<h4>Researchers will analyze materials from six disease study sites across US</h4>
Multi-omics is a research approach that leverages the power of several different “omics” data types at once to build a detailed picture of factors that contribute to human health and disease.
The National Institutes of Health (NIH) is channeling $50.3 million over the next five years into a new consortium dedicated to advancing the generation and analysis of multi-omics data for human health research. As part of this team, Washington University in St. Louis is establishing and will lead a central production center that functions as a hub for multi-omics analyses for materials from consortium members at each of six disease study sites identified by the NIH.
<a href="https://chemistry.wustl.edu/people/gary-patti?&amp;_ga=2.245277708.866671225.1710415924-433581621.1709556186">Gary Patti</a>, the Michael and Tana Powell Professor of Chemistry in Arts &amp; Sciences and a professor of medicine and of genetics at the School of Medicine, and <a href="https://genome.wustl.edu/people/ting-wang/?_ga=2.245277708.866671225.1710415924-433581621.1709556186">Ting Wang</a>, head of the Department of Genetics at the School of Medicine and the Sanford C. and Karen P. Loewentheil Distinguished Professor of Medicine, are principal investigators with the new consortium. Patti, who recently founded a multi-omics company called <a href="https://panomebio.com/">Panome Bio</a>, is an innovator in multi-omics research, and Wang is involved in multiple other NIH consortia, such as the <a href="https://medicine.wustl.edu/news/nih-funds-centers-to-improve-diversify-reference-human-genome/?_ga=2.20933809.866671225.1710415924-433581621.1709556186">Human Pangenome Reference Consortium</a>.
<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Washington_University_in_St_Louis_Wash_U_leads_new_multi_omics_production_center_for_NIH_research_consortium_Patti_fa8e4a9e2a/Washington-University-in-St.-Louis-WashU-leads-new-multi-omics-production-center-for-NIH-research-consortium-Patti.jpg" alt="Washington University in St. Louis: WashU leads new multi-omics production center for NIH research consortium: Patti"/>
Collaborators will take advantage of cutting-edge resources at Washington University, such as the <a href="https://research.wustl.edu/core-facilities/center-for-metabolomics-and-isotope-tracing/?_ga=2.243156107.866671225.1710415924-433581621.1709556186">Center for Proteomics, Metabolomics, and Isotope Tracing</a> on the Danforth Campus. The university estimates the value of its portion of the new grant at $19.2 million.
“Most human diseases have complex origins that are influenced by a combination of genetic and environmental components such as diet, physical activity, exposure to pollutants and social determinants,” Patti said. “We are working to understand how disease develops in a person by studying the flow of molecular information at multiple levels of ‘omics’ in parallel.”
“*This consortium model eliminates one important barrier to progress by making it easier to collect multi-omics data from the same sets of samples and developing collaborative teams with the appropriate expertise to harmonize and integrate the results,*” he said.
<h4>A more holistic view</h4>
Multi-omics incorporates several “omics” data types, including genomics, epigenomics, transcriptomics, proteomics and metabolomics. Each of these data types reveals distinct information about different aspects of a biological system, and leveraging all these data types at once is becoming increasingly possible with advances in high-throughput technologies and data science.
The integration of multiple types of data from an individual participant’s biological sample can provide a more holistic view of the molecular factors and cellular processes involved in human health and disease, including untangling genetic and non-genetic factors in health and disease. This approach offers great promise in areas such as defining disease subtypes, identifying biomarkers and discovering drug targets.
<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Washington_University_in_St_Louis_Wash_U_leads_new_multi_omics_production_center_for_NIH_research_consortium_Wang_017d37d6a5/Washington-University-in-St.-Louis-WashU-leads-new-multi-omics-production-center-for-NIH-research-consortium-Wang.jpg" alt="Washington University in St. Louis: WashU leads new multi-omics production center for NIH research consortium: Wang"/>
“*With each additional layer of omics information comes more clues about biology,” Wang said. “I’m really excited about the work we will do in this consortium to integrate genomics, proteomics and metabolomics data. This is the future of systems biology.*”
“*Beyond gaining insights into individual diseases, the primary goal of this consortium is to develop scalable and generalizable multi-omics research strategies as well as methods to analyze these large and complex datasets,” said Joannella Morales, a National Human Genome Research Institute (NHGRI) program director involved in leading the consortium. “We expect these strategies will ultimately be adopted by other research groups, ensuring the consortium’s work will have broad and long-lasting impacts for clinical research.*”
<a href="https://www.nih.gov/news-events/news-releases/nih-awards-503-million-multi-omics-research-human-health-disease">Funding for the consortium</a> will support work at six disease study sites, which will examine conditions such as fatty liver diseases, hepatocellular carcinoma, asthma, chronic kidney disease and preeclampsia, among others.
The sites will enroll research participants, at least 75% of whom will be from ancestral backgrounds underrepresented in genomics research. The sites also will collect data on participants’ environments and social determinants of health to be used in conjunction with the multi-omics data. Combining the multi-omic and environmental data can offer an even more comprehensive view of the factors that contribute to disease risk and outcomes.
Specimens provided by participants will be processed at the omics production center at Washington University, which will use high-throughput molecular assays to generate genomics, epigenomics, transcriptomics, proteomics and metabolomics data that will be analyzed to generate molecular profiles of disease and non-disease states.
A data analysis and coordination center will then incorporate all of these data into large, organized datasets that will be made available to the scientific community for further studies.
“*This is a rare opportunity to bring together a bunch of scientists with highly complementary expertise. I expect it to inspire breakthroughs in leveraging multi-omics approaches to understand disease,*” said <a href="https://chemistry.wustl.edu/people/leah-shriver?_ga=2.10043580.866671225.1710415924-433581621.1709556186">Leah Shriver</a>, a research associate professor of chemistry in Arts &amp; Sciences and a co-investigator on the research team.
“*Multi-omics studies are at the forefront of biomedical research and promise to advance our understanding of disease onset and progression,” said Erin Ramos, deputy director of NHGRI’s Division of Genomic Medicine. “All while potentially providing important clues for treatment design and drug-discovery efforts. This new consortium is an important step in making those advances a reality.*”
The award is funded jointly by NHGRI, the National Cancer Institute and the National Institute of Environmental Health Sciences.

