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Mount Sinai Awarded Nearly $7 Million From National Institutes of Health to Create New York Coalition to Recruit for Highly Diverse Health Database 
Health System to serve as a lead site for the All of Us research program

(New York, NY – November 11, 2024) – The Mount Sinai Health System has been awarded nearly $7 million from the National Institutes of Health (NIH) to create and lead a New York coalition to contribute to one of the most diverse health databases in history, ultimately informing and guiding individualized treatment and care for a variety of diseases and health conditions. Mount Sinai will also work to increase the number of participants from various demographics, regions, and stages of opioid use disorder to address the public health crisis of rising overdose deaths.

The New York coalition will include academic medical centers and community partners with expertise in engaging, recruiting, and retaining participants often underrepresented in biomedical research in New York City—one of the most ethnically and culturally diverse enclaves in the world. Along with Mount Sinai, the group of collaborators includes Weill Cornell Medicine, New York City Health + Hospitals, the Institute for Family Health, and NYU Langone. The New York coalition will try to recruit more than 7,000 new participants across the tri-state area to join the NIH’s All of Us Research Program in the first year.

“This multi-institutional effort will fill a gap to significantly increase recruitment of participants in an area of the country with rich diversity,” said Principal Investigator Monica Kraft, MD, the Murray M. Rosenberg Professor of Medicine and Chair of the Department of Medicine at Mount Sinai Health System and the Icahn School of Medicine at Mount Sinai. “Our partnership encompasses dozens of hospitals and medical practices, longstanding collaborations, senior research investigators, and seasoned staff with experience in recruiting diverse populations. We will work closely with the All of Us consortium and key stakeholders, assess the impact of our activities, identify best practices, and share both our expertise and discoveries along the way. We look forward to continuing to build on our strong and robust IT, data science, clinical, data collection, and electronic health record infrastructures.”

The coalition will join the other All of Us regional hubs to also enroll 3,300 new participants with opioid use disorder, an epidemic that has affected thousands across the United States through increasing opioid use, addiction, and overdose deaths. The crisis has most recently involved a rise of synthetic opioids like fentanyl, which are significantly more potent and deadly than heroin and prescription opioids. There are distinct racial disparities among those with opioid use disorder, according to the Centers for Disease Control and Prevention: although opioid use is more common among white Americans, Black adults and teens experienced a steeper increase in the rate of fatal opioid overdoses than whites during the last decade.

Three Icahn Mount Sinai leaders join Dr. Kraft as Principal Investigators for the New York coalition: Bruce D. Gelb, MD, Dean for Child Health Research, the Gogel Family Professor and Director of The Mindich Child Health and Development Institute, and Director of the Center for Molecular Cardiology; Carol R. Horowitz, MD, MPH, Dean for Gender Equity in Science and Medicine, Director of the Institute for Health Equity Research, and Professor of Medicine, and Population Health Science and Policy; and Girish N. Nadkarni, MD, MPH, Irene and Dr. Arthur M. Fishberg Professor of Medicine, Director of The Charles Bronfman Institute of Personalized Medicine, and System Chief of the Division of Data-Driven and Digital Medicine.

“Our participation in the All of Us Research Program is a significant step towards revolutionizing health care through the power of multimodal data,” said Dr. Nadkarni. “This grant will enable us to harness cutting-edge technologies and integrate vast amounts of health information to uncover new insights and accelerate the development of personalized treatments. The world can leverage this comprehensive dataset to identify novel biomarkers, predict disease progression, and ultimately enhance clinical outcomes.”

Dr. Horowitz added: “Mount Sinai has a longstanding and deep commitment to health equity. Working in close partnership with expert clinicians, patients, and community advocates, we will ensure that our New York neighbors from more disadvantaged backgrounds and who have experienced health disparities are among the first to benefit from the advances in science and medicine that stem from All of Us.”

The investigators will harness insights from trusted networks and communities of ongoing research they currently lead, including The Charles Bronfman Institute for Personalized Medicine’s BioMe BioBank program, which supports rapid analysis from electronic medical information; the Mount Sinai Million Health Discoveries Program, which aims to carry out genetic sequencing of 1 million Mount Sinai patients within the next five years; and the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, which is examining the long-term effects of COVID-19.

