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Medscape
5 days ago
- Health
- Medscape
From Lab to Landmark Therapy: Meet the Woman Behind GLP-1
Svetlana Mojsov, PhD Biochemist Svetlana Mojsov, PhD, has been awarded the Frontiers of Knowledge Award in Biology and Biomedicine, presented by Spain's BBVA Foundation, for her collaborative research with Daniel Drucker, Joel Habener, and Jens Holst. Their work revealed the biological function of the hormone GLP-1, a key regulator of glucose metabolism and appetite. These discoveries paved the way for a new generation of therapies that have transformed the management of type 2 diabetes (T2D) and obesity, offering not only improved glycemic control and weight loss but also reduced cardiovascular risk. The findings have also sparked new lines of basic and translational research in multiple disease areas. Speaking to El Médico Interactivo , a Medscape Network platform, during the recent awards ceremony in Bilbao, Spain, Mojsov shared her perspective on the future of research. 'We are witnessing a new paradigm in which clinical experience is guiding future research to help us understand very fundamental concepts,' said Mojsov, currently a research associate professor at Rockefeller University in New York. How does it feel to see that drugs derived from your GLP-1 research are helping millions of people manage diabetes and obesity? I'm very happy to have contributed to something that has helped so many people. These drugs improve not only health outcomes but also overall quality of life. Being a scientist is a profession with many rewards — and certainly more benefits than setbacks — when your work can make a real difference. All scientists are driven by the goal of advancing knowledge and human health. I feel privileged to have been part of the early stages of this long scientific journey. Over the past two decades, GLP-1-based therapies have represented a major breakthrough in the treatment of T2D and obesity, improving both quality of life and clinical outcomes for millions of patients. For the first time, we've seen body weight reductions of up to 20% — which is particularly important because excess weight worsens the prognosis of T2D. Most earlier treatments actually caused weight gain, which limited their effectiveness. GLP-1 therapies, in contrast, help patients lose weight and improve disease outlook at the same time. What led you to investigate gut hormones, particularly GLP-1 and glucose-dependent insulinotropic polypeptide (GIP)? My interest in peptide-based therapies for glucose metabolism goes back to the mid-1970s, when I was a graduate student working with Dr Bruce Merrifield at Rockefeller University. We were studying the biology of glucagon — a hormone that raises blood glucose — and exploring how to synthesize glucagon analogs and inhibitors using solid-phase peptide synthesis. At that time, however, the available synthesis techniques often produced biologically inactive glucagon due to chemical modifications in the amino acid sequence. Merrifield encouraged me to develop new strategies to overcome this limitation, which laid the foundation for my later work on GLP-1. Were these the strategies you went on to explore in your research? Yes. For my doctoral thesis and later during my postdoctoral work, I focused on the amino acid sequence and biology of glucagon. That experience was instrumental in my discovery of GLP-1 in the early 1980s at Massachusetts General Hospital in Boston. In 1983, I identified the biologically active form of GLP-1 as a 31-amino acid peptide, which I named GLP-1 (7-37). I also hypothesized that it functioned as an incretin, a gut-derived peptide that stimulates insulin secretion in response to food intake. You and the other three awardees worked on the same hormone. Did you collaborate directly, or was the work conducted independently? How important is collaboration in this field? To detect GLP-1 (7-37) in the gut, I synthesized it myself in the endocrinology unit of my lab using solid-phase peptide synthesis. I also developed highly specific antibodies, radioimmunoassays, and chromatographic techniques that allowed me to confirm the presence of GLP-1 (7-37) at the site of incretin secretion. Although I conducted this initial work independently as a chemist, that kind of foundational research still requires close collaboration across disciplines. After identifying GLP-1 (7-37), I began working closely with Drs Joel Habener and David Nathan at Massachusetts General Hospital, and with Dr Gordon Weir at the Joslin Diabetes Center. So yes, throughout my work, I collaborated extensively with both biologists and clinical researchers. Your first GLP-1 findings date back to 1986. The first drugs came in 2005, and those widely used today appeared in 2017. Has the translation from discovery to clinic taken too long? What could be done to accelerate this process? You're right. Our early clinical studies with Nathan were the first to demonstrate that GLP-1 (7-37) stimulates insulin secretion and lowers blood glucose in people with