WashU leads new multi-omics production center for NIH research consortium

<h3>Tumors are composed of rapidly multiplying cancer cells. Understanding which biochemical processes fuel their relentless growth can provide hints at therapeutic targets.</h3>
Researchers from Washington University in St. Louis have developed a technology to study tumor growth in another dimension — literally. The scientists established a new method to watch what nutrients are used at which rates spatially throughout a tissue.
By using this multidimensional imaging approach, they identified pathways whose activities are uniquely elevated in brain cancer, offering clues for potential treatment strategies. The study was published May 19 in <a href="https://www.nature.com/articles/s41467-023-38403-x">Nature Communications</a>.
“*We figured out how to infer the rate of biochemical reactions directly from discrete regions of tissue,*” said <a href="https://chemistry.wustl.edu/people/gary-patti">Gary Patti</a>, the Michael and Tana Powell Professor of Chemistry in Arts &amp; Sciences and a professor of medicine at the School of Medicine. Patti, who is also a research member of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, is senior author of the new study.
<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Washington_University_in_St_Louis_Wash_U_leads_new_multi_omics_production_center_for_NIH_research_consortium_Patti_fa8e4a9e2a/Washington-University-in-St.-Louis-WashU-leads-new-multi-omics-production-center-for-NIH-research-consortium-Patti.jpg" alt="Washington University in St. Louis: Patti"/>
Human biology is intrinsically 3D in nature. The emerging field of spatial biology aims to capture this geometry by imaging the locations of genes, proteins and metabolites. The approach reported by Patti and colleagues extends spatial profiling to fluxes, the rates at which molecules are transformed inside of cells.
<blockquote>
<h4>“Other technologies provide what is essentially a roadmap of biochemistry. Our goal was to add in a measurement of how fast traffic is flowing on the different roads.”</h4>
</blockquote>
<blockquote>
Gary J. Patti
</blockquote>
By Patti’s analogy, the new method is akin to the feature in Google Maps that uses green and red colors to indicate the density of cars on a given street.
Using a mouse model of glioblastoma, a deadly form of brain cancer in humans, the researchers created a high-resolution map of the “tumor ecosystem.” This allowed them to tell which molecules were located in what parts of the brain and how quickly those molecules were turning into other things.
The results shed light on how cancer cells in a brain tumor get lipids, a basic component of fat.
Lipids are required to make the outermost covering of a cell, known as a membrane. As cancer cells multiply, they need lipids to encase the new cells. Previous work from Patti had shown that cancer cells prefer to scavenge lipids from their local environments. But that was when cancer cells were cultured in isolation with lipids present in the media.
The new study showed that cancer cells in the brain tend to make, rather than siphon off, the lipids that they need to multiply.
“*The brain is a unique environment. The availability of lipids is more limited than in other tissues where tumors reside,*” Patti explained.
The speed at which some lipids were synthesized was as much as 8-fold higher in brain tumors compared with surrounding healthy tissue. Although the exact magnitude of the increase varied, the pattern was surprisingly consistent in cancer cells throughout the tumor.
“*A single tumor can span multiple different environments. The center might be hypoxic, while the outside is in contact with healthy tissue,” Patti said. “You might have predicted differences between these different regions, but we didn’t observe any patterns like that.*”
This finding is important because knowing that cancer cells within brain tumors rely on the same biochemical pathway to fuel their growth means that scientists could target it to slow or stop disease progression.
“*When a pathway is more active, its flux goes up. That makes it a good candidate for therapeutic intervention,” Patti said. “We are excited about testing whether impairment of fatty acid elongation will be effective in treating mouse models of disease.*”
<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Washington_University_in_St_Louis_Spatial_metabolomics_images_of_a_brain_with_a_tumor_1c10f78195.jpg" alt="Washington University in St. Louis: Spatial metabolomics images of a brain with a tumor. Additional details available in Figure 8 from the technical article, “Using mass spectrometry imaging to map fluxes quantitatively in the tumor ecosystem.” (Image courtesy of Patti lab, Nature Communications)"/>
This study was funded in part by the McDonnell Center for Cellular and Molecular Neurobiology, as well as the National Institutes of Health grants R24 OD024624 and R35 ES2028365.

Cancer cells rev up synthesis, compared with neighbors

<a href="https://chemistry.wustl.edu/people/gary-patti">Gary Patti</a>, the Michael and Tana Powell Professor of Chemistry, has been awarded the <a href="https://www.asms.org/about-asms-awards">Biemann Medal</a> from the American Society for Mass Spectrometry for his “pioneering work” in the field of metabolomics, the study of the compounds involved in metabolism.
The ASMS described Patti’s work as “exemplary of how metabolomics should be applied to study biology.” The society also noted that his techniques have become “gold standards in the field.”
The Biemann Medal recognizes “significant achievement in basic or applied mass spectrometry in the early stages of an academic career.” Patti will receive the medal at the <a href="https://lcms.labrulez.com/events/568">ASMS Annual Conference</a> in June, where he will deliver an award lecture.
At WashU, Patti’s lab uses metabolomic approaches to better understand the biology of cells, especially cancer cells. The lab is also committed to developing new laboratory technologies and software to help process exceptionally large volumes of data.
Patti, also a professor of medicine and genetics in the School of Medicine, is the co-lead investigator of a new <a href="https://lcms.labrulez.com/article/3789">National Institutes of Health project</a> that will channel more than $19 million to WashU. The project will focus on multi-omics, an approach that studies cells at multiple levels, including genomics, epigenomics, proteomics, and metabolomics.
“*Without Klaus Biemann’s seminal contributions to the field of mass spectrometry, none of the work that my laboratory does would be possible,” Patti said. “His vision redefined biochemistry, pharmacology, and medicine. It is an incredible honor to be recognized with this prestigious medal in his name.*”