The All of Us Research Program was created in 2015 to reflect the diversity of the United States and its territories, with a focus on precision medicine, or development of individualized plans for disease prevention and treatment. The national effort includes gathering data from 1 million or more diverse people, including those who are LGBTQ+ or Indigenous, with the goal of accelerating medical research and health breakthroughs. The comprehensive dataset is housed on a secure cloud-based platform and participating researchers can access information from surveys, genomic analyses, electronic health records, physical measurements, and wearables to study a range of factors that influence health and disease, including the environment, lifestyle, and genes. To date, more than 800,000 people have enrolled in the program.

About the Mount Sinai Health System

Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across eight hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.

Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report’s® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2024-2025.

For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.

Newswise — University of California San Diego School of Medicine has received a five-year, $8 million grant from the National Institute on Drug Abuse (NIDA) to study the genetics of substance use disorders. The grant will support a NIDA P30 Core Center of Excellence, which ultimately aims to understand why some people are more susceptible to addiction than others. This knowledge will be instrumental in developing more personalized and effective treatments to address the public health crisis posed by substance use disorders, which affect tens of millions of Americans at an enormous cost to the U.S. economy.

Some people who drink alcohol or try illicit substances become addicted to these drugs, but most do not, according to principal investigator Abraham Palmer, Ph.D., professor and vice chair for basic research in the School of Medicine’s Department of Psychiatry.

“And that vulnerability is partially genetic,” said Palmer. “We’re very interested to know: what are the genetic differences between people who develop substance use disorders and those who do not?”

The P30 center uses heterogeneous stock (HS) rats as a model organism to address this question because, like humans, they display individual differences in drug-seeking behaviors and their genomes lend themselves to genotype-phenotype association studies. They also share many of the same genes that control reward pathways in the brain thought to be important in substance use disorders. The center will build upon 10 years of NIDA-supported research mapping the relationship between HS rat genotypes and these complex behavioral traits.

“We have an enormous database of both the behavior of the animals and of the genetic characteristics of those animals,” said Palmer. “And that allows us to look at the relationship between the genotype of an animal and its phenotype to understand which important genetic differences shape certain behaviors.”

Research by Palmer, Francesca Telese, Ph.D., associate professor of psychiatry, and colleagues used single nucleus RNA sequencing to compare gene expression of individual brain cells in the amygdalas of HS rats who sought large amounts of cocaine versus those who abstained. The amygdala is an area of the brain found in all mammals, including humans, and it plays a central role in addiction.

“By looking at these single nuclei, we were able to see lots of differences that persist weeks after the drug has gone away,” said Palmer.

One of the strongest patterns was a difference in genes related to oxidative stress, which affects cellular energy metabolism. The brain cells of the cocaine-preferring rats also showed increased GABAergic signaling, which regulates cognition, emotion and motivation. In addition, these rats engaged in relapse-like behavior.

“Our results suggested to us that vulnerability to cocaine addiction affects the way cells produce and use energy,” said Telese.

Glyoxalase 1 (also known as Glo1) is a gene that codes for an enzyme which mediates the relationship between oxidative stress and energy metabolism. The researchers found that inhibiting the enzyme’s activity using a molecule called pBBG reversed the drug-seeking behavior of rats who had previously shown a preference for cocaine.

“Those animals dramatically reduced the amount of cocaine that they took, whereas the normal animals didn’t show any response to the drug,” said Palmer. “It’s as if the drug is specifically doing something in these vulnerable individuals.”

Based on these findings, the researchers believe Glo1 could be a promising target for the development of new therapeutic compounds to treat substance use disorders in humans. And Glo1 is just one of many genes the center is investigating as potential drug targets. With the costs of addiction to individuals and society so high, better treatment options are sorely needed.

The center supports a growing national and international community of researchers studying the genes behind substance use disorders. It conducts genome-wide association studies and maintains and distributes data from its vast repository of genotype-behavioral phenotype relationships to other investigators. Its comprehensive database allows the center to provide researchers with drug-naive HS rats at predictably high and low genetic risk for drug abuse, which make them a particularly good model for studying human addiction.

