2024 marked the 23rd anniversary of Sexual Assault Awareness Month (SAAM) in the United States. While we have crossed into May, the importance of what SAAM stands for does not diminish with the changing of the calendar. The National Sexual Violence Resource Center (NSVRC) emphasizes that SAAM is a time to not only draw attention to the prevalence of sexual assault, but to also educate individuals and communities about how to prevent sexual violence. 

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