Adolfo García-Sastre, PhD, a Leader in the Study of Viruses, Is Elected to the National Academy of Sciences

“This is a great recognition from my peers,” Adolfo García-Sastre, PhD, says, “not just for me, but for the achievements of all past and present members of my laboratory.”

Adolfo García-Sastre, PhD, Director of the Global Health and Emerging Pathogens Institute, and the Irene and Dr. Arthur M. Fishberg Professor of Microbiology, and Medicine (Infectious Diseases) at the Icahn School of Medicine at Mount Sinai, has been elected to the National Academy of Sciences.

The honor recognizes Dr. García-Sastre’s outstanding contributions to his field, which include developing reverse genetics techniques that revealed the molecular basis of the influenza virus, led to the recreation of the extinct pandemic influenza virus of 1918, and paved the way for improved influenza virus vaccines. His laboratory also defined the role of influenza nonstructural protein 1 (NS1) in dampening the body’s immune response. Dr. García-Sastre says his laboratory’s overarching goal is “to better understand how viruses cause disease, leading to improved prophylactic and therapeutic interventions.” It is working on a universal influenza vaccine that does not require yearly modifications, and on viral therapeutics that target cancerous tumors but do not affect healthy cells.

“Dr. García-Sastre’s research represents the frontier of his field,” says Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, and President for Academic Affairs, Mount Sinai Health System. “The discoveries made by him and others at Mount Sinai will result in powerful new means to combat deadly viruses that affect millions of people and lay the groundwork for discovery of viruses yet unknown.”

Mount Sinai now has three faculty members in the National Academy of Sciences: Dr. García-Sastre; Maria Iandolo New, MD, Professor of Pediatrics, Medicine (Endocrinology), and Genetic and Genomic Sciences; and Peter Palese, PhD, Horace W. Goldsmith Professor and Chair of Microbiology, and Professor of Medicine (Infectious Diseases).

“This is a great recognition from my peers,” Dr. García-Sastre says, “not just for me, but for the achievements of all past and present members of my laboratory.”

Mount Sinai Renames Department of Neuroscience

From left, Paul J. Kenny, PhD; Eric J. Nestler, MD, PhD; benefactors Pamela Nash, Helen Nash, Beth Nash, and Joshua Nash, member, Mount Sinai Boards of Trustees; and Richard A. Friedman, Co-Chairman, Boards of Trustees.

It has been a time of outstanding achievement for the Icahn School of Medicine at Mount Sinai’s Department of Neuroscience—worthy of a celebration.

On Wednesday, May 8, Mount Sinai leadership, benefactors, faculty, and staff attended a reception at the Hess Center for Science and Medicine to unveil the Department’s renaming to the Nash Family Department of Neuroscience, an event held to honor the Nash family for their philanthropic generosity and extraordinary commitment to brain research.

“The Nash family has been supporting critical initiatives at Mount Sinai for more than 40 years and began a focused commitment to advance our neuroscience community more than a decade ago,” says Eric J. Nestler, MD, PhD, Nash Family Professor of Neuroscience, Director of The Friedman Brain Institute, and Dean for Academic and Scientific Affairs at the Icahn School of Medicine at Mount Sinai. “The research that has been made possible through the family’s generosity is being translated into fundamentally new and improved treatments for some of the world’s most devastating brain disorders. We are forever grateful for their commitment to this important work.”

Richard A. Friedman with guests at the reception. A substantial gift from the Friedman family allowed for the creation of The Friedman Brain Institute.

As a direct result of the Nash family’s support, Mount Sinai’s neuroscience program has seen unprecedented growth. Over the past decade, more than 40 basic neuroscience faculty have been recruited to Mount Sinai. Today, the Neuroscience department is ranked No. 1 in the nation among U.S. medical schools in National Institutes of Health (NIH) funding.

“This is testament to the incredible research environment we have created at Mount Sinai with the support of the Nash family,” says Paul J. Kenny, PhD, the Ward-Coleman Professor and Chair of the Department, and Director of Mount Sinai’s Drug Discovery Institute, who has made significant contributions to furthering the understanding of the neurobiological mechanisms of drug addiction and obesity. “With their tremendous support, we have built the depth and breadth of scientific expertise that is required for us to have a real impact in many key areas of brain research. We are translationally focused, so our work is highly relevant to human health and central nervous system disorders. We are also a very close community and we support all of our colleagues, particularly our junior scientists. We foster an environment of research excellence but also one of collaboration and support. As a result, we are second to none when it comes to research funding and scientific impact.”