To foster innovation and support workforce development, the center also provides grants and services to early-stage investigators for pilot studies. In addition, it offers immersive research opportunities for high school and undergraduate students in the laboratories affiliated with the center. Research supported by the center could lead to new treatments for other psychiatric disorders as well.

Additional principal investigators (PIs) on the project include Oksana Polesskaya, Ph.D., in the Department of Psychiatry at UC San Diego, Leah Solberg Woods, Ph.D., professor of physiology and pharmacology at Wake Forest University, and Pejman Mohammadi, Ph.D., associate professor at the Seattle Children’s Research Institute and the Department of Genome Sciences at University of Washington School of Medicine.

The title of the grant, awarded by the National Institute on Drug Abuse, is “Center for Genetics, Genomics, and Epigenetics of Substance Use Disorders in Outbred Rats” (P30DA060810).

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Newswise — Cardiovascular disease remains a top cause of sickness and death in the U.S. and worldwide. Doctors and researchers have it especially high on their radar because it’s more modifiable and preventable than many other diseases and causes of death.

Importantly, though, modification and prevention rely on early detection and mitigation of risk factors like hypertension and high cholesterol. Unfortunately, detection and mitigation are suboptimal throughout the U.S. population: Experts estimate that up to 75% of young adults who have risk factors such as hypertension and high cholesterol are unaware of their conditions.

A recent study led by researchers at the University of Chicago found that boys and men who enact behaviors more closely aligned with stereotypical gender norms in their social environment are less likely to report receiving diagnoses or treatment for cardiovascular disease risk factors. Their findings build on existing research showing that sociocultural pressures to perform male gender identity are linked to detrimental health-related behaviors, such as substance use and rejection of medical therapies and recommendations.

“It’s well known that male gender and male sex are associated with lower help-seeking for a range of health conditions — especially mental health and primary care. But previous studies haven’t probed further into the social processes through which male gender is iteratively created through an interplay between the individual and their surroundings,” said Nathaniel Glasser, MD, a general internist and pediatrician at UChicago Medicine and lead author on the paper. “In this new paper, we used innovative measurement techniques to look at the construction of male gender and how it’s associated with cardiovascular disease prevention.”

Glasser and his colleagues analyzed data from Add Health, a nationally representative, longitudinal study that collected health measurements and survey responses from more than 12,300 people at multiple points over the course of 24 years (1994-2018). They quantified Add Health participants’ male gender expressivity by identifying a subset of survey questions that were answered most differently by self-identified male versus female participants, then measuring how closely male participants’ answers to those questions matched those of their same-gendered peers.

“When we talk about gender expression, we’re not looking at anything physiologic that could be affected by the Y chromosome,” Glasser pointed out. “We’re purely focused on self-reported behaviors, preferences and beliefs, and how closely these reported behaviors and attitudes resemble those of same-gendered peers.”

Zeroing in on cardiovascular disease, the researchers compared the Add Health biological measurements with health-related survey responses to see if men with detectable risk factors like high blood pressure reported receiving diagnoses or treatment for those conditions. They found that men who showed more stereotypical gender expression were significantly less likely to report that a healthcare professional had ever told them about certain cardiovascular disease risk conditions. Even when these men did report having previously received a diagnosis, they were still less likely to report that they were taking medication to treat these conditions.

The risk factors examined in the study are all conditions that would normally be detected by screenings that are part of basic primary care. It’s unclear whether the decrease in reported diagnosis and treatment among those with higher male gender expression indicates that men aren’t going in to get screened; that they aren’t paying attention to their diagnoses even when they do get screened; or that they are simply downplaying their diagnoses when asked about them. Whatever the underlying reason, the findings highlight a missed opportunity to prevent or alleviate serious cardiovascular conditions later in life.

“Our hypothesis is that social pressures are leading to behavioral differences that impact cardiovascular risk mitigation efforts, which is concerning because it could be leading to worse long-term health outcomes,” Glasser said.

Ultimately, the authors see the implications of this research reaching far beyond the topic of traditional masculinity.

