Children who have older siblings or frequent interaction with grandparents are diagnosed with autism spectrum disorders (ASD) earlier than those who do not, according to new research conducted at the Seaver Autism Center for Research and Treatment at Mount Sinai, and published in the journal Autism.
The study, titled “Grandma Knows Best: Family Structure and Age of Diagnosis of Autism Spectrum Disorder,” found that about 50 percent of friends and family members reported they had suspected a child to have a serious condition before they were aware that either parent was concerned. Maternal grandmothers and teachers were the two most common relationship categories to first raise concerns. “Our work shows the important role that family members and friends can play in the timing of a child’s initial diagnosis of autism,” says Joseph D. Buxbaum, PhD, the G. Harold and Leila Y. Mathers Research Professor, and Professor of Psychiatry, Genetics and Genomic Sciences, and Neuroscience, Icahn School of Medicine at Mount Sinai, and Director of the Seaver Autism Center. He is senior author of the paper, which was published online February 8, 2017. The study included colleagues at Columbia Business School and Carnegie Mellon University.
The team conducted an online survey of 477 parents of children with autism. In addition, they carried out novel, follow-up surveys with 196 “friends and family,” who were referred by parents. Eighty percent of the children with ASD were boys, and the median age of diagnosis was 33 months. Frequent interaction with a grandmother reduced the age of diagnosis by 5.18 months, and frequent interaction with a grandfather reduced the age of diagnosis by 3.78 months. “Since early detection of ASD is critical to effective treatment interventions, we hope the study will serve as a call to action to encourage family and friends to share concerns early on,” Dr. Buxbaum says.
In other news, the Autism Sequencing Consortium, a multi-institute research group founded by Dr. Buxbaum, has received a $7 million extension of a grant from the National Institutes of Health to collect, analyze, and share samples and genetic data from people diagnosed with autism.
The Consortium now includes more than 40 international groups and 150 researchers who have generated gene sequencing data from 29,000 individuals, making it the largest such study to date in autism. All shared data and analyses are hosted on a supercomputer called Minerva, designed by Mount Sinai faculty, which enables joint analysis of largescale data. The new grant will extend the project through 2022 and expand the sample to include more than 50,000 individuals.
Kenneth Teasley, HIV-positive with end-stage renal disease, had been on a waiting list for a kidney transplant for five years. He learned from The Mount Sinai Hospital in the spring of 2016 about his eligibility for an organ from another HIV-positive patient. Mount Sinai was the first hospital in New York State and only the second in the country approved to perform kidney and liver transplants from a deceased HIV-positive donor to an HIV-positive recipient.
Here is his story:
“I was originally diagnosed with HIV in 1993. Then a couple months later, I was diagnosed with CKD at 23 percent,” Kenneth says. “I basically thought I had two years to live.”
CKD or Chronic Kidney Disease is a condition characterized by gradual loss of kidney function over time. Kenneth’s kidneys were functioning at only 23 percent of capacity. After years of suffering, Kenneth began three times a week dialysis treatment sessions.
“It was very hard for me at the beginning. And all you want to do is go to sleep. I was also having issues with my blood pressure,” he says. “I actually fell once, really bad, and that’s actually how they found the stroke that I had earlier that year.”
Kenneth remained on dialysis for five years.
Sander S. Florman, MD: “He’s going to have a much better quality of life, and he’s going to live longer thanks to the gift of organ transplantation.”
“When you’re on dialysis your chances of having a heart attack or a stroke go up dramatically. In fact, most of the people who are on dialysis will die of a heart attack or a stroke,” says Sander S. Florman, MD, Director of The Recanati/Miller Transplantation Institute at Mount Sinai and Charles Miller, MD Professor of Surgery at the Icahn School of Medicine at Mount Sinai. “If you’re lucky enough to get a transplant that risk goes way down.”
Kenneth was placed on the transplant waiting list. But for HIV patients the wait was typically much longer than for those without disease.
“Mount Sinai was a big enroller in an NIH-sponsored trial offering transplants to very carefully selected people with HIV,” says Dr. Florman. “And it turns out, very counter-intuitively, that the medicines that we use for transplant to prevent rejection work synergistically, work right alongside with the medicines that are used to treat HIV. They did well, and this opened the door.”
Kenneth Teasley: “I think I can do anything now. I guess I could be Superman.”