T2D, establishing its therapeutic potential. Back at Rockefeller, my colleague Yang Wei and I showed that GLP-1 receptors are expressed not only in the pancreas but also in the brain, heart, and kidneys. This indicated that GLP-1's effects across these organs are mediated by a common receptor. In the 1980s and 1990s, the pharmaceutical industry was skeptical that peptides could become viable drugs because they required injection, and oral medications were strongly preferred by patients. Still, GLP-1 (7-37) held promise. In 2005, researchers discovered a longer-acting GLP-1-like peptide in lizard venom, which allowed Amylin Pharmaceuticals to act quickly since they didn't have to develop a new compound from scratch. That said, many companies were hesitant to invest in a peptide derived from a lizard. Twenty-five years after my original publications, Novo Nordisk and Lilly launched long-acting GLP-1 analogs. These drugs are now used to treat a wide range of conditions beyond T2D and obesity, including cardiovascular and renal disease and potentially even neurodegenerative disorders. It's the first time a single drug class has shown such broad therapeutic utility. Your discoveries are already benefiting millions of patients with obesity and diabetes, but cost remains a significant barrier. Do you think these drugs will become more accessible in low- and middle-income countries? They must become more affordable — otherwise, their usefulness is fundamentally limited. The broader the access, the greater the public health impact. I'm optimistic that continued innovation will help lower costs and improve global accessibility. These therapies shouldn't be reserved only for patients in wealthy nations. The health benefits must be shared more equitably. We also need to prioritize and protect scientific research. Especially given the current climate in the US, it's worth remembering that our longer, healthier lives are built on scientific progress. While the pharmaceutical industry plays a vital role, it all starts with discovery — and discovery starts in academic and research institutions. That's where we need to focus our support. Novo Nordisk did outstanding work, but they built on foundational research that came from the lab. Ultimately, we all have to work together. Every breakthrough starts with knowledge— knowledge, knowledge, and more knowledge. With T2D and obesity rising globally, and GLP-1 therapies now widely available, do you worry that they might shift attention away from prevention? No, quite the opposite. These therapies are most effective when combined with a commitment to overall health. Although some health conditions are unavoidable, I believe these drugs serve as a reminder of the importance of personal well-being. They help people take concrete steps toward better health. GLP-1 receptor agonists are now a key part of the pharmacologic toolkit for managing obesity and diabetes. Do you think they'll prove effective in other conditions, such as cardiovascular disease, neurodegeneration, or addiction? We already know they offer cardiovascular benefits, and physicians are prescribing them for people with diabetes — including those on insulin — because they also support kidney function. So these therapies are already broadly accepted and widely used. When it comes to neurodegenerative diseases, however, it's still too early to draw conclusions. Current findings are anecdotal and based on small patient cohorts. We need a much better understanding of the mechanisms involved. The same applies to addiction. There's speculation that GLP-1 analogs might help prevent addictive behaviors, but we need robust evidence before reaching that conclusion. This is the exciting part of science: knowledge opens the door to new discoveries. We need to return to the lab, use animal models, and uncover the mechanisms at work. Once we do, we'll be in a better position to confirm the full range of effects and explore new indications. You've had to fight for recognition on five patents. Do you believe being a woman made that more difficult? And do young women entering science today have equal opportunities? I grew up in Yugoslavia, where we weren't really taught to think in terms of gender differences. I never believed someone would take advantage of me for being a woman. Whether it happened or not, I can't say, but I never attributed any setbacks to my gender. I knew what I wanted and I fought for it. I pursued the patent issue because the original filing didn't properly reflect my contribution. My work resulted in five patents—four of which I secured after correcting Massachusetts General Hospital's initial application. Today, women are firmly part of the scientific community. Half of all researchers are women, so there should be no room for discrimination. That said, when something isn't right, we must speak up—clearly and confidently—and have the courage to stand our ground. Your perseverance and discipline are admirable. How important are those traits for aspiring researchers? They're both essential. This path is never easy.
