Category Archives: Cell Biology

Cell Biology

SGIOY: 3 Biotech Stocks With Potential Future Gains – StockNews.com

The pharmaceutical industry has grown substantially in recent years, and the rising demand and tech integration make its outlook promising. Moreover, the industrys ability to maintain stability despite economic uncertainties makes it an attractive investment destination.

Given the favorable industry backdrop, investors could consider buying quality pharma stocks Shionogi & Co., Ltd. (SGIOY), Exelixis, Inc. (EXEL), and Jazz Pharmaceuticals plc (JAZZ) to beat the market.

The pharmaceutical market is experiencing robust growth driven by innovative drugs and increased healthcare demand, especially in emerging markets. Original prescription drugs dominate the market, with a few blockbuster drugs generating over $1 billion in revenue annually.

The industrys growth is also propelled by innovations like cell and gene therapy, mRNA vaccine technology, improving supply chains, and evolving product offerings. As per Statista, the global pharmaceutical market revenue is projected to reach $1.16 trillion this year.

Additionally, progress in the field of cancer biology and the increasing prevalence of severe diseases make precision medicine indispensable. Moreover, ongoing technological advancements and breakthroughs in cell biology continue to drive the market forward.

The Precision Medicine market is expected to grow from $77.02 billion this year to $99.24 billion by 2028, registering a CAGR of 5.2%.

Furthermore, the pharmaceutical industry increasingly embraces artificial intelligence (AI). Strategic investments in AI partnerships are growing, underlining the importance of AI in pharmaceutical advancements. The pharmaceutical industry is also experiencing growth in generative AI for drug discovery, driven by the availability of extensive datasets and collaborative efforts.

The global generative AI in drug discovery market size is projected to surpass around $1.13 billion by 2032, expanding at a CAGR of 27.1%.

Considering these conducive trends, lets analyze the fundamentals of three Biotech picks, beginning with the third choice.

Stock #3: Shionogi & Co., Ltd. (SGIOY)

Headquartered in Osaka, Japan, SGIOY engages in the research, development, manufacture, and distribution of pharmaceuticals, diagnostic reagents, and medical devices. The companys offerings include Fetroja, a multidrug-resistant bacterial infection treatment; Xofluza, an influenza virus drug; and Tivicay, an anti-HIV drug.

On October 12, 2023, SGIOY presented real-world evidence (RWE) at IDWeek2023, suggesting that the use of Fetroja (cefiderocol) effectively treats Gram-negative infections, particularly in patients who received it earlier (within 6-20 days of diagnosis), resulting in lower in-hospital all-cause mortality (IHACM).

The study highlights the clinical utility of Fetroja in the treatment of challenging Gram-negative infections, addressing a significant health concern related to antimicrobial resistance.

On October 6, SGIOY acquired 1,129,800 shares of its common stock, valued at 7.42 billion ($49.56 million) between September 1, 2023, and September 30, 2023. This acquisition aligns with the boards resolution on July 31, 2023, to acquire up to 12,500,000 shares with a maximum cost of 75 billion ($501.29 million) from August 1, 2023, to March 31, 2024. As of September 30, 2023, SGIOY had acquired 3,052,200 shares valued at 19.43 billion ($129.88 million).

SGIOYs revenue grew 52.2% year-over-year to 109.31 billion ($730.62 million) in the fiscal first quarter that ended June 30, 2023. The companys operating profit rose 274.9% year-over-year to 46.59 billion ($311.40 million).

In addition, profit attributable to owners of the parent rose 22.6% from the prior years quarter to 42.56 billion ($286.61 million), and EPS amounted to 144.57 billion, up 25.6% year-over-year.

SGIOYs revenue for the current fiscal year ending March 2024 is likely to rise 5.3% year-over-year to $2.90 billion. Its EPS is expected to be $0.94 in the same year. Also, it has surpassed the consensus revenue estimates in each of the trailing four quarters, which is remarkable.

The stock has gained 7% over the past three months to close the last trading session at $11.23.

SGIOYs POWR Ratings reflect this promising outlook. The stock has an overall rating of B, equating to a Buy in our proprietary rating system. The POWR Ratings are calculated by considering 118 different factors, with each factor weighted to an optimal degree.

SGIOY has a B for Growth, Value, and Quality. It is ranked #15 in the 359-stock Biotech industry.

In addition to the highlighted POWR Ratings, one can see SGIOYs ratings for Stability, Momentum, and Sentiment here.

Stock #2: Exelixis, Inc. (EXEL)

EXEL explores, develops, and markets novel cancer treatments. The company provides CABOMETYX tablets for advanced renal cell carcinoma patients with previous anti-angiogenic therapy and COMETRIQ capsules for progressive and metastatic medullary thyroid cancer treatment.