After the surgery, “his kidney function was normal right away and he didn’t have any complications,” says Antonios Arvelakis, MD, MPH, Transplant Surgeon at the Recanati/Miller Transplantation Institute and Assistant Professor of Surgery at the School of Medicine. “Being able to offer an HIV patient the organ of an HIV donor, I’m pretty sure it’s going to help move forward the approach of the treatment for HIV patients.”
Adds Dr. Florman: “He’s going to have a much better quality of life, and he’s going to live longer thanks to the gift of organ transplantation. I couldn’t be more proud of Mount Sinai and of my team’s efforts to offer transplant to HIV because when it comes to transplanting people with HIV there’s a lot of stigma still and a lot of places talk ‘yes’ but very few places do ‘yes.’”
After a week in the hospital, Kenneth returned home.
“I finally realized that I actually can do anything, and it’s not what’s put on you, it’s what you do with it,” he says. “I think I can do anything now. I guess I could be Superman.”
As the Zika virus continues to spread rapidly across the globe, it might pose a particular risk to people previously infected with two related viruses, dengue and West Nile, researchers at the Icahn School of Medicine at Mount Sinai have found. Their study, published in the journal Science, may help explain the severe manifestations of Zika virus infection observed in specific populations, including those in South America.
REVEL developers Weiva Sieh, MD, PhD, left, and Joseph Rothstein, MS
Sequencing-based genetic tests are making personalized medicine a reality for patients who carry certain mutations for serious diseases, including breast and prostate cancer. Armed with information about the pathogenicity of such variants in their genome, these patients can now make proactive decisions about their health care early enough to increase the odds of success in preventing or treating disease.
But for each step forward in this new frontier of personalized medicine, physicians and scientists are stymied by their lack of knowledge about thousands of other rare variants in a patient’s genome that could also portend disease. For this reason, two researchers at the Icahn School of Medicine at Mount Sinai developed REVEL, a novel tool designed to make sense of these variants of unknown importance in order to help guide patient care and risk management and to facilitate research.
Developed by Weiva Sieh, MD, PhD, Associate Professor of Population Health Science and Policy, and Genetics and Genomic Sciences; and Joseph Rothstein, MS, an Instructor of Genetics and Genomic Sciences, and Population Health Science and Policy, REVEL is an acronym for Rare Exome Variant Ensemble Learner. The tool predicts the likelihood of whether a particular coding variant in a person’s genome is disease-causing or benign.
“REVEL is timely and significant because the number of rare variants discovered by sequencing studies is vast and growing and little is known regarding their function,” says Dr. Sieh. “Yet few pathogenicity prediction tools have targeted rare missense variants, leaving researchers and clinicians to struggle with their interpretation.” The ability to distinguish among the approximately 10,000 missense variants in each person’s genome that result in protein changes that could potentially be harmful also helps researchers set priorities for the variants they may wish to study further as new disease-causing genes. Identifying more of these variants would enable personalized medicine to realize its potential in helping more patients benefit from prevention and treatment regimens tailored to their individual disease risks.
Other tools that use different predictive features do exist, but they often do not agree with each other on the likelihood of pathogenicity. Dr. Sieh and Mr. Rothstein created REVEL as an ensemble method that uses machine learning to combine information from many of these other tools in order to generate a consensus score. REVEL incorporates 18 pathogenicity prediction scores from 13 tools, and it specializes in prioritizing the most clinically or functionally relevant variants among the sea of rare variants that are being discovered through next-generation sequencing.
Sandra Masur, PhD, at the podium, congratulated the Jacobi Award recipients, from left: Louis R. DePalo, MD; Celia M. Divino, MD; Ian R. Holzman, MD; Leslie Dubin Kerr, MD; Alice C. Levine, MD; Eric J. Nestler, MD, PhD; and Jonathan S. Stamler, MD.
Seven physicians who have distinguished themselves in medicine or biomedicine, or extraordinary service to The Mount Sinai Hospital, the Icahn School of Medicine at Mount Sinai, or its alumni, were honored with the 2017 Jacobi Medallion—one of Mount Sinai’s highest awards—on Thursday, March 16, at a special event held at The Plaza. Donald Bergman, MD, MSH ’77, President of the Mount Sinai Alumni Association, opened the evening’s events, and Sandra Masur, PhD, Chair of the Jacobi Medallion Award Committee, introduced the recipients.