Helen S. Mayberg, MD, left, with Helen Nash

Groundbreaking work in deep brain stimulation is being conducted in the newly established Nash Family Center for Advanced Circuit Therapeutics, whose founding Director, Helen S. Mayberg, MD, Mount Sinai Professor in Neurotherapeutics, and Professor of Neuroscience, Neurology, Psychiatry, and Neurosurgery, is a pioneer in using brain circuit information to treat neuropsychiatric disorders. She is leading a team to harness the potential of deep brain stimulation—an innovative surgical procedure that has proven successful in treating movement disorders—to address a range of conditions that include depression, addiction, and schizophrenia.

“Additionally, we have researchers who have deep expertise in the mechanisms of gene regulation, and those with demonstrated ability to functionally dissect, manipulate, and understand brain circuitry in the context of complex behaviors,” Dr. Kenny says. “That is where research funding is increasingly directed, and we are on the cutting edge of neurocircuitry research.”

The goal now, Dr. Kenny adds, is to bring together the Department’s key strengths in brain circuitries and mechanisms of gene expression to drive new discoveries related to brain function and its role in disease. “Given the outstanding quality of research in our Department, and the level of NIH funding we have successfully competed for, I believe Mount Sinai is positioned to have a profound impact on human brain health.”

 

Eric J. Nestler, MD, PhD, welcomed guests and spoke about the strengths of the Nash Family Department of Neuroscience.

Research Uncovers How Serotonin in the Nucleus Can Regulate Gene Expression Within Brain Cells

Lorna Farrelly, PhD, and Ian Maze, PhD

Serotonin, a powerful chemical that sends signals between nerve cells in the brain, has long been thought to play a key role in processes such as appetite, mood, and sleep. Now, research by neuroscientists at the Icahn School of Medicine at Mount Sinai suggests that the molecule can also enter the nucleus of these cells and help turn genes on. It is a surprising discovery that has the promise to yield fundamental new knowledge about addiction, mood disorders, and neurodegenerative diseases such as Parkinson’s disease.

The findings, which were recently published in the journal Nature, are a divergence from conventional thinking that neurotransmitters have one role—which is to bind to nerve cells and send signals that change these cells’ activity.

“We have shown that there is a novel role for neurotransmitters in the brain that is independent of neurotransmission, but critically important to their overall signaling,” says Ian Maze, PhD, Assistant Professor of Neuroscience, and Pharmacological Sciences, and senior author of the multicenter study. “It suggests that our current understanding of these molecules is incomplete and requires further investigation.” Study authors also included postdoctoral fellow Lorna Farrelly, PhD.

The study involved DNA, the blueprint for all cell functions in the body. Each cell contains two strands of DNA that are packaged by histone proteins and arranged in spools known as nucleosomes. The tighter the DNA is wound into nucleosomes, the less likely that genes being encoded will be turned on, or expressed; when it is not wound as tightly, genes are more likely to be expressed.

Based on previous research that had found large pools of neurotransmitters in the nucleus of neurons and suspecting that this could result in additional, neurotransmission-independent functions for these chemicals, Dr. Maze and his team hypothesized that certain nuclear proteins may be modified by these molecules to affect their functions. They discovered that a protein, tissue Transglutaminase 2, can directly attach serotonin molecules to histone proteins, a process called histone serotonylation. Once the serotonin is attached, stronger expression of genes associated with these modified histones is observed.

They also demonstrated that these serotonyl marks on the histone protein help draw other proteins that play a key role in increasing gene expression. “We found that these marks hyper-recruit one particular factor, Transcription factor II D, that enables the genes to turn on,” Dr. Maze says. “That provides some mechanistic insight into how these marks may be influencing gene expression.”

In a blog entry summarizing these findings, Francis S. Collins, MD, PhD, the Director of the National Institutes of Health, wrote, “While much more study is needed, this is a potentially groundbreaking discovery. Not only could it have implications for managing depression and other mood disorders, it may also open new avenues for treating substance abuse and neurodegenerative diseases.”