On September 12, EXEL and Insilico Medicine, a global clinical-stage biotechnology company powered by generative AI, unveiled an exclusive license agreement, granting EXEL global rights to develop and commercialize ISM3091, a potentially best-in-class small molecule inhibitor of USP1, which has emerged as a synthetic lethal target in the context of BRCA-mutated tumors.

The partnership leverages EXELs clinical development expertise and highlights ISM3091s potential in addressing various BRCA-mutant tumors, including those found in ovarian, prostate, and breast cancer.

On August 24, the Alliance for Clinical Trials in Oncologys independent Data and Safety Monitoring Board (DSMB) unanimously recommended prematurely concluding the phase 3 CABINET pivotal trial due to an exceptional surge in efficacy observed at an interim analysis.

This outcome positions EXEL as an oncology innovator, particularly in addressing advanced pancreatic or extra-pancreatic neuroendocrine tumors where no established standard of care exists post-therapy.

In the second quarter that ended June 30, 2023, EXELs total revenues increased 12% year-over-year to $469.85 million. Its income before income taxes rose 13.4% from the year-ago quarter to $100.39 million. The companys non-GAAP net income and non-GAAP net income per share stood at $100.30 million and $0.31, up 11.8% and 10.7% year-over-year, respectively.

EXEL reaffirms its fiscal year 2023 financial guidance, with expectations of total revenues between $1.78 billion and $1.88 billion. Net product revenues are estimated to fall within the range of $1.58 billion to $1.68 billion, while the cost of goods sold is projected to be 4.0% to 5.0% of net product revenues.

Analysts expect EXELs revenue to increase 14.7% year-over-year to $472.33 million in the fiscal third quarter that ended September 2023. The companys EPS for the to-be-announced quarter is expected to be $0.18. Moreover, EXEL exceeded the consensus revenue and EPS estimates in three of the four trailing quarters.

The stock has gained 36.4% over the past year and 10.4% over the past three months, closing the last trading session at $21.36.

EXELs robust prospects are reflected in its POWR Ratings. The stock has an overall rating of B, which translates to a Buy in our proprietary rating system.

EXEL has an A grade for Value and Quality and a B for Sentiment. It is ranked #11 in the same industry. Click here to access EXELs additional ratings for Growth, Momentum, and Stability.

Stock #1: Jazz Pharmaceuticals plc (JAZZ)

JAZZ identifies, develops, and commercializes pharmaceutical products for unmet medical needs in the United States, Europe, and internationally. The company has a portfolio of products and product candidates focusing on neuroscience, including sleep medicine and movement disorders, and oncology, such as hematologic and solid tumors.

On September 21, JAZZ announced that the European Commission had granted marketing authorization for Enrylaze (JZP458), a recombinant Erwinia asparaginase, for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in patients who are hypersensitive or have silent inactivation to E. coli-derived asparaginase.

Enrylaze, known as Rylaze in the United States and Canada, is a new Erwinia-derived asparaginase with a safe profile. This approval is significant in ensuring patients can complete their asparaginase treatment regimen for improved outcomes in ALL and LBL.

On August 2, JAZZ announced that it had entered into a Letter of Intent (LOI) with the Pan-Canadian Pharmaceutical Alliance (pCPA) for Rylaze in Canada.

During the fiscal second quarter that ended June 30, 2023, JAZZs total revenues increased 2.6% year-over-year to $957.32 million. Its income from operations rose 84.3% year-over-year to $157.64 million, and non-GAAP net income rose 6.4% year-over-year to $325.13 million.

Moreover, its adjusted earnings per share increased 4.9% from the year-ago quarter to $4.51.

JAZZ anticipates strong performance across key metrics in its non-GAAP financial guidance for 2023. The company expects a gross margin of 93% and SG&A expenses in the range of $1.05 billion to $1.11 billion, representing 27% to 30% of total revenues. Research and development (R&D) expenses are projected to be between $675 million and $725 million, comprising 17% to 19% of total revenues.

Additionally, the company had projected a net income of $1.29 billion to $1.34 billion, resulting in a net income per diluted share between $18.15 and $19.00.

Street expects JAZZs revenue for the quarter that ended September 2023 to increase 3.1% year-over-year to $970.04 million. Its EPS for the same quarter is likely to amount to $4.90.

Shares of JAZZ rose marginally intraday to close the last trading session at $129.12.

Unsurprisingly, JAZZ has an overall rating of A, which translates to a Strong Buy in our proprietary rating system.

It has an A grade for Value and a B for Growth and Quality. It is ranked #3 in the same industry. Click here to access JAZZs Momentum, Stability, and Sentiment ratings.

What To Do Next?

