In Huffington Post’s new video series “Experimenters,” data scientist Eric Schadt, PhD, founding director of the Icahn Institute for Genomics and Multiscale Biology, discusses his mission to revolutionize health care.
As President Donald Trump and Congressional Republicans contemplate whether to replace, overhaul or modify the Affordable Care Act, it is essential that our leaders exercise caution as they consider the implications of changes to the Medicaid program.
From left: Gary C. Butts, MD; Robert A. Levinson, husband of the late Patricia S. Levinson; and Kenneth L. Davis, MD
More than 100 friends and members of the Mount Sinai Health System paid tribute to the late Patricia S. Levinson at a ceremony in November, when Mount Sinai’s Center for Multicultural and Community Affairs (CMCA) was renamed in her honor.
Mrs. Levinson, a Mount Sinai Trustee for 34 years, “was CMCA’s most passionate advocate,” said Kenneth L. Davis, MD, President and Chief Executive Officer of the Mount Sinai Health System, who spoke at the event. “Her advice, counsel, and generosity were legendary, and she was a tremendous ally and resource for the Health System.”
The sarcophagus of a 3,500-year-old mummy was opened at the Egyptian Museum in Cairo.
At the intersection of medicine, archaeology, and the plot of an Indiana Jones movie lies a course of study pursued by Jagat Narula, MD, PhD, MACC.
Dr. Narula’s highly eminent day jobs include serving as the Chief of Cardiology at Mount Sinai St. Luke’s and Mount Sinai West; Director of Cardiovascular Imaging for the Mount Sinai Health System; Philip J. and Harriet L. Goodhart Professor of Medicine, Icahn School of Medicine at Mount Sinai; and Editor-in-Chief of The Journal of the American College of Cardiology: Cardiovascular Imaging. But for more than six years, he has also traveled the world studying mummies with the Horus Group, named for the Egyptian god of the sky and the hunt. The multidisciplinary research group includes cardiologists, radiologists, pathologists, geneticists, basic scientists, anthropologists, and archaeologists. “We call ourselves the paleocardiologists,” Dr. Narula says, “just talking about the old or ancient stuff.” Their studies, which have been published in journals like The Lancet and Global Heart, began with a simple question: Is heart disease—atherosclerosis, or the hardening and narrowing of the arteries—a disease of the modern age and industrialization?
The group has now studied more than 100 Egyptian mummies in Cairo and Berlin using a CT scanner and has found that a third of them showed vascular disease up to 3,500 years ago. The hardening of the arteries was identified by the calcium that had deposited in their arteries. Now that kind of throws you off, as to why mankind suffered from heart disease so long ago,” Dr. Narula says. “But then you start finding out about their lifestyles. These mummies were from the elite of Egypt. These are the people who used to be carried on palanquins; there was no exercise for them.” They consumed meat frequently and feasted on bird e.gs; agriculture was well developed, and food was available all day, every day. In essence, the Egyptian elite lived like modern humans—though riding in sedan chairs, not SUVs—and their cardiovascular health paid the toll.
Jagat Narula, MD, PhD, MACC
Next the group studied the mummies of 70 Peruvians from the Andes foothills who were buried 1,000 years ago and had been naturally preserved. “You are now looking at folks who are not sedentary like the Egyptians; 50 percent of them are vegetarians, and 50 percent of them consume leaner meat, such as alpaca.” In this hardy population, the team still found that one-fifth had atherosclerosis. At first, Dr. Narula says, the researchers wondered, “Does that mean we are doomed to have this disease?” But they noticed mummies with black lungs that resulted from long exposure to the smoke of cooking fires. The team made similar observations in five sets of mummified remains in the Aleutian Islands. People in that society kayaked, hunted, and ate fish and meat, but they lived in subterranean households that were warmed with fires and had minimal ventilation through the ceiling, so they were exposed to “indoor pollution.” He maintains that atherosclerosis, today or thousands of years ago, is a result of risk factors.
In their next project, in March, the Horus Group will study mummified remains in Torino, Italy. “During the day we work, and in the evenings and mornings we sit down and discuss the data,” Dr. Narula says. “It’s a very congenial group of about 15 people.” But the mission is a serious one. Dr. Narula sees the study of mummies as a “very convincing” way to promote global cardiovascular wellness and the awareness of risk factors, including cholesterol, smoking, hypertension, diabetes, obesity, and stress. “Mummy research shows us that the risk factors remain the basis for heart disease,” Dr. Narula says. But heart disease is not inevitable: “Prevention or taking care of risk factors should take care of disease.”