Patti wins medal from the American Society for Mass Spectrometry

Colorectal cancer rates in adults under age 50 have been increasing in the U.S. and globally. The risk of developing such cancers has been rising with each generation since the 1950s, but scientists have not been able to explain why. Understanding the underlying causes will help design prevention strategies for future generations.
<a href="https://surgery.wustl.edu/people/yin-cao/">Yin Cao, ScD</a>, an associate professor of surgery and of medicine in the <a href="https://publichealthsciences.wustl.edu/">Public Health Sciences Division</a> at Washington University School of Medicine in St. Louis, is leading an international team seeking to understand what is driving the increase in early-onset colorectal cancers globally. Her team will do so with an award of up to $25 million over five years from <a href="https://cancergrandchallenges.org/">Cancer Grand Challenges</a>, a global research funding initiative co-founded by Cancer Research UK and the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). According to the organization, the mission of Cancer Grand Challenges is to unite the world’s brightest minds against cancer’s toughest challenges.
The team is funded by Cancer Research UK, the National Cancer Institute, the Bowelbabe Fund for Cancer Research UK, and Institut National Du Cancer in France, through Cancer Grand Challenges.
“The alarming rise of colorectal cancer in young people around the world demands immediate action,” said Cao, also a research member of <a href="https://siteman.wustl.edu/">Siteman Cancer Center</a>, based at Barnes-Jewish Hospital and Washington University School of Medicine. “We used to think colorectal cancer was a disease of the older population, but in the past two decades, the median age of diagnosis for this cancer in the U.S. dropped from 72 to 66 years. Our team aims to unravel and ultimately reverse the intricate network of causal factors throughout the life course that contribute to early-onset colorectal cancer.”
The award will provide funding for Cao’s research team — named Pathways, Risk Factors and Molecules to Prevent Early-onset Colorectal Tumors (PROSPECT) — to develop disruptive and transdisciplinary approaches to address this challenge. Among 176 international teams that applied, Cao’s team is one of five to receive funding this year through Cancer Grand Challenges. The other funded teams are focused on cancer inequities, solid tumors in children, and T cell receptors.
Cao co-leads the team with Andrew Chan, MD, at Massachusetts General Hospital (MGH). The research team also involves nine interdisciplinary co-investigators across the globe, including <a href="https://chemistry.wustl.edu/people/gary-patti">Gary Patti, PhD</a>, the Michael and Tana Powell Professor of Chemistry at Washington University. Patti, a pioneer of mass spectrometry-based technologies, will lead state-of-the-art molecular and metabolic analyses to identify possible new risk factors.
Cao’s lab has led the field of early-onset colorectal cancer research by uncovering risk factors throughout the life course that may contribute to the cancer’s rising incidence, such as obesity; diabetes; metabolic comorbid conditions such as high blood pressure and high cholesterol; prolonged sitting; poor diet; sugar-sweetened beverages; alcohol drinking patterns; and birth via cesarean delivery. Cao’s team also leads work in early detection and understanding molecular pathways of this cancer.
Building upon this past research, Cao will lead the first consortium dedicated to early-onset colorectal cancer risk factor discovery. The PROSPECT Global Consortium will have support from more than 15 international cohorts and electronic health record-based biobanks from high-, middle- and low-income countries. Her team will examine known risk factors and seek to find new ones. The query will encompass environmental exposures throughout the life course, including lifestyle, genetic, environmental and social factors. The team then will characterize possible causal factors and the cumulative impact of exposures over the life course on colorectal cancer initiation and progression, using animal models.
Cao also will also collaborate with clinicians at Siteman Cancer Center’s <a href="https://siteman.wustl.edu/treatment/cancer-types/colorectal/young-onset-colorectal-cancer-program/">Young Onset Colorectal Cancer Program</a> to collect biospecimens along the continuum of early-onset colorectal cancer development. The researchers will analyze these specimens to characterize the cumulative effects of risk factors for early-onset colorectal cancer on the biochemical and molecular states of tissues.
“An understanding of what causes early-onset cancers is important for the development of interventions based on an individual’s risk so that we can prevent disease and death,” Cao said. “Our goal is to maximally integrate human and mechanistic evidence to develop precision prevention strategies.”
In addition to identifying risk factors and evaluating causal factors, the team also will translate these findings to develop and test prevention strategies, including precision prevention trials and community risk-assessment trials.
“By pushing the boundaries of our individual fields, we hope to move quickly to identify opportunities for preventive interventions that can benefit younger populations,” Cao said. “It’s a joint adventure shared by scientists, providers, patients and the public under a unified goal: shaping a hopeful and healthier future for our younger generations.”