Get your hands on this special report with 3 low priced companies with tremendous upside potential even in todays volatile markets:

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SGIOY shares were trading at $11.40 per share on Monday morning, up $0.17 (+1.51%). Year-to-date, SGIOY has declined -7.92%, versus a 14.99% rise in the benchmark S&P 500 index during the same period.

Her interest in risky instruments and passion for writing made Kritika an analyst and financial journalist. She earned her bachelor's degree in commerce and is currently pursuing the CFA program. With her fundamental approach, she aims to help investors identify untapped investment opportunities. More...

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SGIOY: 3 Biotech Stocks With Potential Future Gains - StockNews.com

Cell Biology

Association for Molecular Pathology Publishes Best Practice … – Technology Networks

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The Association for Molecular Pathology (AMP), the premier global molecular diagnostic professional society, has published a set of 13 best practice recommendations for validating and reporting clinical circulating tumor DNA (ctDNA) or liquid biopsy assays and their related scientific publications. The manuscript, Recommendations for Cell-free DNA Assay Validations: A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists (CAP), was released online ahead of publication in The Journal of Molecular Diagnostics.

One of the most important technological advances in molecular diagnostics over the past decade has been the ability to accurately detect and measure low abundance ctDNA in blood and body fluids, said Christina Lockwood, PhD, Chair of the AMP Liquid Biopsy Working Group and Professor and Division Head of Laboratory Genetics at the University of Washington School of Medicine. As with any emerging technology or methodology, the way these liquid biopsy assays are developed, validated, and reported can vary. This new report provides a set of evidence-based recommendations that can help promote standardization, transparency, and quality improvement among laboratories.

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The AMP Clinical Practice Committees Liquid Biopsy Working Group, including organizational representation from the American Society of Clinical Oncology (ASCO) and CAP, developed a set of recommendations for validating, reporting, and publishing clinical ctDNA assays. The recommendations are based on a review of more than 1,200 publications that describe ctDNA assay performance in patients with lymphoma and solid tumor malignancies and subject matter expert professional experience. The recommendations include reporting key pre-analytical considerations and assay performance metrics.

This new report was meant to summarize the current collective state of knowledge and assist clinical laboratory professionals with liquid biopsy assay validation, said Susan Hsiao, MD, PhD, 2023 AMP Clinical Practice Committee Chair and Associate Professor of Pathology and Cell Biology at Columbia University Irving Medical Center. As part of our ongoing commitment to improving clinical practice and patient care, AMP will continue to reassess and modify our recommendations as these technologies become more sensitive and additional trials are available to evaluate assay performance and clinical utility.

Reference: Lockwood CM, Borsu L, Cankovic M, et al. Recommendations for cell-free DNA assay validations. J Mol Diag. Published online October 2023:S1525157823002192. doi: 10.1016/j.jmoldx.2023.09.004

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Association for Molecular Pathology Publishes Best Practice ... - Technology Networks

Cell Biology

A new cell type with links to gastric cancer steps up for its mugshot – Fred Hutch News Service

Deep inside the stomachs of an estimated half of the worlds population lurks a bacterium known as Helicobacter pylori, a bug that means business. While many people are infected and never even know, in some cases chronic H. pylori infections predispose individuals to develop gastric (stomach) cancer, the fifth most common cancer type worldwide. The Salama Lab in the Human Biology Division at Fred Hutchinson Cancer Center has built its reputation studying this enigmatic bug, focusing on the bacterium, the host, and everything in between. A recent study from the labpublished in Cancer Research Communications and helmed by former postdoc Dr. Valerie OBrientakes the team into uncharted territory and promises a greater understanding of how H. pylori promotes gastric disease.

In order to understand the relationship between H. pylori and gastric cancer, explains Dr. Salama, its important to distinguish between the tissue inflammation that H. pylori causes and the development of gastric cancer. Indeed, the link between inflammation and carcinogenesis in the stomach is complicatedinflammation isnt strictly required for gastric cancer to develop, and many patients with stomach inflammation wont develop gastric cancer. To better clarify this relationship, Drs. OBrien and Salama turned to an innovative transgenic mouse model in which an oncogenic KRAS protein is artificially expressed the stomachs chief cells (the cells which produce and secrete digestive enzymes), which causes gastric dysplasia similar to what is seen in human patients prior to the development of gastric cancer. In what was a surprising finding, the team discovered that H. pylori-driven inflammation synergizes with oncogenic KRAS to worsen gastric dysplasia in these mice. This suggested that H. pylori may not merely plant the seeds of gastric cancer, but may also provide fertile ground for those seeds to grow. However, one big question remained: was H. pylori simply accelerating disease progression in these mice, or was it causing a different disease trajectory altogether?

