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.
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.”
From left: Noam Harpaz, MD, Professor of Pathology, and Medicine (Gastroenterology); Sanford J. Grossman, PhD; Judy H. Cho, MD; and Asher A. Kornbluth, MD, Clinical Professor of Medicine (Gastroenterology).
The Sanford J. Grossman Charitable Trust has committed $3 million to a center at the Icahn School of Medicine at Mount Sinai that is focused on advancing the understanding of Crohn’s disease and creating personalized medicine for its treatment.
“Mount Sinai has a large and unique data set on patients: clinical symptoms, pathology reports, genomics, family history, and radiology,” says the founder of the trust, the economist Sanford J. Grossman. “My hope is that the integration and analysis of this data will enable a better understanding of Crohn’s disease, and with that knowledge, therapies will be developed to alter the natural course of the disease.”
Crohn’s is a chronic inflammatory bowel disease that affects nearly 700,000 people in the United States. Over time it can damage the bowel and create complications such as strictures, a narrowing section of the intestine that can lead to loss of function and reduce the quality of a patient’s life.
“Our main goal is to develop treatments that specifically deal with stricture in Crohn’s disease, and that aren’t the usual anti-inflammatory treatments,” says Judy H. Cho, MD, Director of the Center, and the Ward-Coleman Chair in Translational Genetics at the Icahn School of Medicine at Mount Sinai.
One new effort is a small clinical trial led by Robert Hirten, MD, Assistant Professor of Medicine (Gastroenterology) at the Icahn School of Medicine, that is exploring whether steroids are beneficial for Crohn’s patients hospitalized with a bowel obstruction caused by stricturing. Dr. Cho is conducting genetic and molecular projects involving pluripotent stem cells that might someday be engineered to repair the defects that cause Crohn’s disease. She says, “We are very grateful for Dr. Grossman’s donation, which will fund our unique, integrative team and catalyze new research.”
Natalia Leal and her son Gabriel are participants in FAMILIA, which instructs preschoolers and their families on cardiovascular health.
Children may have a better chance of avoiding unhealthy habits linked to obesity and cardiovascular disease later in life if they are taught properly about healthy behaviors in preschool, Mount Sinai researchers have shown in a first-of-its-kind study.
The researchers focused on children living in a socioeconomically disadvantaged community, a situation that is commonly linked to higher rates of obesity, heart disease, and other health issues. Valentin Fuster, MD, PhD, Director of Mount Sinai Heart and Physician-in-Chief of The Mount Sinai Hospital, created and led the trial, called the FAMILIA Project at Mount Sinai Heart. The results were published in the April 22 online issue of Journal of the American College of Cardiology.
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, center; and from left, Scott H. Sicherer, MD, Director of the Elliot and Roslyn Jaffe Food Allergy Institute, Mount Sinai Health System; Prasert Auewarakul, MD, PhD, Deputy Dean of Research, Faculty of Medicine, Siriraj Hospital, Mahidol University; Hugh A. Sampson, MD, Director Emeritus of the Elliot and Roslyn Jaffe Food Allergy Institute; and Pakit Vichyanond, MD, Director, Samitivej Allergy Institute.
The Icahn School of Medicine at Mount Sinai recently agreed to collaborate on food allergy research with the Siriraj Hospital, Mahidol University, and the Samitivej Allergy Institute, prominent medical institutions in Bangkok, Thailand. Initial studies will center on wheat allergies—one of the most common—that appear to be increasing in Thailand. In 2018, researchers from the Elliot and Roslyn Jaffe Food Allergy Institute at the Icahn School of Medicine published the results of a rigorous clinical trial showing that more than half of children in the study were successfully desensitized to wheat after a year of oral immunotherapy.
Study co-authors, from left: Zahi Fayad, PhD, Director of the Translational and Molecular Imaging Institute; and Willem J.M. Mulder, PhD, Professor of Radiology, and Oncological Sciences.
The nearly 35,000 individuals who receive organ transplants each year in the United States face a harsh reality: the immunosuppressive drugs they must take to maintain organ survival also weaken the immune system, breaking down the body’s critical defenses against cancer, infection, and more. Researchers at the Icahn School of Medicine at Mount Sinai recently developed an innovative type of immunotherapy based on nanotechnology that they hope will address this conundrum. Their findings, published in the November 6, 2018, issue of Immunity, have demonstrated the technology’s feasibility of long-term organ acceptance in mice.
“This is a whole new approach to programming the immune system, not just another small molecule drug that’s going to help with organ transplantation,” says Zahi Fayad, PhD, Director of the Icahn School of Medicine at Mount Sinai’s Translational and Molecular Imaging Institute, which conducted the work. Dr. Fayad is also Professor of Diagnostic, Molecular, and Interventional Radiology, and Medicine (Cardiology). “Because of the many problems this approach addresses—the risk of rejection, the shortage of organs for transplant, the cost of these procedures—we believe it can be transformative for the organ transplant field.”
Jordi Ochando, PhD
The immunotherapy works by regulating innate immune memory, or trained immunity, which the investigators found to play a central role in organ rejection. In trained immunity, immune cells known as myeloid cells initiate the body’s immune system response by activating T cells, which then attack the transplanted organ.
“By inhibiting trained immunity, we prevent activation of the myeloid cells and their subsequent activation of T cells,” says Jordi Ochando, PhD, the study’s co-senior author, who is Assistant Professor of Medicine (Nephrology), Oncological Sciences, and Pathology at the Icahn School of Medicine. “This novel technology preserves the normal function of the T cells, which is to protect the body against cancer and infections.”
Identifying trained immunity as a target enabled the Mount Sinai scientists to focus on a signaling pathway known as mammalian target of rapamycin (mTOR), which regulates immune cell metabolism. The team developed an injectable nanoimmunotherapy based on high-density lipoprotein (HDL) nanomaterials and the existing mTOR inhibitor rapamycin.
“These nanomaterials essentially deliver the rapamycin to the myeloid cells, and that changes the metabolic state of the cells and prevents their activation,” says co-senior author Willem J.M. Mulder, PhD, Professor of Radiology, and Oncological Sciences at Icahn School of Medicine, and Director of the Nanomedicine Program. The absence of myeloid cell and T cell activation, Dr. Mulder points out, could drastically reduce the need for transplant patients to take lifelong immunosuppressive medicines to prevent graft rejection.