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, addressed nearly 325 alumni, donors, faculty, and staff at the award ceremony, including Kenneth L. Davis, MD, President and Chief Executive Officer, Mount Sinai Health System, an alumnus of the medical school class of 1973.
“We have invested in the development of intellectual property, patents, and novel partnerships with industry,” Dr. Charney told the audience. “Exciting discoveries have poured forth, including a new understanding of the role of the microbiome in Crohn’s and colitis diseases. We’ve identified genetic risk factors for Alzheimer’s, Parkinson’s, autism, and other mental illnesses, and developed new therapies for multiple myeloma, melanoma, depression, and avian flu, to name just a few.” These advances, he said, were a tribute to the generosity and support of Mount Sinai’s alumni and to the dedicated educators who carry out “Mount Sinai’s longstanding tradition of excellence.”
The honorees are:
Louis R. DePalo, MD, MSH ’85, Sarah and Eric Lane Professor of Pulmonary Medicine, Clinical Director, Mount Sinai-National Jewish Health Respiratory Institute
Dr. DePalo is an expert in pulmonary, critical care, and sleep medicine. His research interests include the study of human airway smooth muscle cell function, sarcoidosis, and advanced lung diseases. He has published important articles in peer-reviewed journals and has received numerous grants, American Lung Association research awards, and a National Institutes of Health career development award. Dr. DePalo is highly experienced in implementing new technology for use in medical education, patient care, and the distribution of information throughout the medical community.
Celia M. Divino, MD, MSH ’97, Stanley Edelman, MD Professor of Surgery, Chief, Division of General Surgery, Vice Chair for Education and Quality, Program Director, General Surgery Training Program
A surgical educator, leader, and innovator, Dr. Divino has extensive experience in advanced minimally invasive techniques. She established Mount Sinai’s Surgical Simulator Center to help residents hone their technical skills in both minimally invasive and traditional procedures. Dr. Divino has been listed among the “Best Doctors in America” and has been included in New York magazine’s Top Doctors list since 2014. Within the Mount Sinai Health System, Dr. Divino maintains oversight of the Quality Assurance, Surgical Education, and Performance Improvement Committees, and the American College of Surgeons National Surgical Quality Improvement Program.
Ian R. Holzman, MD, Professor of Pediatrics, Division of Newborn Medicine, Jack and Lucy Clark Department of Pediatrics, Professor, Department of Obstetrics, Gynecology and Reproductive Science
Under Dr. Holzman’s leadership, the Jo Carole and Ronald S. Lauder Newborn Intensive Care Unit in The Mount Sinai Hospital opened in the spring of 2016, following a complete renovation and expansion. Dr. Holzman, who serves as the Pediatric Vice Chair for Hospital Operations and Faculty Affairs, has also been Chair of the Hospital’s ethics committee for more than 20 years. The author of more than 120 scientific articles and 36 book chapters, Dr. Holzman’s research has included studies of fetal intestinal oxygen consumption and the physiological responses to hypoxemia and anemia in both fetal and neonatal lambs. He has lectured nationally and internationally, most recently on various topics in bioethics. Dr. Holzman has received the Dean’s Award for Excellence in Clinical Medicine, the Alexander Richman Award for Humanism in Medicine, and multiple attending physician and teaching awards from both physicians and nurses.
Leslie Dubin Kerr, MD, MSH ’85, Professor of Medicine, and Geriatrics, Division of Rheumatology
Dr. Kerr leads clinical and educational programs in rheumatology for the departments of Medicine and Geriatrics. For 18 years, she served as Assistant Director and then Program Director of the Rheumatology Program Fellowship. After perceiving there was an unmet need in the rheumatologic care of the elderly, Dr. Kerr developed the geriatric rheumatology practice for the multidisciplinary Phyllis and Lee Coffey Geriatrics Practice at the Martha Stewart Center for Living. Upon completing her internship and residency at Mount Sinai, Dr. Kerr received the Association of the Attending Staff/Bella Trachtenberg Award for House Staff Excellence. She completed her rheumatology fellowship at Mount Sinai under the mentorship of Harry Spiera, MD.