In their most recent publication, Dr. OBrien and colleagues address this question by leveraging state-of-the-art single cell RNA sequencing (scRNA-seq) of stomach tissue from KRAS-expressing mice with or without concurrent H. pylori infection. By clustering cell types based on the expression of different marker genes and comparing these cell types between conditions, the team found that the combination of oncogenic KRAS expression and H. pylori infection resulted in the expansion of a specific type of pit cell (a different cell type found in the stomach lining) expressing a gene called Muc4. Importantly, they found very few Muc4-expressing pit cells in mice with oncogenic KRAS expression or H. pylori infection alone. Whats more, they found that expansion of these Muc4-expressing pit cells requires H. pylori-driven gastric inflammation and that these cells also express amphiregulin, an epithelial cell protein involved in cell growth and wound healing. But is any of this relevant to gastric cancers in patients? Strikingly, it appears soOBrien and colleagues found MUC4-expressing pit cells in human gastric cancer tissue samples, where they appear to increase in number over the course of disease progression and co-express markers of high cell proliferation. Future work will test whether this cell type helps drive active disease.

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A new cell type with links to gastric cancer steps up for its mugshot - Fred Hutch News Service

Cell Biology

Programmed cell death may be 1.8 billion year – EurekAlert

Apoptosis, often referred to as programmed cell death, is a fundamental process crucial to the growth and development of multicellular organisms. This process, or a primordial form of it, is also observed in single-celled eukaryotes like yeast and other microeukaryotes (aka protists). The origin of eukaryotic apoptosis remains an open question in biology. However, studies have noted that many apoptosis-initiating factors have a bacterial or mitochondrial origin, providing a clue into the evolutionary history of this widespread phenomenon. In a new study published in Genome Biology and Evolution, scientists from the Institute of Biochemistry and Biophysics of the Polish Academy of Sciences reveal that many apoptotic factors may trace their origins to the time of mitochondrial domestication, suggesting remarkable conservation over the span of 1.8 billion years.

The processes triggering apoptosis exhibit striking similarities among various diverse eukaryotes: an increase in mitochondrial membrane permeability sets in motion a cascade of events involving proteins called apoptosis-inducing factors (AIFs), kickstarting the pathway that culminates in cell death. According to phylogenetic analyses, these AIFs usually have a bacterial/mitochondrial origin. To shed further light on the evolution of apoptosis across eukaryotes, a team led by Szymon Kaczanowski and Urszula Zielenkiewicz investigated the functional conservation of apoptotic factors through a yeast complementation test. The researchers replaced each of four apoptotic genes in yeast with related proteins from diverse eukaryotes and prokaryotes. They then treated the new yeast strains with apoptosis-inducing agents to evaluate whether the introduced genes maintained the ability to induce apoptosis in yeast.

Remarkably, the study found that distantly related proteins from plants, animals, slime molds, and bacteria were largely able to functionally substitute for the original yeast proteins. This surprising finding suggests that ancient mechanisms of cell death have been evolutionarily conserved since the domestication of mitochondria, says Kaczanowski and Zielenkiewicz, an event that occurred approximately 1.8 billion years ago.

The studys findings further support an endosymbiotic origin of apoptosis, a hypothesis that was first proposed by Guido Kroemer in 1997. Kroemer suggested that the bacterial precursors of mitochondria produced both toxins (apoptotic factors) and antitoxins (anti-apoptotic factors). In this scenario, the antitoxins acted as addiction molecules, ensuring the persistence of the symbiont. Driven by this evolutionary conflict between bacterial endosymbionts and hosts, the toxins eventually evolved into the apoptotic factors we recognize today.

Kaczanowski and Zielenkiewicz present an alternative scenario for the evolution of apoptosis. They propose that early protoeukaryotes were predators, relying on bacterial prey. These bacteria, in response to predation, produced toxins as a defense mechanism. Over time, these bacteria were domesticated to serve as mitochondria within eukaryotic cells, and their toxins evolved into apoptotic factors. The different families of AIFs present today and their sporadic distribution across distantly related eukaryotes suggest the existence of multiple redundant toxins in the protomitochondria and hint at a coevolutionary arms race between protomitochondria and their protoeukaryotic hosts.

Regardless of whether apoptosis originates from an endosymbiotic toxin/antitoxin system or from a predator/prey dynamic, the studys findings suggest that the intricate balance between life and death within eukaryotic cells is deeply rooted in the origin of mitochondria, opening up new avenues for research into the coevolution of mitochondria and eukaryotes, as well as the ancient origins of cell death mechanisms. Furthermore, a similar approach could be used to look at other ancient cellular mechanisms beyond programmed cell death and to ask to what extent conflicts among partners/participants have driven the evolution of genome features. Future studies may reveal the evolutionary history of other aging mechanisms and could make a significant contribution to aging studies, note Kaczanowski and Zielenkiewicz, emphasizing the broader implications of their research.