Preventing early-onset colorectal cancers aim of $25 million award

A collaborative effort between <a href="https://lcms.labrulez.com/companies/299">Washington University in St. Louis</a>, Agilent Technologies and the biopharmaceutical company Merck aims to expand research in the field of metabolomics, the comprehensive study of small molecules within a biological system.
<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Washington_University_in_St_Louis_Washington_University_collaborates_with_Agilent_Merck_to_expand_metabolomics_research_Patti_ce14d60fe7.jpg" alt="Washington University in St. Louis: Patti"/>
Using top-of-the-line research instrumentation from Agilent, scientists in the Department of Chemistry in Arts &amp; Sciences will develop new metabolomics workflows of interest to many members of the drug-development community. The partnership also includes salary support for postdoctoral research fellows for the next two years.
“Metabolomics provides a direct readout of biochemical activity. It is ideally suited to study the effect that drugs have on cells and tissues,” said <a href="https://chemistry.wustl.edu/people/gary-patti?_ga=2.230989087.1850045254.1716193436-433581621.1709556186">Gary Patti</a>, the Michael and Tana Powell Professor of Chemistry in Arts &amp; Sciences and professor of medicine at the School of Medicine, who leads the university’s portion of the collaboration.
“With these instruments from Agilent, we are delighted to establish a dedicated training laboratory outfitted with cutting-edge mass spectrometry equipment for metabolomics,” said <a href="https://biology.wustl.edu/people/feng-sheng-hu-0?_ga=2.223236379.1850045254.1716193436-433581621.1709556186">Feng Sheng Hu</a>, the Lucille P. Markey Distinguished Professor and dean of the faculty of Arts &amp; Sciences.
“Trainees will be exposed to computational approaches in metabolomics, mass spectrometry, cell work and animal work, as well as many other biochemical techniques — making them exceptional candidates to pursue careers within the biopharmaceutical industry,” Hu said.* “We are grateful to Agilent and Merck for their support in helping Washington University to develop the pipeline of research experts skilled in scientific discovery within the fields of pharmacokinetics, pharmacodynamics, drug metabolism and metabolomics.”*
<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Washington_University_in_St_Louis_Sean_Garcia_Washington_University_collaborates_with_Agilent_Merck_to_expand_metabolomics_research_esearchers_in_the_Patti_laboratory_with_Patti_center_e5dcad9975.jpg" alt="Washington University in St. Louis/Sean Garcia: Researchers in the Patti laboratory, with Patti center."/>
“We are excited to participate in this collaborative effort. The combination of metabolomics with drug metabolism and pharmacokinetics (DMPK) offers significant potential to accelerate drug development,” said Sudharshana Seshadri, vice president of Agilent’s Mass Spectrometry Division. “We are confident that the Agilent LC/TQ and LC/Q-TOF workflow solutions will deliver deep insights with great accuracy and enable rapid progress for our collaborators.”
“This collaboration will fast-track the training of next-generation bioanalytical scientists at Washington University, incorporating new workflows combining metabolomics with DMPK analysis to define mode of action, off-target effects and stratification of results with metabolic biomarkers,” said Darlene Solomon, senior vice president and chief technology officer at Agilent.
“We are excited to embark on this timely collaboration,” said Dan Rock, associate vice president of pharmacokinetics and drug metabolism at Merck Research Laboratories. “Mass spectrometry and computational advancements have opened the scope of metabolomics to more global exposure-response modeling techniques, which present a truly unique path to accelerating drug discovery.”
<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Washington_University_in_St_Louis_James_Byard_Washington_University_collaborates_with_Agilent_Merck_to_expand_metabolomics_research_Patti_right_consults_with_a_graduate_student_6e4599df13.jpg" alt="Washington University in St. Louis/James Byard: Patti (right) consults with a graduate student outside of his laboratory."/>
Researchers in the Patti laboratory use metabolomics to elucidate novel biochemical mechanisms of disease. Patti himself has made major contributions in the development and application of new metabolomics technologies. He is a previous recipient of an <a href="https://source.wustl.edu/2017/07/patti-receives-2017-agilent-early-career-professor-award/">Agilent Early Career Professor Award</a>.
Metabolomics is transforming the ways in which drugs are discovered and developed. For example, researchers can now use metabolomics to create a full tally of drug metabolites — the individual byproducts created when the body breaks down a drug into different substances — as well as the precursors and products of the reactions that these substances affect. Such work enhances the understanding of how drugs circulate around the body and the chemical mechanisms behind their actions. This knowledge is critical to identifying which drugs can be used to treat which diseases and at what doses to administer them.
The new partnership builds upon Patti’s previous work to <a href="https://pubs.acs.org/doi/abs/10.1021/acs.analchem.9b03811">establish an experimental strategy to find off-target effects by metabolomics</a>.
“Off-target effects occur when you develop a drug to do one thing, but then it also does something else unexpectedly,” Patti said. “Off-target effects can lead to toxicity and are one of the biggest reasons that drugs fail during development. The earlier that off-target effects can be identified, the better. Metabolomics has a lot of potential to help here.”
The three-way collaboration offers an opportunity to integrate the unique expertise and perspectives of academic researchers, instrument manufacturers and scientists from the pharmaceutical industry.
“This will position us to tackle the toughest challenges in drug development by applying the newest metabolomics technologies to a wide range of biological systems that span from cells and animals to human patients,” Patti said.
<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Washington_University_in_St_Louis_Sean_Garcia_Washington_University_collaborates_with_Agilent_Merck_to_expand_metabolomics_research_In_partnership_with_Agilent_and_Merc_e962698db1.jpg" alt="Washington University in St. Louis/Sean Garcia: In partnership with Agilent and Merck, scientists in the Department of Chemistry in Arts &amp; Sciences will develop new metabolomics workflows."/>

Washington University collaborates with Agilent, Merck to expand metabolomics research