 

Joining Forces to Create a New Digital Health Institute

From left: Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, and President for Academic Affairs, Mount Sinai Health System; and Christoph Meinel, PhD, Chief Executive Officer, Hasso Plattner Institute, and Dean, Joint Digital Engineering Faculty, Hasso Plattner Institute and University of Potsdam.

The Mount Sinai Health System and the Hasso Plattner Institute (HPI), a leading data science research and educational institution in Germany, have formed an affiliation that will combine their expertise in health care delivery, biomedical and digital engineering, and artificial intelligence. The aim is to develop digital health tools with real-time predictive and preventive capabilities that empower patients and health care providers and improve health outcomes.

Erwin P. Bottinger, MD, left, and Joel Dudley, PhD, are co-directors of the new Hasso Plattner Institute for Digital Health at Mount Sinai.

The newly formed Hasso Plattner Institute for Digital Health at Mount Sinai will be led by Joel Dudley, PhD, Executive Vice President for Precision Health, Mount Sinai Health System, Mount Sinai Professor in Biomedical Data Science, and Director of the Institute for Next Generation Healthcare, Icahn School of Medicine at Mount Sinai; and Erwin P. Bottinger, MD, Professor of Digital Health-Personalized Medicine, Hasso Plattner Institute, University of Potsdam, Germany, and Head of HPI’s Digital Health Center. A $15 million gift from the Hasso Plattner Foundation will establish the new Institute, which was announced in March at the Icahn School of Medicine.

“This endeavor will usher in a new era of digital health at Mount Sinai that advances the field of precision medicine,” says Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, and President for Academic Affairs, Mount Sinai Health System. “By leveraging our shared knowledge and academic excellence, Mount Sinai and HPI are positioned to find solutions that will revolutionize health care and science, and improve health nationally and globally.”

The Hasso Plattner Institute for Digital Health at Mount Sinai joins more than 20 institutes launched at the Icahn School of Medicine. Its goals include building a digital health population of engaged participants to collect comprehensive and longitudinal health data from wearable devices, genetic sequencing, and electronic health records; creating a cloud-based health data platform for research and care using machine learning and artificial intelligence; and researching and testing prototype digital health solutions for patients, providers, and health systems. Mount Sinai’s expertise in genomics, big data, supercomputing, and bioinformatics—along with a large and diverse patient population and an ability to translate from the lab directly to the clinic—provides a foundation for the Institute.

For example, the Institute for Next Generation Healthcare (INGH), under the leadership of Dr. Dudley, has developed a translational biomedical research model using advances in clinical medicine, digital health, and artificial intelligence, and INGH’s Lab 100 is leveraging data and technology to redesign the way health is measured and health care is delivered. In another innovative effort, the BioMe™ BioBank Program, housed at The Charles Bronfman Institute for Personalized Medicine at Mount Sinai, is enabling researchers to conduct genetic, epidemiologic, molecular, and genomic studies on large collections of research specimens linked with electronic health records. Until 2015, Dr. Bottinger was Professor of Medicine (Nephrology), and Pharmacological Sciences at the Icahn School of Medicine, and he helped lay the groundwork for the BioBank Program and The Institute for Personalized Medicine.

“Investigators at the Icahn School of Medicine at Mount Sinai and the Hasso Plattner Institute have been publishing groundbreaking work in the areas of genome diagnostics, precision medicine, digital health, biomedical data science, artificial intelligence, and information technology,” says Dr. Dudley. “We believe the new Institute will help turn the promise of digital health into reality at the front lines of next generation health care.”

Dr. Bottinger says, “We know we can save lives, prevent disease, and improve the health of patients with artificial intelligence in real-time analysis of health data from electronic health records, genetic information, and mobile sensor technologies.”

Electronic Lab Notebook for Researchers at the Icahn School of Medicine at Mount Sinai


The Icahn School of Medicine at Mount Sinai now provides an Electronic Lab Notebook service for all researchers through an enterprise license agreement with LabArchives. The service is a secure, cloud-based software designed to replace paper notebooks and to help improve designing and documenting experiments.

