From probing the human brain to elucidating mechanisms behind cellular responses, Feinberg investigators have provided stunning new snapshots of biological processes invisible to the naked eye.
Here are some of the most striking images of the year.
Discovering a New Therapeutic Target for Pediatric Brain Cancers
Northwestern Medicine investigators have discovered that targeting a protein called TIM3 may increase survival compared to current immunotherapies in pediatric brain cancers.
The findings in mouse models of low-grade astrocytoma were published in the Journal of Clinical Investigation and highlight a new therapeutic target for treating children with these tumors who have exhausted all other treatment options.
“This study lays the translational groundwork for a clinical trial of anti-TIM3 therapy in pediatric patients with pilocytic astrocytoma who are in dire need of therapeutic strategies,” said Michael DeCuypere, MD, PhD, assistant professor of Neurological Surgery in the Division of Pediatric Neurological Surgery and co-senior author of the study.
Amy Heimberger, MD, PhD, the Jean Malnati Miller Professor of Brain Tumor Research and vice chair for Research in the Department of Neurological Surgery, was also a co-senior author of the study.
Caption: A high-magnitude image displaying TIM3 surrounding blood vessels in a murine model of pilocytic astrocytoma. Courtesy of Shashwat Tripathi.
Identifying Molecular Mechanisms of Rare Neurodevelopmental Disorder
Investigators from the laboratory of Alicia Guemez-Gamboa, PhD, assistant professor of Neuroscience, have discovered new molecular mechanisms of PACS1 syndrome, a rare neurodevelopmental disorder, according to findings published in Nature Communications.
PACS1 syndrome is characterized by intellectual disability and distinct craniofacial abnormalities. Patients may also experience epilepsy, autism, hypotonia (muscle weakness), feeding difficulties, and heart defects. The disorder, which was first identified in 2012, is caused by a single sporadic variant in the PACS1 (phosphofurin acidic cluster sorting 1) gene.
“Most neurodevelopmental disorders result from many different variants, but with PACS1 syndrome all patients have the same one, so it’s a pretty unique situation,” said Lauren Rylaarsdam, PhD, a former graduate student in the Guemez-Gamboa laboratory and lead author of the study.
Caption: A cortical organoid made from healthy cells spontaneously develops neural precursor cells in a rosette pattern (orange) surrounded by postmitotic neurons (blue). Courtesy of Lauren Rylaarsdam, PhD.
‘Dancing Molecules’ Heal Cartilage Damage
In November 2021, Northwestern University investigators introduced an injectable new therapy, which harnessed fast-moving “dancing molecules,” to repair tissues and reverse paralysis after severe spinal cord injuries.
Now, the same research group has applied the therapeutic strategy to damaged human cartilage cells. In the new study, the treatment activated the gene expression necessary to regenerate cartilage within just four hours. And, after only three days, the human cells produced protein components needed for cartilage regeneration.
The investigators also found that, as the molecular motion increased, the treatment’s effectiveness also increased. In other words, the molecules’ “dancing” motions were crucial for triggering the cartilage growth process.
The study was published in the Journal of the American Chemical Society.
Caption: In new experiments, human cartilage cells treated with fast-moving dancing molecules made more collagen II (shown in red), a crucial component for regeneration. Cell nuclei are shown in blue/purple. Courtesy of the Stupp Research Group/Northwestern.
Subset of Neurons Allow Eyes to Detect Motion
Northwestern Medicine scientists have identified how a subset of neurons enable the eyes to perceive motion, according to a study published in Nature Communications, a discovery that reveals previously hidden complexities of how vision functions in mammals.
The findings represent a significant leap forward in understanding the mysteries of the visual system in mammals, said Yongling Zhu, PhD, assistant professor of Ophthalmology, of Neuroscience and senior author of the study.
We have uncovered that modular interneuron circuits play a pivotal role in fine-tuning the way mice perceive and react to moving objects, offering new insights into the field of visual neuroscience. Our approach is innovative in that it not only can be used to study motion perception, but it also sets the stage for future investigation into the other aspects of visual perception.” –Yongling Zhu
Caption: A new subtype of interneuron found in the retina plays a pivotal role within modular interneuron circuits, controlling whether to activate or suppress the object motion signal for downstream neurons in both the retina and the brain. Courtesy of Yongling Zhu, PhD.
Decorated Nanoparticles Prevent Allergic Reactions
Northwestern University scientists developed the first selective therapy to prevent allergic reactions, which can range in severity from itchy hives and watery eyes to trouble breathing and even death.
To develop the new therapy, published in Nature Nanotechnology, investigators decorated nanoparticles with antibodies capable of shutting down specific immune cells (called mast cells) responsible for allergic responses. The nanoparticle also carries an allergen that corresponds to the patient’s specific allergy. If a person is allergic to peanuts, for example, then the nanoparticle carries a peanut protein.
In this two-step approach, the allergen engages the precise mast cells responsible for the specific allergy, and then the antibodies shut down only those cells. This highly targeted approach enables the therapy to selectively prevent specific allergies without suppressing the entire immune system.