For over a century, cancer cell metabolism has been viewed as something of a paradox. New work from researchers at Washington University in St. Louis shows that it might not be such an anomaly after all. The study is published Aug. 15 in <a href="https://www.cell.com/molecular-cell/fulltext/S1097-2765(22)00703-1">Molecular Cell</a>.
<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Washington_University_in_St_Louis_Shutterstock_Sugar_metabolism_is_surprisingly_conventional_in_cancer_Mitochondria_the_cell_s_powerhouses_play_an_active_role_in_most_cancers_726527b95c.jpg" alt="Washington University in St. Louis /Shutterstock: Washington University in St. Louis/Shutterstock: Mitochondria — the cell’s powerhouses — play an active role in most cancers. Research from Washington University in St. Louis shows that cancer cells only waste glucose (sugar) because transport into mitochondria is too slow. The study has implications for targeting sugar metabolism in cancer treatment."/>
Glucose, a common sugar in food, is one of the most important nutrients in the body. Cancer cells tend to consume it at an astounding pace. At first glance, that seems to make good sense because cancer cells have a lot of synthesis to do. After all, as tumors grow rapidly, each cell has to replicate its entire contents.
But here’s the catch. Cancer cells don’t use the glucose very efficiently. Instead of sucking all of the energy they can out of glucose, they release most of it as a waste material.
“To extract the maximum amount of energy from glucose, cells must transport its transformation products into mitochondria,” said Gary Patti, the Michael and Tana Powell Professor of Chemistry in Arts &amp; Sciences and of genetics and of medicine at the School of Medicine. Patti, a member of Siteman Cancer Center at Barnes-Jewish Hospital and the School of Medicine, is senior author of the new study.
“There are certain biochemical rules that metabolism is supposed to follow. It’s been interesting to think about why tumors might be allowed to break them,” Patti said. “However, the findings we report here demonstrate that cancer cells do follow conventional principles.”
<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Washington_University_in_St_Louis_Wash_U_leads_new_multi_omics_production_center_for_NIH_research_consortium_Patti_fa8e4a9e2a/Washington-University-in-St.-Louis-WashU-leads-new-multi-omics-production-center-for-NIH-research-consortium-Patti.jpg" alt="Washington University in St. Louis: Patti."/>
<h4>Overflowing</h4>
Mitochondria are tiny compartments inside cells, often referred to as the cell’s power plants or powerhouses. What goes in and out of them is tightly controlled.
As a bit of backstory, a famous biochemist named Otto Warburg first discovered the wasteful nature of tumors in the 1920s. To explain why more energy isn’t harvested from glucose, he postulated that mitochondria are damaged in cancer cells.
“We now know that this is not true. Mitochondria are functional and, in fact, active in most cancers,” Patti said. But that leaves a persistent and vexing question unanswered: Why do cancer cells metabolize so little of the glucose they consume in mitochondria?
“I think what has been confounding is that there has been this notion that cancer cells prefer not to oxidize glucose in their mitochondria,” Patti said. “Perhaps as a legacy of Warburg’s original thinking or maybe because it happens so extensively, the assumption has often been that cancer cells want to use glucose wastefully.”
<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Washington_University_in_St_Louis_Shutterstock_Sugar_metabolism_is_surprisingly_conventional_in_cancer_c350558047.jpg" alt="Washington University in St. Louis/Shutterstock"/>
“When we restrict the amount of glucose taken up by cancer cells, almost all of it makes its way into mitochondria,” Patti said. “But as glucose consumption is increased, the speed of moving glucose-derived molecules into mitochondria can’t keep up.”
In other words, cancer cells only waste glucose away because transport into mitochondria is too slow.
Imagine a bathtub faucet that is spitting out water faster than the drain can remove it. Eventually, the water overflows onto the floor.
“This is not a radically new metabolic paradigm. Most cells do prefer to oxidize glucose in mitochondria rather than excrete it as waste,” Patti said. “Our data suggest that cancer cells are not an exception. They appear to follow the same biochemical patterns as other cells.”
All sorts of explanations have been offered as to why cancer cells might want to be wasteful with their glucose. However, Patti and his team contend that these rationalizations may be unnecessary. In the end, cancer metabolism may not be as unusual as scientists thought.
Cancer cells really do want to metabolize glucose in their mitochondria, and they do so. Until they can’t.
<h4>Saturated</h4>
The Patti team’s discovery was made possible by a powerful technology called metabolomics.
“During the past decade, advances in the field of metabolomics and mass spectrometry have been extraordinary,” Patti noted. “We have now reached a point where measuring molecules in single cells is even possible.”
In this study, the researchers combined metabolomics with stable isotope tracers. This allowed them to tag different parts of glucose so that they could track it inside of cells, watching the speed at which things entered mitochondria or were excreted from cells. That is how the scientists discovered that the normal pathways for transporting fuel were getting outpaced, or saturated, in cancer cells.
The rate at which tumors consume glucose has been exploited by doctors in the clinic for decades as a way to diagnose cancer and identify its stage. It also has led some to believe that limiting glucose uptake with drugs or by eating a sugar-free diet might “starve” the cancer cells to death.
This study’s findings raise questions about such a strategy.
“We may need to rethink how best to target glucose metabolism in cancer,” Patti said. “If cancer cells take up more glucose than they need, and using it wastefully is not a driver of disease, then glucose metabolism may not be as attractive of a therapeutic target as we had hoped.”
<h6>Funding: Financial support was received for this work from NIH awards R35ES028365 and R24OD024624, as well as the Edward Mallinckrodt Jr. Foundation and the Pew Charitable Trusts.</h6>