Genome Biology and Evolution

Observational study

Cells

Apoptotic Factors Are Evolutionarily Conserved Since Mitochondrial Domestication

11-Oct-2023

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Programmed cell death may be 1.8 billion year - EurekAlert

Cell Biology

New study confirms presence of flesh-eating and illness-causing … – Science Daily

When Hurricane Ian struck southwest Florida in September 2022, it unleashed a variety of Vibrio bacteria that can cause illness and death in humans, according to a new study published in the journal mBio.

Using a combination of genome sequencing and satellite and environmental data, a team of researchers from the University of Maryland, the University of Florida and microbiome company EzBiome detected several pathogenic Vibrio species in water and oyster samples from Florida's Lee County, a coastal region that was devastated by Hurricane Ian. The samples, which were collected in October 2022, revealed the presence of two particularly concerning species: Vibrio parahaemolyticus and Vibrio vulnificus.

"We were very surprised to be able to detect -- without any difficulty -- the presence of these pathogens," said the study's senior author Rita Colwell, a Distinguished University Professor in the University of Maryland Institute for Advanced Computer Studies (UMIACS) who has studied Vibrio for the last 50 years.

The study's findings correspond with a reported increase in V. vulnificus cases in the state of Florida in October 2022. According to the Florida Department of Health, Lee County, which had the highest caseload in the state, reported 38 infections and 11 deaths linked to vibriosis.

Vibrio bacteria naturally occur in the ocean, where they live symbiotically with crustaceans, zooplankton and bivalves. When the bacteria come in contact with humans, some species can cause an infection known as vibriosis, but the side effects depend on the type of Vibrio and severity of the infection. V. parahaemolyticus can cause gastroenteritis and wound infections, while the V. vulnificus species can cause necrotizing fasciitis -- a flesh-eating infection -- and kills 1 in 5 infected people.

People can contract vibriosis by eating raw or undercooked seafood or by getting seawater in an open wound. Because Vibrio thrive in warm saltwater, hurricanes and floods can increase the chances of a person becoming exposed.

Several conditions during and after Hurricane Ian favored the growth of Vibrio bacteria, including the amount of rainfall, changes in sea surface temperature and concentrations of chlorophyll in the ocean, which can indicate densities of phytoplankton -- and subsequently zooplankton -- in an area. In places with plankton blooms, the researchers found an abundance of Vibrio bacteria.

With warming oceans expected to fuel wetter and more powerful storms like Ian, coastal communities could see more Vibrioinfections in the future.

"These Vibrios generally grow well between 15 and 40 degrees Celsius [59-104 degrees Fahrenheit], so as the temperature warms, their generation time shortens and they divide faster and faster," Colwell said. "The warming of seawater -- which mixes with freshwater, creating optimal salinities -- really enhances the growth of Vibrios, so it's a very serious concern."

While the environmental conditions in Florida following Hurricane Ian were ripe for vibriosis, these cases are not limited to southern climes. In August 2023, three people in New York and Connecticut died from V. vulnificus infections.

Colwell and her co-authors -- which included Kyle Brumfield (Ph.D. '23, marine estuarine environmental sciences) and UMD Cell Biology and Molecular GeneticsResearch Professor Anwar Huq -- predicted this recent spike in vibriosis cases based on trending environmental conditions in the Northeast United States. As ocean temperatures continue to rise, Colwell said the rapidly warming Chesapeake Bay could also be affected.

"The waters are much warmer in Florida right now than they are in the Chesapeake Bay, but on a lot of the East Coast, the waters are warming," Colwell said. "This is a threatening indication that we may be seeing more Vibrio vulnificus infections.

Colwell and her co-authors noted that while they analyzed only a limited number of samples, their findings illustrate the potential of genetic analysis, environmental data and remote sensing to improve public health by proactively detecting and characterizing Vibrio pathogens.

They also called for further investigation to quantify the prevalence of Vibrio bacteria in different locations, seasons and environmental conditions. Colwell said this research is not only vital to public health but also an important step in understanding our changing climate.

"On the positive side, knowing that these infections are associated with the increased variability of a changing climate, perhaps now is the time to develop mechanisms to understand and mitigate it," Colwell said. "Climate change and flooding are clearly linked to infectious disease, and we need to take it seriously."

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New study confirms presence of flesh-eating and illness-causing ... - Science Daily

Cell Biology

New Institute for Immunologic Intervention (3i) at the Hackensack … – Hackensack Meridian Health

The new Institute aims to harness and boost immunity to tackle health puzzles - and is already supported by a generous gift from a donor

The Hackensack Meridian Center for Discovery and Innovation (CDI) has formed a new institute aiming to fight infections, cancer, and inflammatory diseases by finding a better way to restore and bolster the human immune system in its responses to disease.

