Latest news with #TheHormelInstitute
Yahoo
17-05-2025
- Health
- Yahoo
Mixed cellular signals? Cellular antennae could be cancer treatment fix
May 16—A cell's primary cilia function like antennae. Operating like a 24/7 news outlet, these hairlike structures are present on the surface of all animal cells, where they receive signals or information from the outside environment and deliver them inside the cell. Researchers in the lab of Sergio Gradilone, PhD, professor at The Hormel Institute, University of Minnesota, have discovered that these primary cilia have a connection to an important information delivery system known as the epidermal growth factor receptor (EGFR) signaling pathway. This EGFR pathway sends a signal to the cell and triggers it to grow and divide. Then, the cell's receptor is destroyed or degraded, which removes the signal and prevents the cell from further growth and division. Capitalizing on this connection could lead to more effectively treating diseases such as polycystic liver disease or cholangiocarcinoma, as well as broader applications for other cancer types. "What we discovered is that in normal cells, the receptors need to first move, or translocate, to the primary cilia, and from there, it's degraded. When you have tumor cells or different cells that have defects in primary cilia, that translocation is not happening. So, the receptor remains active for a longer time, and is telling the cell to keep growing," Gradilone said. This continued cell growth can result in cancerous and polycystic cells multiplying at uncontrolled, uninterrupted rates. This work by the Gradilone research group has been published in a paper appearing in the scientific journal Hepatology, which explores the relationship between a cell's primary cilia and this EGFR process that stimulates cells to grow and divide. While this study focuses primarily on bile duct cells and has possible treatment applications for diseases such as cholangiocarcinoma and polycystic liver disease, there are broader possible applications for other cancer types as well, such as breast, prostate, and colon cancers, which also experience primary cilia loss. When a normal cell transforms into a tumor cell, it loses primary cilia. EGFR overexpression and active mutations are commonly found in different tumors—but if there were an alternative approach to cause the destruction of the EGFR receptor, that could lead to significant developments in designing more effective treatments for cancer and polycystic diseases. A therapeutic approach known as "ciliotherapy" would involve inhibiting the activity of EGFR by putting cilia back in tumor cells where they belong. The Gradilone researcher group's discoveries tied to the EGFR signaling pathway offers exciting new insights that further describe this important role that cilia play in stopping the EGFR signal. "We now have more knowledge about how tumor cells remove the cilia. So we can stop that process, put the cilia back, and now, the cell's primary cilia is acting in a normal way. So we terminate the uncontrolled growth signal that is coming from the receptor," Gradilone said. The study publication, titled "Cholangiocyte ciliary defects induce sustained epidermal growth factor receptor signaling," was authored by Gradilone research group members Kishor Pant PhD, Seth Richard, Estanislao Peixoto, PhD, and Subheksha Baral, in collaboration with researchers at Mayo Clinic and Northwestern University Feinberg School of Medicine.
Yahoo
03-05-2025
- Health
- Yahoo
Scientists identify strategy to boost mitochondrial function, improve immunotherapy treatment
May 2—Despite the massive successes of immunotherapy, which utilizes the body's immune system as a tool to fight cancer, therapy resistance is still a common treatment obstacle for many patients with solid tumors. With a new paper in the leading scientific journal Cell Metabolism, the lab of Vivek Verma, PhD, assistant professor at The Hormel Institute, University of Minnesota, outlines a pharmacological method to boost mitochondrial function in cells that could be easily translated to clinics, enhancing immunotherapy treatments for better outcomes in patients. "This study has huge implications in reversing the resistance of cancer patients to various immunotherapies," Verma said. "Our study provides a direct link between cell metabolism and gene expression, especially in mitochondria." The cancerous tumor microenvironment is a hostile one, especially to an immune cell's powerhouse: the mitochondria. Signals given off in this microenvironment can interfere with nutrition, inhibit mitochondrial function, and lead to immune cell exhaustion. With little to no energy, immune cells are unable to actively fight off pathogens, infections, and cancerous cells. Mitochondrial function is also essential for the process of T cells transitioning from their naive phase to the effector phase—when these immune cells begin actively fighting off pathogens or cancerous cells. Currently, there are not yet any clinically viable strategies that can be used to target mitochondria to ensure it retains the power necessary to fight off disease, including cancer. In the Cell Metabolism paper, Verma and the team found that activating the enzyme PKM2 helped boost mitochondrial metabolism in anti-tumor CD8 T cells. Additionally, the team learned that CD8 T cells with activated PKM2 also displayed better efficacy in adoptive cell models and in combination with immune checkpoint-based immunotherapy. "Surprisingly, the roles of PKM2 in CD8 T cells had not yet been established. In this study, we show for the first time that pharmacological activation of PKM2 leads to mitochondria-mediated enhancement of effector functions in CD8 T cells," Verma said. "Also surprisingly, we found that PKM2 modifies cell metabolism that regulates the expression of genes located on mitochondrial DNA. Our study provides a direct link between cell metabolism and gene expression, especially in mitochondria."