“Mount Sinai is moving into the digital age of research record-keeping, and we really need folks to embrace it, to try it out,” says Reginald Miller, DVM, Dean, Research Operations and Infrastructure. “It’s a great way to collaborate with your colleagues, both internally and externally. It’s a resource that has unlimited user capability, and it’s free.”

At a time when science is being encouraged to be more reproducible and rigorous, this type of electronic note keeping is important in being able to show the data to those who request it and to be able to transmit and disseminate the data, according to Talia Swartz, MD, PhD, Assistant Professor, Division of Infectious Diseases.

“This has a huge advantage in providing a platform to make that readily available, and that is of interest to anyone who is trying to disseminate their data and collect it for the purpose of rigorous science,” says Dr. Swartz.

Neanderthal Teeth Yield Insights Into Past and Present

Manish Arora, PhD, MPH; and Christine Austin, PhD

Neanderthals became extinct more than 20,000 years ago, but an innovative study of teeth by an international team, including researchers at the Icahn School of Medicine at Mount Sinai, has uncovered details about their lives that may lead to new insights into human evolution and into chemical exposures that affect health outcomes now.

The study is the first to use teeth to explore in weekly increments the relationship between ancient climate change and the development of hominins—humans and their immediate ancestors. Researchers examined remains recovered from Payre, an archaeological site in the Rhone Valley of Southeastern France, analyzing one tooth each from two Neanderthal children who lived 250,000 years ago, and another tooth from a “modern” human child who lived 5,000 years ago.

“Much like trees, teeth have growth rings that enable us to look at what happened in the life of an individual on a weekly basis,” says co-author Christine Austin, PhD, Assistant Professor of Environmental Medicine and Public Health, Icahn School of Medicine. “For these teeth, we cut a sample approximately 100 microns thick, or the width of a human hair, removed a small amount of material from the surface of the growth rings using a laser, analyzed the elements in that material using inductively coupled plasma mass spectrometry, and then constructed a timeline of exposure to the elements for each individual.”

Analyzing a slice of a Neanderthal child’s tooth, 100 microns thick, provided a timeline of development and chemical exposures. For example, a “stress line” around day 707 of the child’s life indicated a period of severe illness or hunger.

This technology was developed by Manish Arora, PhD, MPH, the Edith J. Baerwald Professor of Environmental Medicine and Public Health, Icahn School of Medicine, and senior author of the study, which was published in Science Advances in October 2018. “Dr. Austin’s work is a game changer for the way we analyze archaeological samples and for our understanding of how environmental stressors have impacted the evolution of modern humans and how they continue to impact our health,” Dr. Arora says. “Her work on the evolution of breastfeeding has direct relevance to understanding the benefits of breast milk in modern medical practice.”

Dr. Austin and her colleagues at institutions in France and Australia noted developmental deformations in the Neanderthal teeth that reflected the stresses of life during harshly cold winters. In addition, both Neanderthals were exposed to lead at least twice during late winter or early spring. Dr. Austin says two mines are located within foraging distance of the recovery site, indicating that food and water from the area may have been contaminated with lead. There were also signs of high, acute exposure, which could have resulted from an event such as inhalation of a cave fire.

“Previously, we thought that lead exposure mainly happened post-industrialization,” Dr. Austin says. “Now we see that is not the case, and that raises questions about the impact of this neurotoxin on their neurodevelopment and ultimately their behavior. That is something we want to explore further.”

Equally of interest were the findings related to breastfeeding. One of the Neanderthals was weaned at about two and a half years of age, which is similar to the norm for early humans. “Compared to other primates, humans wean early, which enables higher reproductive rates and is likely one of the reasons for our species’ success,” Dr. Austin says. “Seeing a human-like weaning pattern in Neanderthals is very interesting and raises questions about when this nursing behavior evolved.”

Dr. Austin says the study could also lead to insights into chemical exposures from breast milk that could impact lifelong health. “There is a growing body of data on the importance of breast milk in the development of an infant’s microbiome,” she says. “By better understanding how the composition of breast milk has evolved, in addition to breastfeeding practices, we can start to propose interventions at critical developmental windows that mitigate exposure to environmental stresses and toxins and thus improve health outcomes.”     

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