The Institute for Immunologic Intervention (or 3i) is searching for ways to unleash new advances in immunology to beat disease and save lives. The expert scientists in this new institute include basic researchers, physician-scientists, and leading clinicians who are working seamlessly to tackle major health problems of our time.

The Institute is dedicated to advancing the understanding of fundamental mechanisms of infectious immunity, tumor immunity, alloimmunity, and autoimmunity within clinical contexts. By fostering collaborations with the CDI, the John Theurer Cancer Center at Hackensack University Medical Center and its consortium partner Georgetown Universitys Lombardi Comprehensive Cancer Center, and beyond, the 3i strives to apply this knowledge towards innovative strategies that enhance the effectiveness of cancer immunotherapy, interventions for autoimmune and alloimmune conditions, and the prevention of infections.

We have recruited world-class talent to give this Institute critical mass, said David Perlin, Ph.D., chief scientific officer and executive vice president of the CDI, and professor of medical sciences at the Hackensack Meridian School of Medicine. These scientists are tackling disease at the basic level of discovery - but with an eye toward finding real-world solutions in the near future. This is what the CDI is all about. Perlin is also a professor at Georgetown University.

We are excited about the possibilities - and also about the collaborations already happening among this group of scientists, said Binfeng Lu, Ph.D., the director of the 3i.

The scientists whose work is critical to the 3i, and their fields of expertise, include: Lu: cancer immunology and immunotherapy, and inflammatory biology; Yi Zhang, M.D., Ph.D.: (CAR) T cell biology, tumor immunity and alloimmunity; Hai-Hui Howard Xue, M.D., Ph.D.: T cell biology, tumor immunity; Johannes Zakrzewski, M.D.: cancer immunotherapy and immunosurveillance; Rachel Rosenstein, M.D., Ph.D.: inflammatory and fibrotic diseases; Sivia Lapidus, M.D., M.D.: pediatric rheumatic conditions and autoinflammatory disorders; Jigar V. Desai, Ph.D.: innate immunity, fungal infections; Benjamin Tycko, M.D., Ph.D.: genetics and epigenetics in human development and disease; Rena Feinman, Ph.D.: influence of the gut microbiome on antitumor immunosurveillance in patients with multiple myeloma (MM); Kevin Tong, Ph.D.: modeling the genetic progression of colorectal cancer for targeted therapies and personalized medicine; and Alvin Makohon-Moore, Ph.D.: evolutionary dynamics of cancer.

Virtually all of these 3i scientists also have faculty appointments at the Hackensack Meridian School of Medicine.

The research cores supporting the 3i include flow cytometry, microscopy, tissue biorepository bank, bioinformatics and statistical analysis, gene-editing, computational chemistry, and clinical immunology assays, among other expertise.

The expertise brought together in this one Institute at the CDI is a thrilling development, said Ihor Sawczuk, M.D., FACS, president of Academics, Research and Innovation for Hackensack MeridianHealth, the founding chair of the Hackensack MeridianHealthResearch Institute (HMHRI) of which CDI is part, and also associate dean of clinical integration and professor and chair emeritus of urology at the Hackensack Meridian School of Medicine. Working across an ecosystem like this is what will drive our science forward.

The 3i laboratories are all supported by federal grants. Most recently, in support of this mission, the 3i received a philanthropic grant in the amount of $500,000 to support the Institutes work in immunology and multiple myeloma research from the DAloia Family Foundation, led by G. Peter DAloia, an accomplished business executive who previously worked at several large national corporations, and his wife Marguerite. Mr. D'Aloia previously made a major gift to Hackensack Meridian Ocean University Medical Center.

I believe that the CDI has a great approach to finding cures for some of todays most difficult diseases, in particular its work on using the bodys immune system to fight cancer and its focus on treatment and cures for multiple myeloma, said Peter DAloia. It is my hope that this gift provides meaningful help in allowing the CDI to continue the good work being done within the organization.

To make a gift in support of the Institute for Immunologic Intervention (3i) at CDI, please visitGiveHMH.org/CDIor call William Evans, executive director at the CDI, atwilliam.evans@hmhn.orgor 201-880-3100.

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New Institute for Immunologic Intervention (3i) at the Hackensack ... - Hackensack Meridian Health

Cell Biology

Post-doctoral Fellow in Cancer Biology in the Department of … – Times Higher Education

Work type:Full-time Department:Department of Pathology, School of Clinical Medicine (21200) Categories:Senior Research Staff & Post-doctoral Fellow

Applications are invited for appointment asPost-doctoral Fellow in Cancer Biology in the Department of Pathology(Ref.: 523404), to commence as soon as possible for three years, with the possibility of renewal subject to satisfactory performance.