Yahoo
30-04-2025
- Health
- Yahoo
Breakthrough EMBO Journal study generates never-before-seen insights on a protein critical for chemotherapy
Apr. 29—AI can be a powerful tool in research, but it's not the be-all, end-all—and a new study led by Amer Alam, PhD, associate professor at The Hormel Institute, University of Minnesota, is a prime example of the power of people and direct experimentation in scientific research. Appearing in The EMBO Journal, the breakthrough study reveals new information about a protein called ABCB1—including a never-before-seen structure in significant contrast to AI modeling predictions. The protein plays a key role in drug resistance, a major challenge in oncology, and the new insights from this study may hold the key for developing more effective pharmacological treatments for cancer, Alzheimer's disease, and more. "Given its critical role in medicine and drug development, ABCB1 has been extensively studied, yet key details about its function have remained elusive. Our findings bridge longstanding gaps in understanding how this protein interacts with lipids and drugs, helping to reconcile decades of genetic and cellular studies," Alam said. "The structural data we present sets a new benchmark for ABCB1 research and will have widespread implications for the fields of pharmacology, structural biology, and drug discovery." Using The Hormel Institute's cryogenic-sample electron microscopy (cryoEM) technology, the research team generated high-resolution, 3D snapshots of ABCB1 in four different states—including in its never-before-seen resting state, which, despite decades of research, has been unknown until now. The ability to take an even closer look at ABCB1 revealed a completely new shape with previously unrecognized features that challenge prior assumptions based on similar proteins. "Surprisingly, our experimentally determined structure [of ABCB1 in its "apo" state] differs significantly from predictions made by AlphaFold, a leading AI-based protein modeling tool. This discovery highlights the current limitations of computational models and underscores the importance of direct experimental validation," Alam said. "Our findings also distinguish how certain drugs interact with ABCB1, either as transportable compounds or as inhibitors that lock the protein in specific states." A family of proteins known as ATP-binding cassette (ABC) transporters move substances like sugars, lipids, amino acids, and pharmaceutical drugs across cell membranes and into or out of cells or cellular organelles. ABCB1—also known as Multidrug Resistance Protein 1 (MDR1) or P-glycoprotein—is an ABC transporter that operates like a pump, ejecting foreign substances from cells to detoxify them. Its action can determine the fate of drug therapy by affecting drug uptake and clearance from cells, which has led to the Food and Drug Administration (FDA) requiring all new drug candidates to be screened for ABCB1 interactions. ABCB1 is most well-known for multidrug resistance (MDR). This is when cancer cells, in response to chemotherapy, can overproduce ABCB1, which actively pumps out the chemotherapeutic drugs and leads to therapy failure. MDR is considered a major hurdle when administering chemotherapy and can often become a contributing factor toward cancer deaths. Post-Doctoral Associate Devanshu Kurre, PhD, Research Associate Phuoc X Dang, Post-Doctoral Associate Le Thi My Le, PhD, are also listed as authors of the paper. This research was supported in part by Eagles Cancer Postdoctoral Fellowships awarded to Dr. Kurre and Dr. Le.