Alice C. Levine, MD, MSH ’86, Professor of Medicine, Division of Endocrinology, Diabetes, and Bone Disease, Professor, Department of Oncological Sciences
Cited as one of America’s Top Doctors® by Castle Connolly and by Super Doctors® in New York, Dr. Levine focuses on patients with diseases of the adrenal, pituitary, and reproductive glands. She is co-director of a translational prostate cancer research lab, which has received grants from the U.S. Department of Defense, the T.J. Martell Foundation, the Prostate Cancer Foundation, and Prostate Action, Inc. In addition, Dr. Levine has published extensively in peer-reviewed journals and is a highly sought-after speaker in the field of prostatic and adrenal diseases. As one of Mount Sinai’s most respected teachers, Dr. Levine in 2011 received an Excellence in Teaching Award from the Icahn School of Medicine at Mount Sinai’s Institute for Medical Education. She has also received the Cullman Family Award for Excellence in Physician Communication.
Eric J. Nestler, MD, PhD, Nash Family Professor of Neuroscience, Director, The Friedman Brain Institute, Dean for Academic and Scientific Affairs
The goal of Dr. Nestler’s research is to better understand the molecular mechanisms of addiction and depression based on work in animal models, and to use this information to develop improved treatments for these disorders. A prolific investigator, Dr. Nestler has published more than 450 peer-reviewed studies and book chapters, and is active in numerous research projects that are funded by the National Institute on Drug Abuse and the National Institute of Mental Health. Dr. Nestler is a member of the National Academy of Medicine (formerly Institute of Medicine) and a Fellow of the American Academy of Arts and Sciences. He is a past President of the American College of Neuropsychopharmacology and current President of the Society for Neuroscience.
Jonathan S. Stamler, MD, MSSM ’85, President, Harrington Discovery Institute, Robert S. and Sylvia K. Reitman Family Foundation
Distinguished Chair in Cardiovascular Innovation, Professor of Medicine and of Biochemistry,Director, Institute for Transformative Molecular Medicine, Case Western Reserve University,University Hospitals Cleveland Medical Center
A Mount Sinai alumnus, Dr. Stamler is recognized for broadly influencing the biological sciences by discovering protein S-nitrosylation, a fundamental mechanism for controlling protein function, and for advancing the understanding of cellular signaling by small gaseous messengers. He has published more than 300 scientific papers and chapters, edited two books, authored more than 125 patents and patent applications, and cofounded multiple companies. After receiving his medical degree at Mount Sinai, Dr. Stamler completed his internship,residency, and fellowships in both Cardiovascular and Pulmonary Medicine at Harvard Medical School and Brigham and Women’s Hospital. Before joining Case Western Reserve School of Medicine, he held faculty positions at Harvard Medical School, Duke University School of Medicine, and the Howard Hughes Medical Institute.
From left: Barbara Davis, Chief Operating Officer of The Actors Fund; Brian Stokes Mitchell; and Lisa Mazie, Chief Administrative Officer of Mount Sinai West.
Mount Sinai Doctors and The Actors Fund recently opened The Samuel J. Friedman Health Center for the Performing Arts, a medical facility in a very “Broadway” location—upstairs from the Actors Fund headquarters at 729 Seventh Avenue and up the street from the Times Square TKTS booths.
The Center is open to the general public, but its services and flexible hours are targeted to people in entertainment and the performing arts. Staffed by Mount Sinai physicians, it offers primary care services, including wellness checkups, urgent sick visits, and health screenings, and is planning to add specialty services in fields like orthopedics and otolaryngology later this year. “This really is a collaboration; it’s like putting on a show,” the actor Brian Stokes Mitchell, Chairman of the Board of Trustees of the Actors Fund, said at the ribbon-cutting ceremony on Thursday, March 2.
Partly funded by a $1 million donation from the Gerald J. and Dorothy R. Friedman New York Foundation for Medical Research, the Center is a project special to the Friedman family, which has deep ties to both medicine and the arts. It is named for the late Samuel J. Friedman, a publicist who worked with performers Bette Davis and Gypsy Rose Lee—and who was the brother of the late Gerald J. Friedman, MD, founder of the Diabetes Institute at Mount Sinai Beth Israel that bears his name.
“Mount Sinai has a long history of providing primary and specialty care for the performing arts community, and we are proud to continue that legacy in our partnership with The Actors Fund,” says Evan L. Flatow, MD, President of Mount Sinai West.
As the Zika virus continues to spread rapidly across the globe, it might pose a particular risk to people previously infected with two related viruses, dengue and West Nile, researchers at the Icahn School of Medicine at Mount Sinai have found. Their study, published in the journal Science, may help explain the severe manifestations of Zika virus infection observed in specific populations, including those in South America.