From left: Stephen Ellis, Senior Director, Informatics, The Charles Bronfman Institute for Personalized Medicine; Steven Coca, DO; Judy Cho, MD, Ward-Coleman Chair in Translational Genetics, and Director, The Charles Bronfman Institute for Personalized Medicine; and Girish N. Nadkarni, MD.
Clinical researchers in the Division of Nephrology and The Charles Bronfman Institute for Personalized Medicine are leading a new initiative within the Mount Sinai Health System to dramatically accelerate the prescreening process to identify eligible candidates for clinical trials.
The Icahn School of Medicine at Mount Sinai is the first academic institution in the nation to partner with Clinithink, a software developer that has designed a tool known as CLiX ENRICH, a set of algorithms capable of quickly processing large volumes of quantitative and qualitative data from electronic medical records, including physician notes.
Traditionally, researchers spend weeks or months manually sifting through medical records to locate highly eligible patients for potential trial enrollment, a process that increasingly requires submission of qualitative data that can only be extracted through careful analysis of physician notes. “This software ultimately creates customizable lists of patients sorted into tiers, starting from the most eligible patients to least eligible,” says Steven Coca, DO, Associate Professor of Medicine (Nephrology) and executive sponsor of program evaluation.
In a recent proof-of-concept demonstration for an ongoing trial of a drug for patients with diabetic kidney disease, CLiX ENRICH found 97 highly eligible patients in less than three weeks compared with just six patients found over three months using standard methods.
Says Girish N. Nadkarni, MD, Assistant Professor of Medicine (Nephrology) and lead investigator for the CLiX ENRICH evaluation: “Typically, the problem is not enrolling patients quickly enough. Now, our problem is having sufficient number of staff to enroll all of the eligible patients.”
From left: Scott Russo, PhD, with researchers Hossein Aleyasin, MD, PhD, and Caroline Menard, PhD, postdoctoral fellows in the Department of Neuroscience.
A team of researchers at the Icahn School of Medicine at Mount Sinai has conducted a pioneering study of mice behavior and the structure of the brain demonstrating that in some cases, aggressive social interaction— bullying—activates a primary brain reward circuit that makes the activity pleasurable.
The study, led by Scott Russo, PhD, Associate Professor of Neuroscience, appeared in the journal Nature in 2016. Significantly, it was the first time that researchers discovered that specific neural mechanisms between the basal forebrain and lateral habenula mediate the motivation to engage in or avoid this aggressive behavior. Furthermore, they showed that manipulating activity in this circuit alters the activity of brain cells and, ultimately, aggression behavior.
The team used a conventional mouse behavioral model whereby adult mice were placed together with a younger subordinate mouse for three minutes each day for three consecutive days while researchers closely watched their behavior. They determined that with specific conditioning, about 70 percent of mice exhibited aggressive behavior, tending to bully or attack the subordinate mouse, while 30 percent showed no aggression at all. They also observed behavior suggesting that the aggressive mice found the ability to subordinate others rewarding, while the non-aggressive mice developed an aversion to aggression stimuli.
By studying brain activity, the researchers found that the aggressive mice, when given the chance to bully, exhibited increased activity in the basal forebrain neurons that reduce activity in the lateral habenula, an area of the brain that would normally encode an aversion to aggressive stimuli. Conversely, they found that non-aggressive mice exhibited reduced basal forebrain activation and a subsequent increase in lateral habenula neuronal firing, which makes the aggression stimuli aversive.
A scan of tissue from a mouse brain shows an inhibitory neuron (green) in the basal forebrain, which projects directly to the lateral habenula, a circuit that controls aggression.
Researchers then directly manipulated the activity of the neurotransmitter that has a role in this circuit. “When we artificially induced the rapid neuron activation between the basal forebrain and lateral habenula, we watched in real time as the aggressive mice became docile and no longer showed bullying behavior—it was very dramatic,” says Dr. Russo. “Our study is unique in that we took information about the basal forebrain-lateral habenula projections and then actually went back and manipulated these connections within animals to conclusively show that the circuits bi-directionally control aggression behavior.”
Over the years, Dr. Russo says there have been only limited studies on aggression, even though aggression can be a major part of human illness. This research, while promising, is still in its early stages. “It could take 10 years before we have anything ready for testing in humans, but this is a critical first step,” Dr. Russo says. “Targeting shared underlying deficits in motivational circuitry may eventually provide useful information for the development of novel therapeutic drugs for treating aggression-related neuropsychiatric disorders.”
The Mount Sinai research team included investigators from the Fishberg Department of Neuroscience, The Friedman Brain Institute, the Graduate Program in Neuroscience, the Department of Pharmacological Sciences, and the Mount Sinai Institute for Systems Biomedicine.