Applicants should have a Ph.D. degree, preferably in cancer biology, molecular biology, cellular biology, immunology, or chemistry-related fields. Research experience involving animal work, cell culture, mass spectrometry, and/or molecular biology would be an advantage. Applicants should be attentive to details, self-motivated, organized, able to multi-task, and able to work independently as well as in a team. The appointee will work with Dr. Carmen Wong on projects related to cancer immunology, cancer metabolism, tumor microenvironment, and/or hypoxia. Enquiries about the post should be sent to Dr. Carmen Wong atcarmencl@pathology.hku.hk.

A highly competitive salary commensurate with qualifications and experience will be offered, in addition to annual leave and medical benefits.

The University only accepts online application for the above post. Applicants should apply online and upload an up-to-date C.V. Review of applications will start on October 20, 2023 and continue untilDecember 31, 2023, or until the post is filled, whichever is earlier.

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Post-doctoral Fellow in Cancer Biology in the Department of ... - Times Higher Education

Cell Biology

Scientists uncover key enzymes involved in bacterial pathogenicity – News-Medical.Net

Gram-negative bacteria cause a variety of infectious diseases in plants and animals alike. Outbreaks of Salmonella and E. coli infections often make headlines due to their severity, and people have to resort to allopathic as well as natural remedies, increasing the burden on the healthcare system. While antibiotics offer an effective solution against bacterial infections, the increasing incidence of antibiotic-resistant bacteria have prompted researchers to identify other possible treatments against these infections. With technological advances and modern medicine, researchers are looking into the possibility of disrupting the pathogenicity of the bacteria at a molecular level by interfering with molecular processes at the gene as well as protein level.

Gram-negative bacteria, notorious for their infection capability, produce osmo-regulated periplasmic glucans (OPGs)-;long-chain carbohydrates made of multiple glucose units-;in the extracellular and/or periplasmic space. Initially, it was believed that OPGs were by-products produced under low solute concentrations, but recent reports confirm that they are crucial for pathogenicity, symbiosis, cell adhesion, and signaling.

However, the enzymes involved in the synthesis, regulation, and degradation of OPGs are not fully known. Genetic analysis revealed that the removal of opgH and/or opgG genes, partially responsible for OPG synthesis, causes bacteria to lose their infection capability, suggesting strong potential links of these genes with bacterial pathogenicity.

Although the structure of OpgG from E. coli (EcOpgG) has been elucidated, the mechanism of action of OpgG and OpgD from E. coli (EcOpgG and EcOpgD, respectively) remains unclear. Understanding the enzymes involved in OPG synthesis and the mechanisms underlying their function could provide us vital insights into the pathogenicity of Gram-negative bacteria, allowing us to develop more effective ways to deal with bacterial infections.

To bridge this gap in knowledge, Mr. Sei Motouchi from Tokyo University of Science, Dr. Kaito Kobayashi from the National Institute of Advanced Industrial Science and Technology (AIST), Associate, Associate Professor Hiroyuki Nakai from Niigata University and Professor Masahiro Nakajima from the Tokyo University of Science conducted structural and functional analyses of EcOpgD and EcOpgG. The study was published in Communications Biology on September 21, 2023.

Sharing the motivation behind this study, Professor Nakajima tells us, "Glycans are important biological macromolecules that play a variety of roles in living organisms, including pathogenicity and symbiosis. Their structure is very diverse and complex, and thus there are many types of enzymes that may synthesize and degrade them. However, we humans know only a small fraction of them".

The researchers investigated the functions of OPG-related genes in the model organism E. coli. Functional analyses revealed that E. coli OpgD (EcOpgD) was an endo--1,2-glucanase, which specifically broke down -1,2-glucans. It also had similar kinetic properties as those of general glycoside hydrolases (GH), further confirming its identity as a -1,2-glucanase.

Structural analysis using crystallography revealed a high degree of similarity between the structures of EcOpgG and EcOpgD. However, the two enzymes had remarkably different activity. Upon further investigation, the researchers found that a few amino acids forming the reaction pathway, termed 'Loop A', were critical for enzyme activity and regulated the rate of reaction. EcOpgG and EcOpgD differed in their catalytic functions, possibly due to the difference in the amino acids in the Loop A region. The LoopA region diversifies among this group of enzymes, which may lead to functional diversity. Nevertheless, the basis of the catalytic center is shared in this group of enzymes. This common point will help scientists develop therapies that could potentially disrupt OPG synthesis and hinder the infection capability of bacteria.

Further, while the two enzymes belonged to the same family of GHs, their structure did not match with any of the existing GH enzymes. Thus, the authors confirmed that they belonged to a novel GH family, namely GH186. This information opens avenues for research into therapies that can target GH186 proteins to stop the progression of bacterial infections.