Sustainability Times
02-07-2025
- Science
- Sustainability Times
'Human Gene Makes Mice Speak': Scientists Alter Rodents With Language DNA and Trigger Startling Changes in Vocal Behavior
IN A NUTSHELL 🧬 Scientists inserted the human-specific NOVA1 gene into mice, revealing significant changes in their vocalizations . gene into mice, revealing significant changes in their . 🔊 Modified mice produced higher-pitched squeaks and different sound mixes, providing insight into communication evolution. evolution. 🧠 The NOVA1 gene plays a crucial role in brain development and influences genes associated with vocalization . gene plays a crucial role in brain development and influences genes associated with . 🌍 This research enhances our understanding of human evolution and the genetic basis of advanced language skills. In a stunning leap for genetic research, scientists have managed to insert a human gene into mice, resulting in unexpectedly altered vocalizations. This groundbreaking experiment, conducted at Rockefeller University, has revealed that a small genetic change can have significant effects on communication. By introducing the human-specific NOVA1 gene into mice, researchers have opened new avenues for understanding the evolution of vocal communication, shedding light on how humans may have developed their advanced language skills. A Genetic Change That Alters Communication The NOVA1 gene is crucial for brain development and is present across many species, including mammals and birds. A unique variation of this gene is found only in humans, producing a protein vital for vocalization. At Rockefeller University, scientists introduced this human version of NOVA1 into mice to explore its role in communication. The findings were remarkable. Baby mice with the humanized NOVA1 gene exhibited different vocalizations compared to those with the typical mouse version. When calling to their mothers, these modified mice produced higher-pitched squeaks and a different mix of sounds. These changes are not just minor; they provide critical insights into how complex vocal communication might have evolved over time. This experiment underscores the potential for genetic modifications to influence communication patterns, offering a glimpse into the genetic basis of language evolution. 'Time Was Here First': Mind-Blowing Discovery Reveals the Universe Was Born from Time Itself, Not from Space at All The Role of NOVA1 in Mice Vocalization In their natural state, baby mice use ultrasonic squeaks to communicate with their mothers. Scientists categorize these sounds into four basic 'letters': S, D, U, and M. When the human version of NOVA1 was inserted, the modified mice's sounds differed significantly from wild-type mice. Some 'letters' in their squeaks changed entirely, indicating that the genetic modification influenced their ability to produce and potentially understand vocalizations. As these mice matured, the changes became more pronounced. Male mice, in particular, produced a wider variety of high-frequency calls during courtship. These alterations in vocal patterns suggest that genetic expression changes could impact the evolution of communication and behavior, providing a window into how complex communication systems might arise within a species. 'Google Just Changed Everything': This Ruthless New AI Reads 1 Million Human DNA Letters Instantly and Scientists Are Stunned NOVA1: A Key Player in Evolutionary Communication The NOVA1 gene encodes a protein involved in RNA binding, essential for brain development and movement control. While the human and mouse versions of NOVA1 function similarly, the human version uniquely affects genes related to vocalization. The study revealed that many genes associated with vocalization are binding targets of NOVA1, indicating the gene's direct role in regulating vocal communication. This ability to influence specific genes might explain why humans developed advanced language skills compared to other species. Human-Specific Genetic Variants and Evolution Interestingly, the human version of NOVA1 is absent in other hominin species like Neanderthals and Denisovans. These extinct relatives shared a similar NOVA1 version but lacked the human-specific variant causing the I197V amino acid change. This discovery enriches our understanding of human evolution and the origins of speech. 