Yahoo
02-04-2025
- Health
- Yahoo
Institute researchers find links between exposure to Carcinogens and aromatics released from gasoline
Apr. 1—Leena Hilakivi-Clarke, PhD, professor at The Hormel Institute, University of Minnesota, is the author of a paper appearing in the scientific journal iScience titled "Aromatics from fossil fuels and breast cancer." In a review of existing scientific literature, researchers identified links between exposure to benzene, toluene, ethylbenzene and xylene (BTEX) aromatics and polycyclic aromatic hydrocarbons (PAHs) from fossil fuels and breast cancer risk in humans. Breast cancer rates continue to rise, especially in young women. Years of scientific research has shown breast cancer risk which runs in families is often caused by germline mutations — mutations in parental cells that are passed down to offspring. BRCA1 and BRCA2 are two of the most commonly known genetic mutations linked to inherited breast cancer risk. At the same time, more than 80% of breast cancers develop sporadically without any inherited mutations — and causes for these breast cancers have remained unknown. Several risk factors have been identified, such as timing of puberty onset and menopause, age at first pregnancy, diet and lifetime exposure to estrogens. However, these factors do not cause breast cancer, but alter vulnerability to environmental carcinogens that then can cause breast cancer. The Biofuels Research Project researchers have studied the carcinogenic (cancer-causing) effects of compounds originating from burning fossil fuels. In their newly published review of existing scientific literature, researchers identify exposure to PAHs from fossil fuels as key mutagens (compounds that can lead to DNA mutations) causing breast cancer in humans. Among their key findings: —Exposure to BTEX aromatics in fossil fuels may add to the adverse effects of PAH exposure. —Exposure to BTEX compounds early in life, including in utero, may increase susceptibility to PAH-initiated breast cancer. —Early life exposure to BTEX compounds may increase later breast cancer risk by silencing DNA repair mechanisms, increasing the number of targets in the breast that are known to be the sites where breast cancers are initiated (terminal lobular ductal units or TLDUs), and causing persistent gut dysbiosis (imbalance of healthy and harmful gut bacteria) which in turn impairs immune responses in the tumor microenvironment, preventing effector CD8+ T cells from killing cancer cells. "It is essential to reduce exposure to the products from burning fossil fuels to prevent breast cancer. We are studying if reducing BTEX exposure will reduce susceptibility to PAH induced breast cancer. One way to reduce BTEX compounds is to reduce exposure by adding ethanol to gasoline," Hilakivi-Clarke said. The Hormel Institute researchers Theresa Jolejole, PhD candidate; Joas Lucas da Silva, PhD, post-doctoral associate; and Fabia de Oliveira Andrade, PhD, senior scientist, are among the authors of the paper. The research project is supported by 15 different ethanol and biofuels funding agencies.
Yahoo
28-03-2025
- Health
- Yahoo
Institute scientists are optimizing data for more precise cancer diagnosis, treatment
Mar. 27—David Guinovart, PhD, and Eric Rahrmann, PhD, assistant professors at The Hormel Institute, University of Minnesota, are the recipients of a two-year, $100,000 Data Science Initiative (DSI) Seed Grant from the University of Minnesota. Their funded project, MOOBI: Multi-Omics Optimization-Based Integration for Enhanced Cancer Research Datasets, aims to tackle key challenges in integrating multi-omics data for more precise breast cancer diagnosis and therapeutic targets. Multi-omics is a biological analysis approach that makes use of multiple types of datasets. In this project, Guinovart and team are leveraging data made publicly available from The Cancer Genome Atlas (TCGA). They aim to develop a new, integrated dataset with the ultimate goal of enhancing breast cancer subtype classifications and identifying biomarkers for diagnosis and therapeutic targets. This means patients could have a higher likelihood of being matched with the right treatment options for the right cancer as early as possible. With his background in applied mathematics, Guinovart sought Rahrmann's expertise in cancer biology and metastasis for this interdisciplinary collaboration. "The way we see this collaboration is an integrative process: we develop an idea, Eric will offer his ideas, and we will adjust as needed. It keeps the model not only accurate, but also fresh," Guinovart said. "In this particular case, we are trying to add more information to this already available data, developing a model that can respond to real-life problems more effectively. I think this could be used for other opportunities, but we will also have a clean dataset that has been validated at another level. We will also be able to share this ready-to-use data to fit other models, ideas, or research." With Guinovart an applied mathematician and Rahrmann an expert in developmental biology, cancer biology and metastasis, this endeavor is a collaboration that helps keep the ideas considered and models developed accurate and fresh. "Too often, we only look at the tip of the iceberg and ignore the rest of the data. Essentially, we're going back with these new, innovative approaches to revisit old questions and ultimately identify new biomarkers and therapeutic targets," Rahrmann said. The project also holds potential for broader applications in the future. Rahrmann said that the data may be helpful in identifying transition phases of cancer toward hybrid cancer types at critical times of disease progression. The TCGA has a treasure trove of data — 2.5 petabytes, in fact, or 2.5 million gigabytes — that has been gathered over decades of research. With so much information at hand, projects like this can find new connections and applications that have yet to be discovered. Once the research team has its refined, well-structured data, they will feed that data to machine learning models that use multiple parameters for optimized classification to minimize false positives in cancer diagnosis as much as possible. Post-Doctoral Associate Mohammed Qaraad, PhD, and Senior Scientist Kayum Alam, PhD, are also contributing to the project.