Sugar metabolism is surprisingly conventional in cancer

Two teams of engineers led by faculty in the McKelvey School of Engineering at <a href="https://lcms.labrulez.com/companies/299">Washington University in St. Louis</a> will work toward developing products to monitor drinking water quality and to detect explosives with an electronic nose with one-year, $650,000 Convergence Accelerator Phase 1 grants from the National Science Foundation (NSF).
Barani Raman, professor of biomedical engineering, and Daniel Giammar, the Walter E. Browne Professor of Environmental Engineering, will lead teams of researchers from Washington University and other institutions and entities funded under the NSF’s Convergence Accelerator program, designed to address national-scale societal challenges through convergence research and to transition basic research and discovery into practice to solve these challenges aligned with specific research themes. Among the themes are <a href="https://new.nsf.gov/news/nsf-spurs-technology-development-biological">real-world chemical sensing applications</a>, bio-inspired design innovations and <a href="https://new.nsf.gov/news/nsf-invests-9-8m-advance-equitable-water-solutions">equitable water solutions</a>.
Raman and his collaborators have been working for nearly two decades to harness insects’ keen sense of smell into a sensor that could be used to detect explosives and in other applications. Now, they will take it a step further by incorporating artificial intelligence (AI) and nanotechnology to create a sensor, or electronic nose, to detect explosive volatile organic compounds.
Raman, professor of biomedical engineering, will work with longtime McKelvey Engineering collaborators Shantanu Chakrabartty, the Clifford W. Murphy Professor in the Preston M. Green Department of Electrical &amp; Systems Engineering; Srikanth Singamaneni, the Lilyan &amp; E. Lisle Hughes Professor in the Department of Mechanical Engineering &amp; Materials Science; and Braden Giordano, associate superintendent of the Chemistry Division at the U.S. Naval Research Laboratory.
<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Washington_University_in_St_Louis_Water_quality_monitor_locust_inspired_electronic_nose_under_development_cover_image_0bced48a34.jpg" alt="Washington University in St. Louis: Clockwise from top left: Raman, Chakrabartty, Singamaneni, Giordano, Steensma, Parker, Ling, Giammar."/>
Using the information gathered from their research in developing bio-inspired sensors, the team plans to create an AI-enabled, nanoparticle-based electronic nose device that can be used to gather and validate data. This portable proof-of-concept device would merge two ideas: a large, nanostructured chemical sensor array with diverse functions and the sensing and AI principles it has identified in the olfactory system of locusts. With the data, they plan to develop a library of known signatures for various explosive vapors at various concentration ranges. 
In addition to detecting volatile organic compounds, the electronic nose could also be used in biomedicine, homeland security, environmental monitoring, climate change technologies and the flavor and food industry. The team plans to work with industry partners to tailor the design for various uses. 
“A decade ago, we did not yet have the technology to develop a field-deployable and robust electronic nose,” Raman said. “The recent advances in biological olfaction, combined with developments in materials science and electronics for remote and long-term monitoring, helped us to understand the computing principles in biological olfaction. In addition, the vast improvements in AI, machine learning and data science provided a new opportunity to develop a robust artificial chemical sensing system.”
Raman acknowledges that a device equal in capabilities as a biological olfactory system such as the locust’s is a Holy Grail. However, this new work and design plan will consider the key requirements in various applications and develop priorities of capabilities needed in the electronic nose technology.
In the second McKelvey Engineering-led Convergence Accelerator project, Giammar, also the director of the university’s Center for the Environment, will lead a team in developing a drinking water-quality monitoring tool based on point-of-use water filters. The research will focus on residents of disadvantaged communities served by small public water systems and those in urban locations served by large water systems with an aging infrastructure as well as those who source water from private wells with lower monitoring requirements.
The team will evaluate the ability of commercially available point-of-use filters, such as faucet-mounted filters, to monitor copper, zinc, manganese, <a href="https://icpms.labrulez.com/library?search=hexavalent+chromium">hexavalent chromium</a>, arsenic, microorganisms, and per- and polyfluorinated alkyl substances, or <a href="https://lcms.labrulez.com/library?search=PFAS">PFAS</a>, the widely used “forever chemicals” linked with harm to the environment and to human health.
“In urban settings, recent crises with lead found in drinking water in Flint, Michigan, and Newark, New Jersey, highlight the threats to public health posed by aging water supply infrastructure,” Giammar said. “The existing monitoring framework is often not enough to identify degraded water quality for those populations most affected, making this an environmental justice issue as much as a water quality issue.”
Giammar’s team includes co-principal investigators from WashU, including Fangqiong Ling and Kimberly Parker, both assistant professors of energy, environmental &amp; chemical engineering in McKelvey Engineering, and Joe Steensma, professor of practice at the Brown School; as well as researchers from the University of Illinois at Urbana-Champaign, including Steven Wilson, groundwater hydrologist and principal scientist for the Illinois State Water Survey, Thanh Huong Nguyen, the Ivan Racheff Professor of Environmental Engineering in Civil &amp; Environmental Engineering, and John Scott, senior analytical chemist in the Illinois Sustainable Technology Center. 
Giammar’s project also has external partners, including the Midwest Assistance Program, the Rural Community Assistance Partnership, the Water Quality Association, and the U.S. Environmental Protection Agency.