'Like a Floating Magic Carpet': Newly Discovered Deep-Sea Creature Stuns Scientists With Its Surreal, Otherworldly Movements Professor Robert Darnell, who led the study, speculated that this genetic shift may have given early humans an evolutionary advantage. Darnell noted, 'We thought, wow. We did not expect that. It was one of those really surprising moments in science.' This genetic change might have been crucial in allowing Homo sapiens to develop sophisticated communication skills, distinguishing them from other species. This insight prompts intriguing questions: Could enhanced communication abilities have been decisive for the survival and success of Homo sapiens? The researchers suggest that this NOVA1 shift could have been pivotal in our species' ability to thrive, while other hominins, lacking this trait, eventually declined. This groundbreaking research on the NOVA1 gene not only opens new paths for scientific inquiry but also raises critical questions about our own evolution. How might further understanding of such genetic shifts illuminate the path of human development, and could these insights lead to revolutionary advances in genetic medicine and therapy? Our author used artificial intelligence to enhance this article. Did you like it? 4.7/5 (26)
Time of India
23-06-2025
- Health
- Time of India
How dengue mosquitoes outsmart even scientists
How dengue mosquitoes outsmart even scientists - their secret hunting techniques revealed Chethan Kumar TNN Updated: Jun 23, 2025, 18:12 IST IST While the dengue mosquito is a smarter predator than previously thought — it can detect you with its legs, too — Indian scientists have detected that a stealthy group of immune cells could be the unsung heroes in fighting the infection It's tough to outsmart a mosquito out for your blood. Here's some consolation. The buzzing insect outsmarts even supersmart scientists. 'Aedes aegypti', the mosquito behind dengue , Zika, and yellow fever , hunts down its prey — humans — primarily by its sense of smell. So, when researchers from the Rockefeller University stripped Aedes aegypti of its primary olfactory gene, Orco — knocking out their sense of smell — they reckoned the female mosquito will lose her hunting instinct. But she was smarter than they were. As a new study published in Science Advances details, when deprived of their olfactory power, Aedes use their ability to sense body heat. Typically, it's the mosquito's antennae that detects odours and heat. But Orco mutants deploy their forelegs to detect human skin temperature.
Economic Times
23-06-2025
- Health
- Economic Times
Dengue mosquito is a much smarter predator than thought, it uses a stealth mode to hunt humans even without smell, study finds
When smell is gone, heat detection kicks in Live Events Indian scientists find new immune cell type in dengue response Immune memory and the vaccine potential The evolutionary advantage of mosquitoes (You can now subscribe to our (You can now subscribe to our Economic Times WhatsApp channel A new study shows that Aedes aegypti , the mosquito responsible for spreading dengue, yellow fever and Zika, can still find human targets even after losing its sense of smell. At the same time, Indian scientists have identified a specific group of immune cells that could reshape the understanding of how the body responds to dengue at Rockefeller University experimented with Aedes aegypti by disabling its primary olfactory gene, Orco, which helps the mosquito detect human odours. They expected this would impair the mosquito's ability to hunt the mosquito adapted. According to the study published in Science Advances, even without its sense of smell, the mosquito could still locate humans by sensing body heat. The researchers discovered that Orco mutants used their forelegs, not just their antennae, to detect skin was linked to a heat-sensitive receptor called Ir140. When Orco was removed, the mosquito compensated by increasing the activity of Ir140, a process known as upregulation. This kind of sensory compensation is common in humans, such as improved hearing among people with visual impairments. The same pattern in mosquitoes points to how evolution has shaped them into efficient it was only when both Orco and Ir140 were knocked out that Aedes aegypti lost its ability to sense human a separate study, Indian scientists at the National Institute of Immunology (NII) and AIIMS Delhi, along with international collaborators, have identified a key group of immune cells that play a central role during dengue immune cells — a subset of CD4+ T cells — are known as PD-1+CXCR5–CD4+ T cells. They activate B cells, which are responsible for producing antibodies. This process is mediated by a signaling molecule called conventional follicular helper T cells that work within germinal centres of lymph nodes, these newly identified peripheral helper cells operate outside them — in extrafollicular niches — and may even reach inflamed discovery provides new insight into why antibodies behave unpredictably in dengue. Antibodies can protect the body, but in some cases, especially among individuals with past dengue