“The biggest unmet need is in anaphylaxis, which can be life-threatening,” said Bruce Bochner, MD, professor emeritus of Medicine in the Division of Allergy and Immunology and a co-author of the study. “Certain forms of oral immunotherapy might be helpful in some cases, but we currently don’t have any FDA-approved treatment options that consistently prevent such reactions other than avoiding the offending food or agent. Otherwise, treatments like epinephrine are given to treat severe reactions — not prevent them. Wouldn’t it be great if there was a safe and effective treatment for food allergy that consistently made it possible to reintroduce a food into the diet that you used to have to strictly avoid?”
Caption: A scanning electron microscope image of the nanoparticle (small sphere in center) inside a mast cell.
Antioxidant Gel Preserves Islet Function After Pancreas Removal
Northwestern University scientists have developed a novel antioxidant biomaterial that someday could provide much-needed relief to people living with chronic pancreatitis, according to a new study published in Science Advances.
Before surgeons remove the pancreas from patients with severe, painful chronic pancreatitis, they first harvest insulin-producing tissue clusters, called islets, and transplant them into the vasculature of the liver. The goal of the transplant is to preserve a patient’s ability to control their own blood-glucose levels without insulin injections.
Unfortunately, the process inadvertently destroys 50-80 percent of islets, and one-third of patients become diabetic after surgery. Three years post-surgery, 70 percent of patients require insulin injections, which are accompanied by a list of side effects, including weight gain, hypoglycemia and fatigue.
In the new study, scientists transplanted islets from the pancreas to the omentum — the large, flat, fatty tissue that covers the intestines — instead of the liver. To create a healthier microenvironment for the islets, the investigators adhered the islets to the omentum with an inherently antioxidant and anti-inflammatory biomaterial, which rapidly transforms from a liquid to a gel when exposed to body temperature.
Guillermo A. Ameer, ScD, professor of Surgery in the Division of Vascular Surgery and the Daniel Hale Williams Professor of Biomedical Engineering in the McCormick School of Engineering, was senior author of the study.
Caption: This image shows transplanted islets (darker purple) and the blood vessels (the red/dark pink areas are blood cells inside the blood vessels). Courtesy of Guillermo Ameer, ScD/Northwestern University.
Long-Lived Proteins Impact Aging of Female Reproductive System
For the first time, Northwestern Medicine scientists have identified a population of long-lived proteins in the ovaries which likely support the stability and longevity of the female reproductive system and may contribute to reproductive aging, according to a recent study published in the journal eLife.
To better understand the mechanisms that contribute to reproductive aging, Francesca Duncan, PhD, the Thomas J. Watkins Memorial Professor of Reproductive Science, and co-senior author of the study, teamed up with Jeffrey Savas, PhD, associate professor in the Ken and Ruth Davee Department Neurology in the Division of Behavioral Neurology, to study the impact of the loss of protein function and quality in the ovaries and in oocytes, or egg cells that have not yet matured.
We’ve generated a resource for the field because now we have a catalog of long-lived proteins that we and others can now go after to understand mechanistically how they are contributing to reproductive aging."–Francesca Duncan
Caption: Representative hue saturation intensity (HSI) mosaic from an ovary of a 15N-labeled mouse (six months of age). Localization and abundance of 15N varied depending on cell type. Courtesy of Francesca Duncan, PhD, and Jeffrey Savas, PhD.
New Huntington’s Treatment Prevents Protein Aggregation in Mice
In research published in Science Advances, scientists at Northwestern and Case Western Reserve universities have developed the first polymer-based therapeutic for Huntington’s disease, an incurable, debilitating illness that causes nerve cells to break down in the brain.
Nathan Gianneschi, PhD, professor of Pharmacology, was senior author of the study.
“Huntington’s is a horrific, insidious disease,” said Gianneschi, who led the polymer therapeutic development. “If you have this genetic mutation, you will get Huntington’s disease. It’s unavoidable; there’s no way out. There is no real treatment for stopping or reversing the disease, and there is no cure. These patients really need help. So, we started thinking about a new way to address this disease. The misfolded proteins interact and aggregate. We’ve developed a polymer that can fight those interactions.”
Caption: Patients with Huntington’s disease have a genetic mutation that triggers proteins to misfold and clump together in the brain. These clumps interfere with cell function and eventually lead to cell death. The new treatment leverages peptide-brush polymers, which act as a shield to prevent proteins from binding to one another. The polymer backbone is shown in yellow. Active peptides are blue and green. Courtesy of Nathan Gianneschi, PhD/Northwestern University.
Engineering Human Heart Tissue for Scientific Study
Northwestern Medicine scientists have developed a new way to measure heart contraction and electrical activity in engineered human heart tissues, according to findings published in Science Advances.
For years, heart research has been limited by a lack of cell models and has relied on animal models to substitute for human hearts, said Elizabeth McNally, MD, PhD, the Elizabeth J. Ward Professor of Genetic Medicine, who was co-senior author of the study.
“We need cells that actually beat and have electrical properties,” said McNally, who also leads the Center for Genetic Medicine. “We can collect blood cells from patients with genetic disease and turn them into stem cells in the dish. From these stem cells, we build three-dimensional engineered heart tissues that we can now carefully monitor. These models have many of the properties of human hearts.”
Caption: The engineered heart tissues were grown in a ring to better mimic live human hearts. Courtesy of Dominic Fullenkamp, MD, PhD.
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Credits:
Olivia Dimmer and Melissa Rohman