Water quality monitor, locust-inspired electronic nose under development

A new study with zebrafish shows that a deadly form of skin cancer — melanoma — alters the metabolism of healthy tissues elsewhere in the body. The research from Washington University in St. Louis suggests that these other tissues could potentially be targeted to help treat cancer.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Washington_University_in_St_Louis_Cancer_has_ripple_effect_on_distant_tissues_Patti_bca1fbd7a0.jpg" alt="Washington University in St. Louis: Patti." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Washington_University_in_St_Louis_Cancer_has_ripple_effect_on_distant_tissues_Patti_bca1fbd7a0.jpg 228w," sizes="100vw" width="1400" height="959">“Tumors rely on a constant supply of nutrients to grow. Instead of competing with tumors for nutrients, other tissues can reprogram their metabolism to be complementary. In some instances, this may even allow healthy tissues to feed the tumor,” said <a target="_blank" rel="noopener noreferrer" href="https://chemistry.wustl.edu/people/gary-patti">Gary Patti</a>, the Michael and Tana Powell Professor of Chemistry in Arts &amp; Sciences at Washington University and a professor of chemistry and medicine at the School of Medicine.Patti is the corresponding author of the study published May 13 in <a target="_blank" rel="noopener noreferrer" href="https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00180-7">Cell Metabolism</a>.Cancer consumes tremendous amounts of glucose, a key source of energy for cells in the body. Glucose, or blood sugar, is derived from food and transported around the body through the bloodstream after eating. Tumors actively soak up glucose as a fuel to support their rapid growth.This trait is so well known that physicians regularly use it as a diagnostic test for cancer, where patients are administered a specific form of glucose that can be monitored with a PET scan. What is less clear is how a tumor’s penchant for glucose affects other tissues.“Glucose levels are tightly regulated,” Patti said. “When glucose levels get too low, it’s dangerous. We wanted to know whether a tumor with a high avidity for glucose might influence glucose levels in the blood.”Even when healthy people go a long period of time without eating, blood glucose levels are kept relatively constant. That is because glucose can be made by the liver when it cannot be obtained directly from food.“As it turns out, the liver counters the impact of the tumor by synthesizing glucose,” Patti said. “It’s very similar to what occurs during a fast.”<blockquote><h5>What is metabolic crosstalk?</h5><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Washington_University_in_St_Louis_Cancer_has_ripple_effect_on_distant_tissues_afa2b13b9e.jpg" alt="Washington University in St. Louis: Cancer has ripple effect on distant tissues." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Washington_University_in_St_Louis_Cancer_has_ripple_effect_on_distant_tissues_afa2b13b9e.jpg 214w," sizes="100vw" width="1125" height="820"><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/articles?search=Gary+Patti">Gary Patti</a> is an expert in the field of <a target="_blank" rel="noopener noreferrer" href="https://source.washu.edu/2018/10/metabolomics-for-the-masses/">metabolomics</a>, the comprehensive study of small molecules within a biological system.“In metabolic crosstalk, two tissues within one biological system exchange molecules,” Patti explained.“One tissue takes up a metabolite and transforms it into a different molecule that is released. The released molecule is then taken up by another tissue,” Patti said. “Imagine that happening a bunch of times with metabolites flowing in bidirectional ways between various pairs of tissues.”</blockquote>Working with zebrafish, Patti and co-authors including other researchers at the School of Medicine developed a new approach to study melanoma’s impact on different tissues in the body that uses a technology called metabolomics.The scientists fed the zebrafish special versions of nutrients tagged with isotope labels. These labels allowed the scientists to track where nutrients go and into what molecules they get broken down. They found that a molecule being spit out by the tumor was being taken up by the liver to make glucose.By applying metabolomics to individual zebrafish, the scientists observed that melanoma tissues in the body consume about 15 times more glucose than the other tissues they measured. Despite this burden, the zebrafish were able to maintain circulating glucose levels, apparently by making glucose in the liver through a process that is ordinarily triggered when we go without eating.But it was clear that otherwise healthy tissues were affected in many ways by the presence of melanoma.The scientists examined tissues in the liver, intestine, fin, muscle, brain, blood, and eye of the zebrafish. They observed metabolic dysregulation across most of the tissues — indicating that melanoma broadly impacts whole-body metabolism.“There is clear metabolic crosstalk between melanoma and other tissues,” Patti said. “The metabolic relationship between melanoma and liver is partly characterized by a gene called BCAT1 in the cancer cells. BCAT1 goes from essentially being turned off in healthy skin cells to being highly expressed in zebrafish melanoma. By looking at melanoma from human patients, we were able to confirm that the same pattern holds in people.”Much of the previous research on cancer has focused on the metabolism of the tumor itself.“Our work shows that a lot of interesting metabolic changes are also occurring beyond the tumor,” Patti said. “We have demonstrated that, at least in some cases, these metabolic changes in non-malignant tissues occur to support the tumor. This is exciting because it means that we might be able to target the metabolism of healthy tissues as a potential treatment for cancer.”<blockquote>A special note: The authors of this paper dedicated their work to the late Stephen L. Johnson, who was an inspiring mentor to them. His collaborative generosity was essential to carrying out these studies. Read more about Johnson on the School of Medicine <a target="_blank" rel="noopener noreferrer" href="https://medicine.wustl.edu/news/obituary-stephen-l-johnson-professor-genetics-56">website</a>.</blockquote>Financial support was received for this work from National Institutes of Health awards R35ES028365, U01CA235482, and R24OD024624, as well as the Edward Mallinckrodt, Jr. Foundation and the Pew Charitable Trusts.