infections, they can worsen the disease through a process known as antibody-dependent enhancement (ADE).The study also found that PD-1+ helper T cells are not uniform. They divide into IL-21-producing helper cells and cytotoxic cells. Some may remain in the body as memory cells, possibly contributing to long-term immune are still trying to determine whether these cells offer protection or increase risk during future dengue infections. If understood better, these cells could help develop targeted vaccines against advancements in science, the mosquito remains one step ahead. Swarnadip Ghosh, a researcher from the National Centre for Biological Sciences (NCBS) in Bengaluru, described the mosquito's ability in verse:'When scent fades out,the mozzie's not beat,She hunts you down bythe stink of your nose? No problem —she's got legs that feel heat,And still thinks yourblood is a five-star treat.'(The article was orignially published in TOI)
Time of India
23-06-2025
- Health
- Time of India
Dengue mosquito is a much smarter predator than thought, it uses a stealth mode to hunt humans even without smell, study finds
A new study shows that Aedes aegypti , the mosquito responsible for spreading dengue, yellow fever and Zika, can still find human targets even after losing its sense of smell. At the same time, Indian scientists have identified a specific group of immune cells that could reshape the understanding of how the body responds to dengue infection. When smell is gone, heat detection kicks in Researchers at Rockefeller University experimented with Aedes aegypti by disabling its primary olfactory gene, Orco, which helps the mosquito detect human odours. They expected this would impair the mosquito's ability to hunt humans. Instead, the mosquito adapted. According to the study published in Science Advances, even without its sense of smell, the mosquito could still locate humans by sensing body heat. The researchers discovered that Orco mutants used their forelegs, not just their antennae, to detect skin temperature. by Taboola by Taboola Sponsored Links Sponsored Links Promoted Links Promoted Links You May Like Buy Brass Idols - Handmade Brass Statues for Home & Gifting Luxeartisanship Buy Now Undo This was linked to a heat-sensitive receptor called Ir140. When Orco was removed, the mosquito compensated by increasing the activity of Ir140, a process known as upregulation. This kind of sensory compensation is common in humans, such as improved hearing among people with visual impairments. The same pattern in mosquitoes points to how evolution has shaped them into efficient hunters. However, it was only when both Orco and Ir140 were knocked out that Aedes aegypti lost its ability to sense human heat. Live Events Indian scientists find new immune cell type in dengue response In a separate study, Indian scientists at the National Institute of Immunology (NII) and AIIMS Delhi, along with international collaborators, have identified a key group of immune cells that play a central role during dengue infection. These immune cells — a subset of CD4+ T cells — are known as PD-1+CXCR5–CD4+ T cells. They activate B cells, which are responsible for producing antibodies. This process is mediated by a signaling molecule called IL-21. Unlike conventional follicular helper T cells that work within germinal centres of lymph nodes, these newly identified peripheral helper cells operate outside them — in extrafollicular niches — and may even reach inflamed tissues. This discovery provides new insight into why antibodies behave unpredictably in dengue. Antibodies can protect the body, but in some cases, especially among individuals with past dengue infections, they can worsen the disease through a process known as antibody-dependent enhancement (ADE). Immune memory and the vaccine potential The study also found that PD-1+ helper T cells are not uniform. They divide into IL-21-producing helper cells and cytotoxic cells. Some may remain in the body as memory cells, possibly contributing to long-term immune response. Researchers are still trying to determine whether these cells offer protection or increase risk during future dengue infections. If understood better, these cells could help develop targeted vaccines against dengue. The evolutionary advantage of mosquitoes Despite advancements in science, the mosquito remains one step ahead. Swarnadip Ghosh, a researcher from the National Centre for Biological Sciences (NCBS) in Bengaluru, described the mosquito's ability in verse: 'When scent fades out, the mozzie's not beat, She hunts you down by the stink of your feet. No nose? No problem — she's got legs that feel heat, And still thinks your blood is a five-star treat.' (The article was orignially published in TOI)