“We’re seeing how pressures to convey identity — whether it’s rooted in gender, race, sexuality or something else — impact health behaviors,” Glasser said. “Fitting in and achieving belonging is a complicated task, and we feel strongly that increased societal sympathy, empathy and patience for others undertaking that task would be good for people’s health.”

“Male Gender Expressivity and Diagnosis and Treatment of Cardiovascular Disease Risks in Men” was published in JAMA Network Open in October 2024. Authors include Nathaniel Glasser, Jacob Jameson, Elbert Huang, Ian Kronish, Stacy Tessler Lindau, Monica Peek, Elizabeth Tung and Harold Pollack.

WASHINGTON—A new Scientific Statement released today by the Endocrine Society highlights research gaps associated with the negative effects of opioid use on the endocrine system.

The use and misuse of opioids are a growing global problem. Opioids are used to treat pain in people with cancer or other conditions (e.g., after an injury or surgery), however, they are highly addictive and people can develop opioid use disorder (OUD). The World Health Organization estimates 125,000 people died of opioid overdose in 2019.

The use and misuse of opioids has a negative effect on our hormones and can lead to reproductive, bone and adrenal health complications.

“Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement,” reviews data related to the use and misuse of opioids and the effects of these drugs on the endocrine system. The Statement discusses recent research on the clinical consequences of opioids, especially on the hypothalamic-pituitary system and bone health.

“We address the many research gaps associated with the effects and clinical consequences of opioids on the endocrine system within this Scientific Statement,” said lead Statement author Niki Karavitaki, M.Sc., Ph.D., F.R.C.P., of the University of Birmingham, Birmingham Health Partners, and the University Hospitals Birmingham National Health Service Foundation Trust in Birmingham, U.K. “We hope bringing attention to recent research in the space, including opioid use’s impact on gonadal, bone and adrenal conditions, will improve the endocrine health of people using or misusing opioids worldwide.”

The Statement reviews research related to the impact of opioids on gonadal and adrenal function, and bone health. The authors report male hypogonadism, a reproductive health condition that causes low testosterone, as a well-recognized side effect of opioids, and provide more clarity around the drug’s lesser-known effects on other parts of the hypothalamic-pituitary system and bone health. They discuss the link between opioids and the development of hyperprolactinemia and how more research is needed to understand their effect on secondary adrenal insufficiency. 

The Statement authors also assessed how opioids affect the secretion of certain hormones to better understand the connection between opioid use and endocrine disease. These hormones include growth hormone, arginine vasopressin (regulates the body’s water balance), and oxytocin (plays a crucial role in the childbirth process).

They also reviewed research into opioid’s actions on bone metabolism and their negative impact on bone mineral density and risk of fracture.

“Clinicians need to be aware of these endocrine health consequences and monitor patients who are using opioids more closely for signs and symptoms of them,” Karavitaki said.

Other statement authors are Jeffrey Bettinger of Saratoga Hospital Medical Group in Saratoga Springs, N.Y.; Nienke Biermasz of Leiden University Medical Center in Leiden, The Netherlands; Mirjam Christ-Crain of the University Hospital Basel and the University of Basel in Basel, Switzerland; Monica Gadelha of the Universidade Federal do Rio de Janeiro in Rio de Janeiro, Brazil; Warrick Inder of Princess Alexandra Hospital, Brisbane, and the University of Queensland, Brisbane, in Queensland, Australia; Elena Tsourdi of Technische Universität Dresden in Dresden, Germany; Sarah Wakeman of Massachusetts General Hospital, Mass General Brigham and Harvard Medical School in Boston, Mass.; and Maria Zatelli of the University of Ferrara in Ferrara, Italy.

The statement, “Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement,” was published online in the Society’s journal, Endocrine Reviews.

The Endocrine Society develops Scientific Statements to explore the scientific basis of hormone-related conditions and disease, discuss how this knowledge can be applied in practice, and identify areas that require additional research. Topics are selected on the basis of their emerging scientific impact. Scientific Statements are developed by a Task Force of experts appointed by the Endocrine Society, with internal review by the relevant Society committees and expert external reviewers prior to a comment period open to all members of the Society.

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Endocrinologists are at the core of solving the most pressing health problems of our time, from diabetes and obesity to infertility, bone health, and hormone-related cancers. The Endocrine Society is the world’s oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions.