Cancer has ripple effect on distant tissues

Batteries have become so integral to everyday life – powering everything from mobile devices to electric vehicles and renewable energy storage systems – that people often don’t even think about them. But our increasing reliance on batteries has made considerations like their sustainability and ability to hold charge in a range of environments and the ability to reliably source materials needed to produce them urgent considerations.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Washington_University_in_St_Louis_Peng_Bai_Rajeev_Gopal_and_Ethan_Boutelle_Beyond_lithium_Sodium_based_batteries_may_power_the_future_Peng_Bai_s_research_group_combines_stable_536989e74c.jpg" alt="Washington University in St. Louis / Peng Bai, Rajeev Gopal and Ethan Boutelle: Peng Bai’s research group combines stable sodium metal plated in liquid electrolyte (left) with precisely engineered particles of sodium vanadium phosphate (right) to create safe and efficient sodium batteries." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Washington_University_in_St_Louis_Peng_Bai_Rajeev_Gopal_and_Ethan_Boutelle_Beyond_lithium_Sodium_based_batteries_may_power_the_future_Peng_Bai_s_research_group_combines_stable_536989e74c.jpg 234w," sizes="100vw" width="1200" height="800"><a target="_blank" rel="noopener noreferrer" href="https://engineering.washu.edu/faculty/Peng-Bai.html">Peng Bai</a>, associate professor of energy, environmental &amp; chemical engineering in the McKelvey School of Engineering at Washington University in St. Louis, received a two-year, $550,000 Partnerships for Innovation – Technology Translation award from the National Science Foundation to support his work on sodium-based batteries. The award will allow Bai to expand his prior NSF-funded research to scale up and commercialize his sodium battery technology.&nbsp;Bai’s sodium-based batteries deliberately move away from lithium and other rare elements used in traditional batteries. Sodium, a more abundant and easier to process material, promises lower production costs and alleviated supply chain vulnerabilities, fostering a more sustainable and economically efficient energy landscape. Sodium-based batteries may also offer enhanced fast-charging capabilities and improved operation in cold environments, expanding their potential application in large-scale energy storage and portable electronics, including electric vehicles.The project, “<a target="_blank" rel="noopener noreferrer" href="https://www.nsf.gov/awardsearch/showAward?AWD_ID=2431923">Development of high-performance long-life electrodes for sustainable sodium-based batteries</a>,” has three main goals: ensuring consistency in larger production batches, developing greener manufacturing processes using water instead of toxic solvents, and optimizing production processes at a commercial scale. These advancements would pave the way for sodium-based batteries to make their way into everyday technologies within five years, Bai says.

Beyond lithium: Sodium-based batteries may power the future

Amyloid-beta (A-beta) aggregates are tangles of proteins most notably associated with neurodegenerative diseases such as Alzheimer’s. Despite its constant stint in the limelight, however, researchers have been unable to get a good understanding of how A-beta comes together and breaks apart.“The way A-beta behaves in a variety of environments, including the human brain, is elusive,” said Brian Sun, an electrical systems and engineering alumnus of&nbsp;Washington University in St. Louis who is now an MD/PhD student at the School of Medicine.“There’s an understanding of growth and decay that isn’t fully fleshed out,” he added.That’s going to change, thanks to research recently <a target="_blank" rel="noopener noreferrer" href="https://pubs.acs.org/doi/10.1021/acs.nanolett.4c01263">published</a> by Sun with colleagues in <a target="_blank" rel="noopener noreferrer" href="https://engineering.wustl.edu/faculty/Matthew-Lew.html">Matthew Lew’s lab</a> in the Preston M. Green Department of Electrical &amp; Systems Engineering at WashU’s McKelvey School of Engineering.In first-of-its-kind work, Sun and colleagues were able to measure amyloid fibril beta-sheet assemblies, the underlying girders of the protein conglomeration, while they were changing. Previous high-resolution microscopy studies have only gotten static shots.“We wanted to look specifically at dynamics of the underlying structure of A-beta that could be responsible for the changes we’re seeing, not just changes in the overall shape,” said Sun, the paper’s first author.Lew used Lego bricks in an analogy, noting that current imaging technology shows you the full Lego building but not a look at how individual bricks are organized.“The individual proteins are always changing in response to their environment,” said Lew, an associate professor. “It is like having certain Lego bricks causing other bricks to change their shape. The changing architecture of the proteins and the assembled aggregates together leads to the complexity of neurodegenerative disease.”The Lew lab has developed a new type of imaging tech that allows researchers to see the orientation and other minute details in nanostructures of biological systems that were previously invisible. Their technique — single-molecule orientation–localization microscopy (SMOLM) — uses flashes of light from chemical probes to visualize the sheets of peptides underlying Aβ42, one kind of A-beta peptide.Using SMOLM lets them look at individual orientation of the underlying beta-sheets to see the relationship between their organization and how that relates to the amyloid protein’s overall structure.<h4>Multiple ways to remodel</h4>Aβ42 is constantly changing, and step one is to try to find a method to the madness, a model or pattern of action to predict the protein’s behavior.Now that the Lew lab can make these measurements, they made some intuitive observations and found some surprises hidden in the amyloid-beta architecture.As expected, stable Aβ42 structures tend to retain stable underlying beta-sheets; growing structures have underlying beta-sheets that become more defined and rigid as the growth continues. Decaying structures exhibit increasingly disordered and less rigid beta-sheets. But they also found more than one way that Aβ42 can renovate.“There are multiple different ways for Aβ42 structures to remain stable, or grow and decay,” Sun said.The researchers also discovered that Aβ42 can grow and decay in ways that defy expectations. For example, Aβ42 can grow and decay in ways that preserve the underlying structure; sometimes there’s growth where the peptides just pile on, but the underlying beta-sheet orientations don’t change. In other cases, Aβ42 undergoes “stable decay,” where the opposite happens, i.e. peptides leave, but beta-sheet structure remains.&nbsp; Finally, Aβ42’s beta-sheets sometimes reorganize and change orientations without immediate accompanying changes to the overall shape. These nano-structural reorganizations can predispose to future large-scale remodeling.“Because SMOLM can track Aβ42’s underlying organization and not just its shape, we can see different kinds of subtypes of remodeling that aren’t visible to diffraction-limited, non-orientation imaging modalities,” Sun said.If it all sounds a bit vague, keep in mind this is the first pass at even looking at these constantly shifting nanoscale structures. It’s all the more notable that Sun crafted this work while juggling COVID-19 lockdown restrictions and his undergraduate course load at WashU, which he completed in three years. It paves the way for him and others to really get a handle on amyloid architecture.During the graduate phase of his MD/PhD training, Sun plans to design nanoscale imaging systems and sensors that could reveal the hidden mechanisms of difficult-to-treat diseases.Sun credits McKelvey Engineering and the Lew lab for the rigorous training that made this study and academic trajectory possible, as well as the MSTP for supporting his continued research post-graduation. “I’m really glad I went through this journey,” he said.

WashU researchers shine light on amyloid architecture

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