Professor Masahiro concludes by explaining the long-term applications of the study, "Although it was known that some Gram-negative plant pathogens synthesize OPGs for pathogenicity, most of the key enzymes for their synthesis had not been identified, preventing the development of agrochemicals targeting OPGs. We have identified a family of enzymes (GH186) involved in the direct synthesis of OPGs and elucidated their detailed functions, which has presented us with new targets (GH186) to inhibit pathogens and provides a solid foundation for 'structure-based pesticide discovery'".

The findings of this study lay down a strong foundation for further investigation of OPGs and related genes and may usher in a new era of disease management.

Source:

Journal reference:

Motouchi, S., et al. (2023). Identification of enzymatic functions of osmo-regulated periplasmic glucan biosynthesis proteins from Escherichia coli reveals a novel glycoside hydrolase family. Communications Biology. doi.org/10.1038/s42003-023-05336-6.

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Scientists uncover key enzymes involved in bacterial pathogenicity - News-Medical.Net

Cell Biology

B cell response after influenza vaccine in young and older adults – EurekAlert

image:

Figure 1.Experimental workflow and subject demographics.

Credit: 2023 Wang et al.

[...] our findings suggest that the age-related decrease in response following influenza vaccination could reflect functional alterations in activated B cells [...]

BUFFALO, NY- October 10, 2023 A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 18, entitled, High-throughput single-cell profiling of B cell responses following inactivated influenza vaccination in young and older adults.

Seasonal influenza contributes to a substantial disease burden, resulting in approximately 10 million hospital visits and 50 thousand deaths in a typical year in the United States. 70 - 85% of the mortality occurs in people over the age of 65. Influenza vaccination is the best protection against the virus, but it is less effective for the elderly, which may be in part due to differences in the quantity or type of B cells induced by vaccination. In their new study, researchers Meng Wang, Ruoyi Jiang, Subhasis Mohanty, Hailong Meng, Albert C. Shaw, and Steven H. Kleinstein from Yale University / Yale School of Medicine investigated this possibility.

[...] we sorted pre- and post-vaccination peripheral blood B cells from three young and three older adults with strong antibody responses to the inactivated influenza vaccine and employed single-cell technology to simultaneously profile the gene expression and the B cell receptor (BCR) of the B cells.

Prior to vaccination, the researchers observed a higher somatic hypermutation frequency and a higher abundance of activated B cells in older adults than in young adults. Following vaccination, young adults mounted a more clonal response than older adults. The expanded clones included a mix of plasmablasts, activated B cells, and resting memory B cells in both age groups, with a decreased proportion of plasmablasts in older adults. Differential abundance analysis identified additional vaccine-responsive cells that were not part of expanded clones, especially in older adults.

To summarize, we showed a quantitative difference in B cell response following vaccination between age groups, with expansion dominated by plasmablasts in the young, and activated B cells in older adults. [...] Overall, this study provides insights into the B cell vaccine response differences between young and older adults and may be beneficial to design more effective vaccines in the older age groups.

Read the full paper: DOI: https://doi.org/10.18632/aging.204778

Corresponding Author: Albert C. Shaw, Steven H. Kleinstein

Corresponding Email: albert.shaw@yale.edu, steven.kleinstein@yale.edu

Keywords: B cell receptor, repertoire, clonal expansion, aging, single-cell RNA-seq

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About Aging:

Launched in 2009, Aging publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancerand now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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Observational study

People

High-throughput single-cell profiling of B cell responses following inactivated influenza vaccination in young and older adults

26-Jun-2023

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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B cell response after influenza vaccine in young and older adults - EurekAlert

Cell Biology

Post-doctoral researcher in yeast cell biology job with UNIVERSITY … – Times Higher Education

The De Wulf lab at the Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, Italy, is looking for an outstanding, highly motivated post-doctoral scientist to study the activity of a conserved oncogenic kinase in the budding yeast Saccharomyces cerevisiae. The research project wishes to understand how this kinase regulates (peri)centromeric chromatin and telomeres to ensure timely kinetochore assembly, chromosome transmission, and cellular aging.

For publications related to the topic, see: Bock LJ et al (2012) Nature Cell Biology, Iacovella MG et al (2015) Nature Communications, Iacovella MG et al (2018) Nucleic Acids Research, Berto G et al (2019) Current Genetics, Jurikov K et al. (2021) Trends in Genetics. More details of currently work (Nature Communications (2023), in press) and the proposed project itself will be gladly provided upon request.

Please visit our website for more information on the lab s research, and publications: http://www.cibio.unitn.it/510/chromosome-segregation-biology

The offer is a 1-year post-doctoral research contract, that can be further extended after the first 1-year evaluation.

Read more here:
Post-doctoral researcher in yeast cell biology job with UNIVERSITY ... - Times Higher Education