The Society has more than 18,000 members, including scientists, physicians, educators, nurses and students in 122 countries. To learn more about the Society and the field of endocrinology, visit our site at www.endocrine.org. Follow us on Twitter at @TheEndoSociety and @EndoMedia.

BYLINE: Marta Wegorzewska

Newswise — The opioid epidemic claims more 70,000 lives each year in the U.S., and lifesaving interventions are urgently needed. Although naloxone, sold as an over-the-counter nasal spray or injectable, saves lives by quickly restoring normal breathing during an overdose, administrating the medication requires a knowledgeable bystander ­– limiting its lifesaving potential.

A team from Washington University School of Medicine in St. Louis and Northwestern University in Chicago has developed a device that may rescue people from overdose without bystander help. In animal studies, the researchers found that the implantable device detects an overdose, rapidly delivers naloxone to prevent death and can alert emergency first responders.

The findings are available Oct. 23 in Science Advances.

“Naloxone has saved many lives,” said Robert W. Gereau, PhD, the Dr. Seymour and Rose T. Brown Professor of Anesthesiology and director of the WashU Medicine Pain Center. “But during an overdose, people are often alone and unable to realize they are overdosing. If someone else is present, they need access to naloxone — also known as Narcan — and need to know how to use it within minutes. We identified an opportunity to save more lives by developing a device that quickly administers naloxone to at-risk individuals without human intervention.”

Prescription opioids – such as oxycodone – have helped people manage the physical and mental challenges of daily debilitating pain. But the addictive properties of painkillers can lead to their misuse and abuse, which are among the driving forces behind the opioid epidemic. In addition, cheap and easy-to-access synthetic drugs – fentanyl, for example – have flooded the illicit market. Such ultrapotent drugs have accelerated the rise in overdose deaths in the U.S. and were responsible for roughly 70% of such deaths in 2023.

The researchers worked with experts in engineering and material sciences led by John A. Rogers, PhD, a professor of materials science and engineering, biomedical engineering and neurological surgery at Northwestern University, to develop a device ­– the Naloximeter – that uses a drop in oxygen levels as a signal for a potential overdose. Overdosing on opioids leads to slow and shallow breathing. Minutes after the drugs begin to impact respiratory function, breathing stops. Implanted under the skin, the Naloximeter senses oxygen in the surrounding tissues, sending a warning notification to a mobile application if the levels drop below a threshold. If the user doesn’t abort the rescue process within 30 seconds, the device releases stored naloxone.

Implanted under the skin, the Naloximeter, developed by researchers at WashU Medicine and Northwestern University, senses dropping oxygen in the surrounding tissues and sends a warning notification to a mobile application. If the user doesn’t engage with the warning message within 30 seconds, the device releases stored naloxone and can send an alert to first responders.

The researchers implanted the device in the neck, chest or back of small and large animals. The device detected signs of overdose within a minute of dropping oxygen levels, and all animals fully recovered within five minutes of receiving naloxone from the devices.

Naloxone displaces harmful opioids from receptors on the surface of brain cells, altering the cells’ activity. But the drug doesn’t stick around; when the opioids reoccupy and reactivate the receptors, overdose symptoms can return. To provide additional support, the device relays an emergency alert to first responders.

“An additional benefit of calling first responders is that it helps people re-engage with health-care providers,” said Jose Moron-Concepcion, PhD, the Henry E. Mallinckrodt Professor of Anesthesiology at WashU Medicine and an author on the study. “We want to save people from dying from an overdose and also reduce harm from opioids by helping people access the resources and treatments to prevent future overdoses from occurring.”

The researchers were awarded a patent – with some help from the Office of Technology Management at WashU – to protect the intellectual property of the device.

“The Naloximeter is a proof-of-concept platform that isn’t limited to the opioid crisis,” said Joanna Ciatti, a graduate student in Rogers’ lab. “This technology has far-reaching implications for those threatened by other emergent medical conditions such as anaphylaxis or epilepsy. Our study lays important groundwork for future clinical translation. We hope others in the field can build off of these findings to help make autonomous rescue devices a reality.”